Urology

John Young, Professor of Physiology, former Dean of Medicine and Pro-Vice Chancellor at the University of Sydney, died on 10 February 2004 of acute myeloid leukaemia. He was an exceptional scientist and a humanist with a passionate and informed interest in classical culture, Reformation theology and music. John was born on 18 April 1936 in Brisbane. He graduated from the University of Queensland with a BSc (Hons I) in pathology in 1956 and with an MB BS (Hons I) in 1960, earning the University Medal. In 1962, after an internship at Royal Brisbane Hospital, John joined the Kanematsu Memorial Institute in Sydney, where his studies on renal amino acid transport earned him an MD from the University of Queensland (1965) and a C J Martin Fellowship from the National Health and Medical Research Council. He then joined Professor Karl Ullrich at the Physiologisches Institut of the Free University in Berlin. It was Ullrich who persuaded him to work on salivary physiology, the field that John was to dominate until his death. John took up a Senior Lectureship in Physiology at the University of Sydney in late 1966, rising to become Professor of Physiology in 1976. His contributions to science were recognised by the award of a DSc from the University of Queensland (1975) and the Research Professorship of the Alexander von Humboldt Stiftung (1998). He was elected to Fellowship of the Royal Australasian College of Physicians (1976) and of the Australian Academy of Sciences (1986), in which he served as Vice President and Secretary (Biological). After he became Dean of Medicine at the University of Sydney in 1989, he oversaw the introduction of the 4-year graduate program, the development of independent clinical schools, and the foundation of the Clinical School at Canberra. Between 1994 and his retirement in 2003, he was Pro-Vice Chancellor (Health Sciences). Although he was active on many boards, including those of the Central Sydney Area Health Service and the Children’s Hospital at Westmead, he was particularly proud of his role in fostering the Menzies School of Health Research (in Darwin) and (in Sydney) the Kolling Institute at the Royal North Shore Hospital and the Anzac Institute at Concord Hospital. John was always active outside his own profession. He co-edited the University of Sydney’s Centenary book of the Faculty of Medicine and worked unstintingly for the Australian Physiological and Pharmacological Society and for Musica Viva. He also found time to write several biographies on important figures in Australian medicine for the Australian dictionary of biography. Most importantly, his passion for classical art and archaeology led him to play key roles in the University of Sydney’s Nicholson Museum concerts and in the creation and development of the Australian Institute of Archaeology at Athens. David I Cook

David I Cook

A 53-year-old Asian man with type 2 diabetes mellitus presented to the Emergency Department with acute onset of generalised muscle cramps. He reported a 2-month history of polydipsia, polyuria and passing “milky” urine with blood clots. He had travelled widely throughout subtropical Asia. On examination, he was normotensive, with no lymphadenopathy, abdominal masses or oedema. Urinalysis showed marked proteinuria, glycosuria and haematuria. The urine protein excretion rate was later confirmed to be 15.57 g/24 h (reference interval [RI], 0.02–0.15 g/24 h). Urine triglyceride measurement and lipoprotein electrophoresis confirmed the appearance of chylomicrons in the urine after an oral fat tolerance test (Box 1). Biochemical analysis of serum showed the following levels: sodium 121 mmol/L (RI, 134–146 mmol/L), potassium 4.6 mmol/L (RI, 3.4–5.3 mmol/L), creatinine 46 μmol/L (RI, 60–105 μmol/L), glucose 19.7 mmol/L (RI, < 5.5 mmol/L), ferritin 16 mg/L (RI, 30–620 mg/L), 25-hydroxyvitamin D 11 nmol/L (RI, > 50 nmol/L), total cholesterol 5.2 mmol/L (RI, <5.5 mmol/L), and triglyceride 1.8 mmol/L (RI, < 1.8 mmol/L). The patient had marked hypoproteinaemia and hypoalbuminaemia, with a total protein level of 39 g/L (RI, 63–80 g/L) and albumin level of 21 g/L (RI, 35–50 g/L), respectively. The serum IgE level was also raised (2300 kU/L; RI, < 210 kU/L). The patient was mildly anaemic (haemoglobin level, 120 g/L [RI, 130–170 g/L]), with a normal erythrocyte sedimentation rate and C-reactive protein level. There was lymphopenia but no eosinophilia. No microfilariae or acid-fast bacilli were detected in thick blood films taken at midnight or in a urine sample. Serological and intradermal tests for filariae were also negative. A chest x-ray and computed tomography scan of the abdomen and pelvis were normal. A biopsy of the right kidney showed evidence of mild mesangial change, consistent with diabetes mellitus. Lymphoscintigraphy showed delayed lymphatic transport, particularly on the left side, but no physical obstruction to lymphatic drainage. Contrast lymphangiography demonstrated a grossly abnormal lymphatic system in the pelvis and groin with a unilateral left-sided lymphorenal communication (Box 2). A presumptive diagnosis of filariasis was made and the communication between the left kidney and the lymphatics was surgically disconnected. The chyluria recurred after surgery, but within 4 weeks of a therapeutic course of the antifilarial diethylcarbamazine there was complete resolution. Furthermore, the biochemical abnormalities reversed, consistent with urinary loss as the mechanism. At 3-year follow-up, the patient remained symptom-free and without chyluria. DiscussionChyluria is rare in Australia but common in many parts of the world, particularly where Wuchereria bancrofti, the main agent of filariasis, is endemic. It occurs, on average, 5–10 years after the worm has died, and so there may be no evidence of active filariasis. However, a therapeutic trial of diethylcarbamazine should be considered before undertaking surgery. As spontaneous remissions of chyluria have been reported, we can not be certain whether the antifilarial therapy was responsible for resolution of the chyluria in this case. 1: Oral fat tolerance test Urine of patient before a 75 g oral fat tolerance test (0 h) and at serial time points (0.5, 1, 2, 3, 4, and 5 h) after the test. 2: Contrast lymphangiography Contrast lymphangiogram, showing a grossly abnormal lymphatic system with a unilateral left-sided lymphorenal communication (arrow).

John R Burnett MB ChB, FRCPA, PhD · Gary G Sturdy MB BS · Suzzanne J Smith BSc(Hons) · Yuli Ten MB BS · Michael J McComish MB BS, FRACP

In reply: The fundamental purpose of clinical practice guidelines is to improve patient outcomes. Thus, as members of the CARI (Caring for Australians with Renal Insufficiency) Guidelines Steering Committee, we welcome Johnson's letter, which gives us reassurance and renewed enthusiasm to move forward with improving and refining the CARI clinical practice guideline process. The most gratifying revelation in Johnson's survey was the near-90% endorsement of the CARI guidelines as a document providing a useful evidence summary — clearly very reassuring in those areas in which that evidence relates to treatment interventions for patients with renal disease. Of additional interest was the range of responses to questions about matching the recommendations with available evidence. This seems to reflect both an awareness among renal medicine health workers of the importance of evidence-based medicine and a maturing understanding of the need for the evidence to be of high quality. The CARI guideline process has a relatively short history (just over three years), and before Johnson's survey the CARI Steering Committee had adopted a number of strategies that anticipated some of the issues his survey raises. These strategies included: establishing a formal link with the Renal Cochrane Organisation (to produce the best possible search outcomes of all the available evidence); adopting the National Health and Medical Research Council (NHMRC) evidence levels I (systematic reviews) and II (randomised controlled trials) as the minimum requirement to justify definitive guidelines (to assess the quality of evidence available and match appropriate guidelines with that evidence); adopting a peer-review process to evaluate draft guidelines to complement newly revised requirements for guideline writers' conflict-of-interest declarations (to assess perceptions of guideline validity and the influence of external agencies); broadening the multidisciplinary nature of guideline working parties. In addition, the Australian Kidney Foundation has moved to further disseminate the guidelines, and the CARI guideline process has been reformed with the aim of meeting the standards required to achieve NHMRC endorsement. Furthermore, feedback obtained from legal advisers suggests that the CARI guidelines and the process of establishing them are far more likely to obviate litigation than to promote it. The next important phase for the CARI guidelines will be the development of an implementation process. As the acceptance of evidence-based medicine increases and the knowledge base among healthcare workers of the nature, quality and relevance of evidence in patient care expands, the CARI guideline process is likely to be enhanced. The results of future surveys of the type carried out by Johnson will be keenly anticipated.

Rowan G Walker

To the Editor: A 63-year-old woman presented with polyuria, polydipsia, lethargy and vomiting. Two weeks previously, she had been diagnosed as having diffuse scleroderma with possible interstitial lung disease, and had started taking 50 mg prednisolone daily. Her past history included diabetes, hypertension, hypercholesterolaemia and β-thalassemia trait, and her other medications were metformin, glibenclamide, quinapril and amlodipine. Examination revealed blood pressure 150/60 mmHg, a loud second heart sound with no murmurs, and late inspiratory crepitations at lung bases. Her serum creatinine concentration was 270 μmol/L (compared with 100 μmol/L two weeks previously) and serum glucose concentration was 26.5 mmol/L. Treatment by the admitting doctor included insulin, rehydration, and cessation of prednisolone (given hyperglycaemia) and quinapril (secondary to acute renal impairment). She developed a fever and cough, with bilateral pneumonia, which was treated with intravenous ceftriaxone. Despite normotension, concern regarding scleroderma renal crisis (SRC) was raised. On Day 12 of admission, when renal failure had developed to the dialysis-dependent level (serum creatinine level, 690 μmol/L), quinapril was recommenced for its proposed renoprotective effect and haemodialysis was initiated. Microangiopathic haemolytic anaemia (haemoglobin, 7.2 g/L) was diagnosed, with fragmented red blood cells (Box). Several months later, she continues on haemodialysis three times a week. Renal biopsy was not performed given the clinical picture of diffuse scleroderma and recent corticosteroid use with rapid development of renal failure — consistent with SRC. SRC is defined as rapidly progressive renal failure and/or new onset of malignant hypertension during the course of scleroderma, occurring in 15%–20% of patients with the diffuse variety.1 Risk factors include male sex, black race, and early diffuse scleroderma with rapidly progressive skin thickening.2 Precipitation of SRC by corticosteroid use, especially in normotensive patients, is well described, particularly with high-dose (>15 mg/day) treatment.2 Early diagnosis is critical because treatment may preserve renal function.3 Outcomes have improved with use of angiotensin-converting enzyme (ACE) inhibitors,2 which are thought to improve renal function by controlling the high renin levels seen in patients with SRC. About 61% of patients have a good outcome, with no or temporary dialysis.3 Predictors of poor outcome, despite ACE inhibitor use, include older age, male sex, higher initial serum creatinine level, and scleroderma myocardial disease.1 Eleven per cent of SRC patients remain normotensive and have significantly reduced 12-month survival rates.4 This may relate to delay in diagnosis of SRC. The use of high dose corticosteroids in patients with early diffuse scleroderma should be strongly discouraged, and intensive monitoring for SRC is recommended if low dose corticosteroids are required. Peripheral blood film, magnification x40 Changes of thalassaemia (microcytosis and hypochromasia) and microangiopathic haemolysis (fragmented red cells and spherocytes). 1. Spherocytes. 2. Fragmented red blood cells.

Anita T Y Lee · Simon Burnet

Objective: To investigate whether late referral to a nephrologist of patients with chronic renal insufficiency influences the likelihood of both transplantation and mortality among those who survive at least one year on dialysis.Design: Retrospective national cohort study, using data from the Australia and New Zealand Dialysis and Transplant Registry database.Participants: All patients with end-stage renal disease who started renal replacement treatment in Australia between 1 April 1995 and 31 December 1998, excluding those who received transplants or who died in their first year of dialysis. Patients referred "late" were defined as those who needed to commence dialysis within three months of referral to a nephrologist.Main outcome measures: Length of patient survival, and whether patients received a transplant at any time between one year after starting dialysis and completion of the study on 31 March 2000.Results: Of the 4243 patients included in the study, 1141 (26.9%) were referred late. Late-referral (LR) patients were significantly less likely to receive a transplant in their second and subsequent years on dialysis (adjusted rate ratio, 0.78; 95% CI, 0.64–0.95). LR patients were at significantly increased risk of death after their first year on dialysis (adjusted hazard ratio, 1.19; 95% CI, 1.04–1.35).Conclusions: Late referral is associated with increased mortality, even among those who survive their first year on dialysis. Improving the quality of pre-dialysis care might improve access to transplantation and long-term survival. General practitioners could minimise late referrals through targeted screening of high-risk individuals.

Alan Cass FRACP · Joan Cunningham ScD · Zhiqiang-Wang PhD · Wendy Hoy FRACP · Peter C Arnold MB BCh · Paul Snelling FRACP

In 2000, chronic or unspecified renal failure was listed as a cause of death of 9160 Australians (7.1% of all deaths) (source: Australian Bureau of Statistics, special data request, 2002). Most would have had chronic renal impairment (CRI) for years. Each year, more than 1700 people with end-stage renal disease (ESRD) start dialysis or receive a transplant.1 These figures suggest that the impact of CRI is substantial and that in order to prevent progression to ESRD we need to develop systems for its detection and management. Prevalence and significance of proteinuria. The Australian Diabetes, Obesity and Lifestyle (AusDiab) Study,2 a cross-sectional survey of a sample of over 11 000 Australians aged 25 and over, found proteinuria in 2.5% of the study population and a serum creatinine level above 120 µmol/L (reference range, 50–110 µmol/L [adult women], 60–120 µmol/L [adult men]) in 1.1%. A recent US study estimated that 1.5% of people aged six years and over have proteinuria.3 Extrapolating from these data, it is likely that several hundred thousand Australians have proteinuria, which is associated with a 15-fold increased risk of developing ESRD within 10 years.4 Whose urine should be screened? Current evidence does not support universal screening for proteinuria. The US Multiple Risk Factor Intervention Trial,5 in which more than 300 000 men were screened and followed up for an average of 16 years, showed that older age, smoking, hypertension and diabetes were significant risk factors for ESRD. Familial aggregation of ESRD, in excess of that predicted by clustering of diabetes and hypertension, has also been demonstrated.6 Indigenous Australians, who make up less than 2% of our population, comprise more than 8% of ESRD patients;1 and, in some remote communities where screening has been conducted, almost 25% of adults have been found to have proteinuria.7 Specific groups of people known to be at increased risk of ESRD should therefore be targeted for screening (see Box 1). Dipstick testing is cheap (about $0.50 per test), with immediate results. More than a trace of protein indicates a protein excretion rate greater than 300 mg in 24 hours. In the AusDiab study,2 dipstick testing had about 85% sensitivity and specificity (S Chadban, Nephrologist, AusDiab Steering Committee, personal communication). As about 15% of people without proteinuria have a falsely positive result, people with a positive dipstick result should have their protein excretion rate quantified by further testing. Measurement of 24-hour urinary protein excretion rate has long been the gold standard, but reliable collection is often impractical. Measurement of the albumin–creatinine ratio (ACR) in a morning urine specimen is easier and sufficiently precise.9 An ACR over 34 g/mol indicates a daily protein excretion rate exceeding 300 mg. At the same time as measuring the urinary ACR, a blood sample should be sent for measurement of serum creatinine and electrolyte levels for further assessment of renal function. Most dipsticks also test the urine for substances other than protein. If leukocytes or nitrites are detected, especially with symptoms suggestive of a urinary tract infection, a midstream urine specimen should be cultured. The dipstick test for proteinuria should be repeated after treatment of any infection. Isolated haematuria rarely indicates glomerular pathology associated with progressive renal disease. However, among smokers and people screened on the basis of age, a finding of haematuria should prompt exclusion of urinary tract malignancy. Interpreting the serum creatinine level. Serum creatinine level per se is not an accurate indicator of renal function. The glomerular filtration rate (GFR), which can be estimated from the serum creatinine level, is the most meaningful single measure (see Box 2). In healthy adults, the GFR exceeds 80 mL/min; patients with a GFR between 30 and 80 mL/min have CRI; while a GFR below 30 mL/min indicates severe renal impairment with a high risk of progression to ESRD, warranting prompt referral to a nephrologist. Managing CRI in general practice. General practitioners can substantially reduce the risk of progression of renal impairment. Management guidelines developed by the Australian Kidney Foundation and the Australia and New Zealand Society of Nephrology are accessible at the "Caring for Australians with Renal Impairment" website.11 I discuss here the evidence for the interventions recommended in the guidelines. Further benefit may be obtained by reducing the high risk of cardiovascular events that accompanies renal disease.12 Intensive control of hyperglycaemia and hypertension is beneficial for people with diabetes. (Specific interventions for diabetes are beyond the scope of this article — see the guidelines of the Australian Diabetes Society.8) In all patients with CRI, management aims should be the reduction of proteinuria (to ACR < 100 g/mol) and the maintenance of renal function (ie, stable GFR). These can be achieved through intensive control of hypertension11 (Level I evidence13). Suggested blood-pressure targets are 125/75 mmHg (in people under 50 years) and 135/85 mmHg (in people ≥ 50 years). Multidrug therapy is usually required. Angiotensin-converting enzyme inhibitors and angiotensin-II-receptor antagonists have been shown to be renoprotective (Level I and Level II evidence, respectively).11 Even in the absence of hypertension, they may be effective in people with protein excretion exceeding 1 g/day (ie, an ACR above 100 g/mol). Treatment for this normotensive group should be adjusted according to the level of proteinuria and monitored with three- to six-monthly ACR estimates. Potential risks include hyperkalaemia and, in patients with renal artery stenosis, worsening of renal impairment. In randomised controlled trials of these agents, participant dropout rates due to adverse effects have been low. Because smoking is associated with increased risk of progression of renal impairment (Level III-2 evidence),11 smokers should be assisted to quit smoking. A low-protein diet is not recommended, as the benefit is minimal and malnutrition may ensue. There is little evidence regarding the impact of exercise; however, in view of its cardiorespiratory benefits, regular exercise is advised. There is currently insufficient evidence to warrant lipid-lowering therapy as a means of minimising progression. Who should be referred to a nephrologist? GPs can usually manage patients with CRI, preventing further renal damage and progression to renal failure. Indications for prompt referral to a nephrologist include estimated GFR below 30 mL/min; estimated GFR above 30 mL/min, but declining rapidly; age less than 35; ACR greater than 300 g/mol (nephrotic range for proteinuria); symptoms or signs suggestive of systemic illness (eg, systemic lupus erythematosus); or failure to reach blood pressure or ACR targets within six months of starting antihypertensive drug therapy. 1: Indications for annual dipstick testing for proteinuria Age over 50 Hypertension Smoking Diabetes* Family history of renal disease Aboriginal or Torres Strait Islander descent *People with diabetes also require annual testing for microalbuminuria. (See the Australian Diabetes Society position statement on microalbuminuria in diabetes.8) 2: Calculation of glomerular filtration rate (GFR) by the modified Cockcroft–Gault formula*10 For women Estimated GFR (in mL/min)† = 140 – age (in years)] x weight (in kg) serum creatinine level (in µmol/L) For men Calculate estimated GFR as for women, then multiply by 1.23. * The modification is an arithmetic simplification of the original formula. The GFR estimate obtained will be 4% lower for women, and unchanged for men, compared with an estimate obtained using the original formula. † A number of computerised clinical record systems include a calculator for this formula.

Alan Cass MB BS, FRACP, GradDipClinEpid

Objective: To compare hospital costs of Aboriginal and non-Aboriginal patients having haemodialysis treatment and forecast the future treatment cost.Methods: The costs of patients with HD in the "Top End" of Australia's Northern Territory were estimated for the financial years 1996/97 and 1997/98 using a hospital costing model. We used an Autoregression Integrated Moving Average model to predict future demand.Results: 165 patients (101 Aboriginal and 64 non-Aboriginal) were treated at a total cost of $12.4 million in this two-year period. These 165 patients represented 0.7% of inpatients, 8.8% of total inpatient costs and 31.6% of total inpatient episodes of care in the Top End region. $9.5 million (77%) was spent on routine haemodialysis treatment and $2.9m (23%) on other hospitalisations. The average cost per routine haemodialysis treatment over the two-year period was $527, or $78 600 per patient treatment year. Hospitalisations for comorbidities occurred in 86% of Aboriginal and 39% of non-Aboriginal patients. Average cost per patient, number of admissions and length of hospital stays were all significantly greater for Aboriginals. We predict an average increase in the number of treatments of 12% each year over the next five years and a five-year cost of $49.8m.Conclusions: A multipronged strategy designed to reduce the prevalence and costs of renal failure is required.

Jiqiong You MSc, MBA, MB BSc · Yuejen Zhao PhD · Carol Beaver MSc · Wendy Hoy FRACP · Kathy Eagar PhD

Disorders of the kidney and related disturbances are being explored at the cellular and molecular level, and advances are moving apace. Hypertension and the kidney. Kidney disease and high blood pressure are closely linked. Hypertension is multifactorial in origin and not previously considered a single gene disorder. However, although most people with high blood pressure do not have kidney disease, there have now been at least six single gene mutations linked to families with hypertension, all at sites of renal tubular proteins responsible for salt and water balance.1 These genotype studies both lead us to novel causes of hypertension, and provide a potent source of likely targets for treating hypertension. Delineation of the structures of salt transporters in the renal tubules, their alteration and genetic control has created an environment that suggests gene insertion and alteration may be possible and may be applicable to a variety of inherited renal transport disorders. Gene manipulation in such disorders as nephrogenic diabetes insipidus should not be far away. A wide range of genetic abnormalities have been identified in these rare familial salt-handling disorders, and they can be easily identified in babies within days of birth. Whether "salt-sensitive" hypertensive people who respond to salt restriction will be able to have their salt balance altered by genetic manipulation of the renal tubule remains unclear. Patients with high blood pressure and proteinuria have a poor prognosis. Recent observations in such individuals have shown that the use of angiotensin-converting enzyme inhibitors and blocking agents not only controls blood pressure, but reduces proteinuria and improves prognosis by slowing the progression of the vascular dysfunction.2 This is true in patients with diabetes and extends to patients with hypertension but no diabetes. In acute (but reversible) toxaemia of pregnancy, studies are now unlocking the process that elevates blood pressure and damages the kidney (usually reversibly). Understanding this process, which involves vasoactive factors and the interleukins, will lead to a new approach to managing high blood pressure. The interrelationship between these vascular and immune reactive proteins has wider application in looking at the antecedents of "essential hypertension" and deciphering the reasons for end-organ (renal) damage. Autosomal-dominant polycystic kidney disease (ADPKD). This disorder is responsible for 15%–20% of people on dialysis. Recent studies have recognised that people with ADPKD have normal kidneys at birth, and that the cysts develop later. ADPKD is being viewed as a neoplasm in disguise, so that expanding therapies for malignancy may affect the development of the cysts by reducing the rate of mutations. At the same time, recognition of the abnormal polycystins that may interfere with cell–cell interactions could provide a target for future interventions. Growth-factor tyrosine-kinase inhibitors are now entering trials in the management of malignancy that may be applicable in ADPKD. Glomerulonephritis. There have been few developments in the understanding or management of most causes of glomerulonephritis. Poststreptococcal glomerulonephritis persists only in disadvantaged communities with poor access to medical care. IgA nephropathy, probably the commonest cause of glomerulonephritis in our community, remains largely a mystery. There is increasing evidence that the IgA is abnormal in its chemical and spatial structure, and that its deposition triggers the inflammatory response.3 In the future, this may allow us to target the precipitant and prevent the disease. Renal transplantation: allografts and xenografts. Organ replacement is the ideal management strategem for organ failure. Unfortunately, organ availability does not meet demand, and, even in successful transplants, chronic rejection remains a long term problem. The first issue has been approached by encouraging more family and unrelated "friends" to consider donations. The ethics of paying donors remain unresolved, especially in countries where payment provides a significant financial "win" for donors. It is illegal to pay for organs in Australia. An alternative is xenografting, and an increasing understanding of the process of hyperacute rejection and the ability to manipulate the antigenicity of the donor tissue opens the way for "designer" organs.4 Xenografts may be possible in the next decade. Potential problems such as unknown infective agents, longevity of grafts related to the natural life of the animal donor, different physiological and pharmacological responses do not seem overwhelming in the short term — if organs can be manufactured for specific recipients then replacements may be possible with little problem. Chronic rejection is also a major problem for successful allografts. Understanding the process of tolerance that occurs in some individuals should unlock this process and make possible treatments to facilitate tolerance. The two areas of xenografting and tolerance induction and maintenance will be closely linked and should see increased organ availability and longevity.

David J Tiller AO, MB BS, FRACP · Annemarie Hennessy PhD, MB BS FRACP

Editorial Holistic care in hospital patients Patients who require long-term, frequent specialty care may have their primary healthcare needs ignored MJA 2001; 175: 292-293 In this issue of the Journal, Jang and colleagues highlight an apparent neglect of women's health issues in a cohort of women undergoing regular haemodialysis in Victoria.1Their cross-sectional survey of 48 women undergoing haemodialysis in hospitals or satellite dialysis centres contributes to the scarce literature on reproductive health issues in women with end-stage renal disease (ESRD). It also clearly illustrates the potential for holistic care to be neglected when patients are managed in a highly specialised environment. The most startling finding of the study is the poor adherence to accepted guidelines for cervical cancer screening and mammography: 55% of patients had not had cervical screening within the previous two years, while 38% of those aged 50 years or over had not had mammography within the same period. These findings are echoed in a recent report on women undergoing haemodialysis in the United States.2 The figures compare with contemporary Australian screening adherence rates of 64% for cervical screening (women aged 20-69 years)3 and 54% for mammography (women aged 50-69 years).4 Thus, despite intense contact of dialysis patients with the healthcare system, adherence to screening is lower than in the general population. Results from the survey also indicate the need to improve sexual counselling, contraceptive advice, menopausal management and fracture prevention among these women. . . . why are nephrologists, or indeed other hospital-based specialists, not currently dealing with patients' global health issues? . . . Consideration of hormone replacement therapy (HRT) and osteoporosis treatment is difficult in women with ESRD. As the authors outline, HRT carries a potential risk of vascular access thrombosis, and there are currently no evidence-based data on the risk-benefit ratio in this group.5 Treating or preventing bone disease in ESRD is complex, and currently limited by lack of efficacy and side effects of the common therapeutic agents and lack of data on agents such as bisphosphonates. Nevertheless, it is surprising that few of the 11 postmenopausal patients with fractures could recall HRT being discussed with them, and only one was taking this therapy. An important question raised by this survey is "Who should be responsible for general healthcare issues in these patients?". The report does not say how many respondents claimed to have a general practitioner (GP) and, if so, maintained regular contact with this GP. However, a reason usually given by dialysis patients for not attending a GP is that they already spend many hours at the hospital or dialysis centre (usually about four hours, three times a week) and, not unreasonably, expect all their health issues to be dealt with during that contact. Jang and colleagues conclude from their survey that hospital-based dialysis services should include a service that deals with women's health issues to ensure that this aspect of their routine health management is not neglected. So, why are nephrologists, or indeed other hospital-based specialists, not currently dealing with patients' global health issues? Clearly, specialists are generally aware of guidelines for women's health screening. However, it is not a major daily focus of the already complicated care of their patients and is more likely to be overlooked by a physician focusing on time-consuming, dialysis-related problems. The burgeoning number of dialysis patients combines with limited funding to compound this problem. In view of these real-life pressures, I suggest an alternative approach that involves patients' GPs, whose daily practice already encompasses women's health screening. Since 1995, the Renal Unit at the Princess Alexandra Hospital, Brisbane, has implemented a "Renal Care and Support Program" to consolidate links between GPs and dialysis and transplant centres. Interaction is via a booklet which contains a summary of the patient's active and past problems, status of their health screening checks (such as those raised by Jang and colleagues), list of medications, information pages and key guidelines for care of the ESRD patient. Advances in information technology continue to enhance these lines of communication. Many studies have shown that integrated management involving GPs achieves outcomes similar to, and in some instances better than, hospital care.6 Our program aims to address the global health issues of patients.7In comparison, the model proposed by Jang seems limited. It would underutilise the skills of primary care physicians in healthcare screening, duplicate services available in general practice, and move these aspects of patient care to a system and staff not resourced to deal with them. However, if GPs are to be significantly involved in the care of patients with ESRD, we must consider the suitability of applying general principles of care to these patients. This, I believe, can be achieved by providing guidelines in specific areas where approaches differ. For example, it is reasonable to exercise caution in administering HRT to a patient with recurrent vascular-access thrombosis, and some women with ESRD have such a poor prognosis that applying general population guidelines is not appropriate. This issue has not been addressed by Jang and colleagues. The findings of Jang's study illuminate an increasing problem in our contemporary healthcare system: patients who have frequent contact with subspecialty care may have primary healthcare issues ignored. One way of addressing this issue is a hospital-based service to deal with women's health issues, as proposed by Jang and colleagues, while an alternative is shared care between the specialist service and GPs. Clearly, further consideration and research is required. The issues raised are also likely to translate to subspecialty services other than nephrology. Carmel M Hawley Director of Nephrology Princess Alexandra Hospital, Brisbane, QLD carmel_hawleyAThealth.qld.gov.au Jang C, Bell RJ, White VS, et al. Women's health issues in haemodialysis patients. Med J Aust 2001; 175: 298-301. Rush H, Neugarten J, Coco M. Women's health issues in a dialysis population. Clin Nephrol 2000; 54: 455-462. Cervical screening in Australia 1997-1998. Canberra: Australian Institute of Health and Welfare, 2000. (AIHW Cat. No. CAN 9.) BreastScreen Australia achievement report 1997 and 1998. Canberra: Australian Institute of Health and Welfare, 2000. (AIHW Cat. No. CAN 8.) Weisinger JR. Role of hormone replacement in the management of osteoporosis in haemodialysis women: perspectives for the future. Nephrol Dial Transplant 2000; 15 Suppl 5: 36-37. Hampson J, Roberts R, Morgan D. Shared care: a review of the literature. Fam Pract 1996; 13: 264-279. Smith R, de Looze F, Kelly B, Rigby R. "Shared care". An integrated model of service delivery for renal and renal transplant patients [abstract]. Abstracts of the 35th Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology; 3-5 Mar, 1999; Brisbane (QLD). Make a comment

Carmel M Hawley

Abstract Objectives: To describe reproductive health issues in women with end-stage renal disease (ESRD) treated with haemodialysis. Study design: Cross-sectional survey based on structured interviews. Setting: Nephrology units of two major metropolitan tertiary referral hospitals in Victoria and their satellite dialysis centres between 1 November 1998 to 30 June 1999. Methods:Women aged 20 years or over in haemodialysis programs. Outcome measures: Menstrual status; prevalence of menstrual and climacteric symptoms; use of gynaecological screening; and prevalence of comorbidities that may benefit from hormone replacment therapy. Results: 48 women completed the survey. They were similar to the 485 women undergoing haemodialysis in Victoria in age (mean age, 55.5 years; range, 20-84 years), years on dialysis (mean age, 3.9 years; range, 1 month-17 years) and primary diagnosis. Eleven of the 15 premenopausal women reported menstrual cycles of 22-35 days, 13 reported common premenstrual symptoms, and six reported dysmenorrhoea that interfered with daily activities. Average age at menopause was 47.7 years (95% CI, 45.6-49.9 years), and six of the 31 postmenopausal women underwent menopause before 45 years. Eight had ever been prescribed hormone replacement therapy (oral in all cases). Over half the women (26) had not had a Pap smear in the last two years, and 12 of those aged over 50 (38%) had not had a mammogram in the same period. Conclusion:Despite their risk of early menopause, cardiovascular disease and bone fracture, few women undergoing haemodialysis were offered hormone replacement therapy. Nor were they adequately screened for gynaecological cancers. Women's health issues seem to be neglected among haemodialysis patients. Chronic renal failure is associated with neuroendocrine disturbances, menstrual disorders and sexual dysfunction,1 and it has been generally accepted that most women undergoing long-term haemodialysis are amenorrhoeic.2,3 However, a North American study noted that the development of strategies to address women's health issues among haemodialysis patients is limited by lack of information about their menstrual patterns, menopausal symptoms, sexual function and use of preventive screening.4 The situation is similar in Australia. As nephrologists increasingly assume the role of primary healthcare providers for haemodialysis patients, with the role of general practitioners less well defined, routine health matters may be overlooked. The problem is increasing as more people enter dialysis programs for end-stage renal disease (ESRD),5 and as their survival improves. Issues unique to women undergoing haemodialysis deserve greater attention. Our aim was to describe the menstrual status, prevalence of menstrual and climacteric symptoms, comorbidities that may benefit from hormone replacement therapy and use of gynaecological cancer screening among women undergoing haemodialysis for ESRD in Victoria. Methods The study was a cross-sectional survey based on structured interviews. Ethics approval was obtained from the research and ethics committees of both Monash Medical Centre and St Vincent's Hospital, Melbourne. Participants Women were eligible if they were aged 20 years or over and were undergoing haemodialysis for ESRD at two tertiary care hospitals (Monash Medical Centre and St Vincent's Hospital, Melbourne) or their associated satellite dialysis centres in Victoria during the survey period, 1 November 1998 to 30 June 1999. Participants were identified from haemodialysis schedules provided by each centre. Exclusion criteria included inadequate spoken English, acute illness and inability to give written informed consent. Survey procedure Participants were interviewed by a psychologist (V S W) at the centre where they underwent haemodialysis (43 women), or, for those undergoing home haemodialysis, by telephone (4) or at home (1). The survey asked about demographic details, history of renal disease, menstrual history, menstrual or menopausal symptoms, pregnancies, gynaecological surgery, sexual function, use of Pap smears and mammograms, medications and comorbidities (eg, diabetes mellitus, cardiovascular disease and osteoporosis). Data analysis Frequencies were compared using the χ2 test (Yates corrected where appropriate) or Fisher's exact test, if the expected cell frequency was less than 5. Results Between 1 November 1998 and 30 June 1999, 73 women aged 20 years and over were listed as undergoing haemodialysis at participating centres. Forty-eight (66%) completed the survey, and 19 were excluded (non-English-speaking [11], too ill [5] or died, changed to peritoneal dialysis or underwent kidney transplantation before interview [1 each]), four were unavailable, and two declined interview. In Victoria as a whole, 485 women aged 20 years or over had haemodialysis in the study period.4 Participant characteristics The 48 participants were aged 20 to 84 years. Their age distribution and documented cause of ESRD matched closely those of the female haemodialysis population in Victoria5(Box 1). Average duration of dialysis was 3.9 years (range, 1 month to 17 years), also matching the average duration for female haemodialysis patients in Victoria (mean, 3.9 years; range, 1 month to 25 years).5 Twenty-seven women (56%) were married or in a defacto relationship, 12 (25%) were widowed or divorced, and nine (19%) were single. There are no comparable Victorian data for relationship status. Menstrual or menopausal status Fifteen women (31%) were classified as premenopausal (< 12 months amenorrhoea and no climacteric symptoms), including one who was taking medroxyprogesterone acetate and had irregular menses. Thirty-one women (65%) were classified as postmenopausal (> 12 months amenorrhoea, surgical menopause or irregular cycles, and persistent vasomotor symptoms), while two (4%) were classified as perimenopausal as they had climacteric symptoms but had not been amenorrhoeic for 12 months (ages, 46 and 47 years). Twenty-four women (50%) reported previous gynaecological surgery; 11 (23%) had had a hysterectomy. Premenopausal women: Ten of the 15 premenopausal women reported regular menstrual cycles. For 11 women, length of cycles fell between 22 and 35 days. Duration of bleeding was 3-9 days (12 women), less than 3 days (2, including the woman taking medroxyprogesterone acetate) and longer than 9 days (1). Bleeding was described as moderate or heavy by 14 women. Premenstrual symptoms were reported by 13 of the 15 premenopausal women (Box 2). Seven reported dysmenorrhoea, which interfered with daily activities in six, and for which four took medication. Postmenopausal women: 31 women were postmenopausal, for between 1.5 and 44 years. Two women had had surgically induced menopause (hysterectomy and bilateral oophorectomy). Of the 29 with non-surgical menopause, 27 reported their age at the time. Their average age at menopause was 47.7 years (95% CI, 45.6-49.9 years). Six women experienced early menopause (< 45 years), including one woman with premature menopause at 35 years. Three women experienced menopause after begining haemodialysis (at ages 49 [2 women] and 53 years [1]). Oestrogen-deficiency symptoms are shown in Box 2. Twelve postmenopausal women and one perimenopausal woman reported that their doctors had ever suggested hormone replacement therapy (HRT), and eight (all postmenopausal) had been prescribed this therapy — oral HRT in all cases. Pregnancies Thirty-seven of the 48 participants (77%) reported having been pregnant, and all but two of these had given birth to at least one child. We did not explore the relationship between pregnancy and dialysis. Sexual function Twenty-five women reported being in a sexual relationship (20 of the 24 who were married or in a defacto relationship and five of the 23 who were single, divorced or widowed). Among postmenopausal women, those who had been prescribed HRT were more likely to be in a sexual relationship (7 of 8 versus 9 of 22 not prescribed HRT; P = 0.04). Eight premenopausal women reported being in a sexual relationship; three of these were not using contraception and had not had a tubal ligation or hysterectomy (ages, 34, 41 and 51 years). Of 42 women who responded to the question "Are you experiencing diminished sexual interest?", 14 answered that they were (33%). Three of 15 premenopausal women reported diminished sexual interest, compared with 10 of 25 postmenopausal women, a difference which was not statistically significant (P = 0.30). Four women reported that this was problematic in their relationships (one premenopausal, one perimenopausal and two postmenopausal women). Breast and cervical cancer screening Most recent screening for breast or cervical cancer is shown in Box 3. Twenty-two women (45%) reported that they had had a Pap smear within the previous two years. This was more likely among premenopausal than postmenopausal women (11 of 15 versus 10 of 31; P = 0.02). Three of the 15 women on the current renal transplant list had not had a Pap smear within the previous two years and did not report having a hysterectomy (ages, 20, 38 and 57 years). Ten women (21%) reported never having a Pap smear. Breast self-examination was performed regularly by 24 of the 36 women who had been shown how to do this by a medical practitioner, and by none of the 12 women who had never been shown (χ2= 13.44; P < 0.001). Of the 31 women aged 50 years or over, 19 (62%) had had a mammogram within the previous two years. Five women reported a family history of breast cancer, and three of these had had a mammogram within the previous two years, while one (aged 50) had never had a mammogram, and the other (aged 79) had had a mammogram over 10 years before. Medications and comorbidities All women were taking some form of medication. Forty-six of the 48 were taking caltrate or calcitriol, and 37 were taking erythropoietin. Fourteen women were being treated for hyperlipidaemia, and 26 for hypertension. Seven women were current cigarette smokers. Ten women (21%) had diabetes mellitus, and 18 (38%) had cardiovascular disease. Prevalence of cardiovascular disease was greater in those with a family history (14 of 24 versus 4 of 24 with no family history; χ2= 7.20; P = 0.007), but was not increased among those with diabetes (5 of 10 versus 13 of 38 without diabetes; P = 0.47). Fourteen women had a history of bone fracture, 11 of whom were postmenopausal. Only one postmenopausal woman with past fracture was taking HRT at the time of the fracture, and two had previously taken HRT. None had been prescribed a bisphosphonate. Risk of fracture was higher in women with a family history of osteoporosis (6 of 8 versus 8 of 40 with no family history; P = 0.005). Discussion We found that the average age of menopause among women undergoing haemodialysis in our study was 47.7 years. About a third of the women were premenopausal, and most of these had menstrual cycles which appeared ovulatory on the basis of cycle length and regularity and presence of premenstrual symptoms.6A third of women who answered a question about sexual interest reported that it was diminished. More than half the women had not had a Pap smear in the previous two years, and more than a third of those aged over 50 years had not had a mammogram in this period. Although our sample was small, it was representative of the adult female haemodialysis population of Victoria in terms of age, cause of ESRD and time on dialysis. Our finding that most premenopausal women had apparently ovulatory menstrual cycles accords with results of a 1997 study of North American women.3 In contrast, earlier studies suggested a high rate of amenorrhoea among women with ESRD, and this difference has been attributed partly to the introduction of recombinant human erythropoietin to correct the anaemia of chronic renal failure in the late 1980s.1Erythropoietin reduces prolactin levels7 and may thereby restore ovulation and improve sexual function. Correction of anaemia, and consequent improved well-being, appetite and nutritional status, could also contribute to improved reproductive function.8,9 Greater emphasis over the past decade on delivery of adequate dialysis may have similar effects, although definitive evidence is lacking. Women with ESRD tend to undergo menopause earlier than healthy women, at an average age of 4710 versus 51.5 years.11 Mean age in our participants (47.7 years) is consistent with previous findings.10,4 The hysterectomy rate of 23% in our participants reflects the rate reported for Australian women overall.12 Sexual dysfunction is a feature of chronic renal failure, with many women complaining of decreased libido and inability to achieve orgasm.11 In our study, a third of responding women reported diminished sexual interest. This occurred despite the high rate of erythropoietin use. Clearly, the pathogenesis of sexual dysfunction is complex, involving not only hormonal factors, but also psychological concerns, body image, nutritional status and comorbid medical conditions. It appeared that sexual issues and contraception among these women were not being adequately addressed. Another concern is that a large proportion of women in this group had not been screened for gynaecological cancers according to current guidelines. In Australia, all women are advised to have a Pap smear every two years from the age of 18, or commencement of sexual activity, until the age of 70.13 Screening mammography for breast cancer is recommended two-yearly for women between the ages of 50 and 70 years.14 Although these guidelines are not followed by all women in the general population, women undergoing haemodialysis have increased risk of gynaecological malignancies,10 which may indeed increase further with immunosuppression after transplantation. The failure of three women on the transplant waiting list to have recommended cervical screening suggests poor clinical practice. The leading cause of death among postmenopausal women with ESRD is cardiovascular disease (42% of all deaths).5 Nearly 38% of our study population reported having cardiovascular disease, which was significantly associated with family history, but not diabetes. The extent to which the excessive cardiovascular mortality of ESRD is a consequence of oestrogen deficiency exacerbating the adverse lipoprotein lipid profile of the anephric state requires investigation.15 In addition, a third of postmenopausal women reported a history of fracture and are at considerable risk of recurrent fracture.16 The role of HRT in postmenopausal women undergoing dialysis is uncertain. While benefits would be expected in terms of fracture prevention, they must be weighed against possible complications, especially thrombosis. In particular, patients bearing fistulas made from artificial materials (eg, polytetrafluoroethylene) appear to have a higher risk of thrombosis if their haemoglobin concentration is higher than 12g/dL.17The risk may be further exacerbated by routine erythropoietin use. Women on maintenance haemodialysis have impaired oestrogen clearance,15 and hence oestrogen therapy should be low dose. Transdermal therapy is preferable to oral therapy, as it is less likely to be procoagulant,18 and circulating levels can be monitored.15 All women treated with HRT in our study were taking it orally. None used local vaginal oestrogen, which, considering the high frequency of sexual problems, is surprising. Dialysis patients have complex health problems requiring specialist care which, combined with their frequent hospital attendance, can result in neglect of the routine health management normally undertaken in general practice. Our findings highlight the need for comprehensive well-woman care programs in dialysis units, incorporating cancer screening, sexual counselling, contraceptive advice, menopausal management and fracture prevention. References Lim VS, Henriquez C, Sievertsen G, Frohman LA. Erythropoietin causes hormonal changes in haemodialysis patients? Ann Intern Med 1980; 93: 21-27. Perez RJ, Lipner H, Abdulla N, et al. Menstrual dysfunction of patients undergoing chronic haemodialysis. Obstet Gynecol 1978; 51: 552-555. Lim VS, Henriquez C, Sievertsen G, Frohman LA. Ovarian function in chronic renal failure: evidence suggesting hypothalamic anovulation. Ann Intern Med 1980; 93: 21-27. Holley JL, Schmidt RJ, Bender FH, et al. Gynaecologic and reproductive issues in women on dialysis. Am J Kidney Dis 1997; 29: 685-690. Disney APS, Russ GR, Walker R, et al. ANZ DATA Registry Report 1998. Adelaide: Australian and New Zealand Dialysis and Transplant Registry, 1999. Mortola JF. Premenstrual syndrome. Curr Ther Endocrinol Metab 1997; 6: 251-256. Schaefer RM, Kotot F, Wernze H, et al. Improved sexual function in haemodialysis patients on recombinant erythropoietin: A possible role for prolactin. Clin Nephrol 1989; 31: 1-5. Tarng DC, Huang TP, Doong TI. Improvement of nutritional status in patients receiving maintenance haemodialyis after correction of renal anemia with recombinant human erythropoietin. Nephron 1998; 78: 253-259. Steffenson G, Aunsholt NA. Does erythropoietin cause hormonal changes in haemodialysis patients? Nephrol Dial Transplant 1993; 8: 1215-1218. Gipson D, Katz LA, Stehman-Breen C. Principles of dialysis: special issues in women. Semin Nephrol 1999; 19: 140-147. Palmer B. Sexual dysfunction in uremia. J Am Soc Nephrol 1999; 10: 1381-1388. Dennerstein L, Shelley J, Smith AM, Ryan M. Hysterectomy experience among mid-aged Australian women. Med J Aust 1994; 161: 311-313. National Health and Medical Research Council. Cervical cancer screening: interval of screening. Canberra: Commonwealth of Australia, 1991. Baker P, Raineri T, Nichols A. Increasing breast and cervical screening rates. Curr Ther 1999; 40 (12): 30-33. Ginsburg ES, Owen W, Greenberg L, et al. Estrogen absorption and metabolism in women with endstage renal failure. J Clin Endocrinol Metab 1996; 81: 4414-4417. Cummings SR, Nevitt M, Browner WS, et al. Risk factors for hip fracture in white women. N Engl J Med 1995; 332: 767-773. Watschinger B, Watzinger U, Templ H, et al. Effect of recombinant erythropoietin on anterior pituitary homones on chronic haemodialysis. Horm Res 1991; 36: 26. Scarabin P-Y, Allhene-Gelas M, Plu-Bureau G, et al. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. Arterioscler Thromb Vasc Biol 1997; 17: 3071-3078. (Received 27 Nov 2000, accepted 14 May 2001) Authors' details Jean Hailes Foundation Research Unit, Melbourne, VIC. Christina Jang, MB BS, Research Registrar; Robin J Bell, PhD, FAFPHM, Consultant Epidemiologist; Vikki S White, Grad Dip Appl Psych, MPH, Research Coordinator; Susan R Davis, PhD, FRACP, Director of Research, and Associate Professor, Department of Preventive Medicine, Monash University, Melbourne, VIC. St Vincent's Hospital, Melbourne, VIC. Petrova S Lee, FRACP, Nephrologist; Karen M Dwyer, MB BS, Nephrology Registrar. Monash Medical Centre, Melbourne, VIC. Peter G Kerr, PhD, FRACP, Deputy Director of Nephrology. Reprints will not be available from the authors. Correspondence: Dr S R Davis, The Jean Hailes Foundation Research Unit, 173 Carinish Road, Clayton, VIC 3168. suedavisATnetlink.com.au Make a comment

Christina Jang · Robin J Bell · Vikki S White · Petrova S Lee · Karen M Dwyer · Peter G Kerr · Susan R Davis

Indigenous health Regional variation in the incidence of end-stage renal disease in Indigenous Australians Alan Cass, Joan Cunningham, Zhiqiang Wang and Wendy Hoy MJA 2001; 175: 24-27 Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Aboriginal health Abstract Objective: To evaluate regional variation in the incidence of end-stage renal disease (ESRD) in Indigenous Australians, and to examine the proximity to ESRD treatment facilities of Indigenous patients. Design: Secondary data review, with collection of primary data regarding patients' place of residence before beginning ESRD treatment. Participants: Indigenous ESRD patients who commenced treatment in Australia during 1993-1998. Methods: We obtained data from the Australian and New Zealand Dialysis and Transplant Registry regarding 719 Indigenous patients who started ESRD treatment between 1 January 1993 and 31 December 1998. We obtained primary data from the treating renal units to determine the place of residence before beginning renal replacement therapy. We calculated the average annual incidence of ESRD for each of the 36 Aboriginal and Torres Strait Islander Commission regions using population estimates based on the 1996 Census, and calculated standardised incidence ratios with 95% confidence intervals for each region. We compared the number of cases with the treatment facilities available in each region. Main outcome measure: Regional standardised ESRD incidence for Indigenous Australians referenced to the total resident population of Australia. Results: Standardised ESRD incidence among Indigenous Australians is highest in remote regions, where it is up to 30 times the national incidence for all Australians. In urban regions the standardised incidence is much lower, but remains significantly higher than the national incidence. Forty-eight per cent of Indigenous ESRD patients come from regions without dialysis or transplant facilities and 16.3% from regions with only satellite dialysis facilities. Conclusions: There is marked regional variation in the incidence of ESRD among Indigenous Australians. Because of the location of treatment centres, there is inequitable access to ESRD treatment services for a significant proportion of Indigenous patients. In Australia, geographical differences in morbidity and mortality have been demonstrated.1-4 In general, people living in rural and remote areas have higher death and hospital separation rates, which have been attributed to differences in socioeconomic status,1,3-5 access to health services,2,6,7 ethnicity4 and racial discrimination.8 Indigenous Australians constitute a disproportionate number of new patients commencing end-stage renal disease (ESRD) treatment:9 in 1997, the incidence rate (adjusted for age and sex) for Indigenous Australians beginning ESRD treatment was nearly nine times that of non-Indigenous Australians.10 Although epidemics of renal disease among Indigenous Australians in defined areas11 have been documented, there have been no systematic reports of the regional patterns of ESRD incidence in Australia. In this study we have attempted to determine these patterns and to examine the accessibility of ESRD treatment facilities for Indigenous people. Methods Databases The Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) maintains a database of patients treated by maintenance dialysis or renal transplantation in Australia. All renal units that provide ESRD treatment in Australia participate in the Registry. Postcode of residence at the start of treatment is collected for all new patients entered into the ANZDATA Registry. ANZDATA maintains a list of hospital renal transplant services, tertiary referral units and satellite dialysis units. Satellite units are defined as dialysis facilities, generally staffed by specialist nurses, that are geographically separate from hospital nephrology services. Data validity Postcode of residence at the start of treatment is an imperfect indicator of the usual place of residence before starting treatment. In remote areas of Australia a single postcode may apply to many communities across a vast area. Furthermore, patients may be required to relocate to a major regional centre to access dialysis services; thus, their postcode at the start of treatment may not reflect their previous usual place of residence. To determine the usefulness of postcode data, we reviewed 104 Indigenous patients who commenced ESRD treatment from 1993 to 1998 at Royal Darwin Hospital, Northern Territory. For these patients the previous usual place of residence was known. Fifty-one patients (49%) had postcodes in the Darwin region, but only nine of these 51 patients previously lived in this region. The other 42 had relocated to Darwin to commence dialysis and were from communities across the "Top End", extending from the Torres Strait in Queensland to Geraldton in Western Australia. As a result of this audit, we decided to collect primary data from each treating renal unit regarding the previous place of usual residence of their Indigenous patients. Indigenous identification was based upon self-identification and discussion with the treating physician. There is often significant concern about the quality of Indigenous identification in morbidity, mortality and demographic data sets. However, we believe that racial identification in the ANZDATA registry is good. A survey form is completed every six months for all patients on maintenance dialysis or with functioning renal transplants. In this survey, question five is about "Racial origin" and includes a prompt regarding Indigenous status. ESRD patients have regular contact with renal services from the time of diagnosis, through intensive maintenance therapy until death. There is heightened awareness of renal disease in Indigenous Australians and multiple opportunities exist to reconfirm data accuracy. Patients From 1 January 1993 to 31 December 1998, 719 Indigenous patients started treatment for ESRD in Australia. We determined the previous place of usual residence for 680 (94.6%). For 38 patients (5.3%) we used the postcode at entry as an indicator of previous place of usual residence. No geographical data were obtainable for one patient. Geography We used the 36 Aboriginal and Torres Strait Islander Commission (ATSIC) regions (Boxes 1 and 2) as our geographic units for analysis. These are legally prescribed administrative areas and the smallest geographical areas for which accurate resident population estimates for the Indigenous population are available.12 We assigned the place of usual residence for Indigenous patients to the appropriate ATSIC regions. We assigned the 38 patients for whom we could not obtain exact information on previous place of residence to ATSIC regions according to their postcode at the time of beginning ESRD treatment. Statistical analysis Using population estimates based on the 1996 Census, we calculated the average annual incidence of ESRD in the 36 ATSIC regions. We used ABS estimates of the Indigenous population, derived using Census information on place of usual residence. These estimates are adjusted for net Census undercount and non-response to the Census question about Indigenous status.13 We used indirect standardisation to calculate an age- and sex-standardised incidence ratio with 95% confidence intervals for each region. Rates for the total Australian resident population were used as the reference (standardised incidence ratio equals incidence in the Indigenous population divided by incidence in the total Australian population, after adjusting for differences in the age and sex composition of both populations). Statistical analysis was performed using Stata.14 Ethical approval We obtained ANZDATA approval to analyse geographic data for Indigenous patients starting treatment for ESRD between 1 January 1993 and 31 December 1998. We also obtained approval for the study from the joint institutional ethics committee of Royal Darwin Hospital and the Menzies School of Health Research. The head of each renal unit gave written consent for us to access potentially identifying patient data in order to determine the previous place of usual residence for Indigenous ESRD patients. Results Mapping reveals significant variation in the incidence of ESRD among Indigenous Australians. The areas of highest incidence (up to 1300 cases per million per year) were the remote regions of Tennant Creek, Aputula and Jabiru in the Northern Territory, Warburton and Kalgoorlie in Western Australia, and Ceduna in South Australia (Box 1). The areas of lowest incidence (less than 100 per million per year) were the regions of Rockhampton and Brisbane in Queensland, Sydney and Queanbeyan in NSW/ACT, Wangaratta (which includes much of eastern Victoria) and Hobart (which encompasses all of Tasmania) (Box 1). The standardised incidence ratio for ESRD (compared with the total national population incidence) ranged from less than two in Rockhampton, Sydney, Queanbeyan and Wangaratta to more than 25 in Aputula, Kalgoorlie and Tennant Creek (Box 2). There were no ESRD patients identified as Indigenous in Tasmania in the six-year period. Tertiary renal services, particularly transplant services, are located within significant population centres such as capital cities. Three hundred and forty-five (48.0%) of the 719 Indigenous ESRD patients lived in ATSIC regions without ESRD treatment facilities (Box 2). A further 117 (16.3%) lived in regions with only satellite dialysis facilities (Box 2). Most Indigenous patients must travel hundreds of kilometres to access transplant services, which are located in Perth, Adelaide, Melbourne, Sydney, Newcastle and Brisbane. Discussion In this study we have demonstrated a large gradient in Indigenous ESRD incidence from urban to remote regions and highlighted inequitable access for remote patients to treatment facilities. However, even in urban regions, the Indigenous ESRD incidence was high after age and sex standardisation. Poor Indigenous health outcomes are not confined to the most disadvantaged or most remote regions, but exist across the Indigenous population. The quality of Indigenous identification is a potential concern in our study. ANZDATA relies upon self-identification and discussion with the treating physician. Self-identification is the method used by the Australian Bureau of Statistics in census collections and is generally used in health-related data collection. We believe that the quality of identification in our study is high owing to the ongoing intensive interaction of ESRD patients with medical and nursing staff, Indigenous status being a prominent question in the six-monthly survey form, and the strong awareness of Indigenous ESRD among nephrologists. The most likely error would be the failure to identify all urban Indigenous ESRD patients. This would result in an underestimate of the true Indigenous ESRD incidence in urban areas and an overestimate of the gradient from urban to remote Indigenous ESRD incidence. Yet, as this gradient is so large, representing an almost 20-fold variation in standardised ESRD incidence, it can not be entirely explained by problems with Indigenous identification. The very high standardised incidence ratios for Indigenous people in remote areas would not change. These results have significant implications for the delivery of services to Indigenous people with ESRD. Satellite facilities opened in the Jabiru region in 1999 and the Katherine region in 2000 (after the patients in this study commenced treatment). Of the 16 regions with the highest Indigenous ESRD incidence, at the beginning of 2001 only Kalgoorlie, Jabiru (Tiwi Islands), Geraldton, Katherine and South Hedland had satellite dialysis units. A satellite unit is scheduled to open soon in Broome and recommendations have been accepted to establish a satellite haemodialysis service in the Torres Strait as part of the recent Queensland Renal Strategy.15 We recognise the significant difficulties related to the establishment and maintenance of renal treatment facilities in remote locations. These include high construction costs, poor reliability of electricity and water supply, variable water quality, difficulties in training and retaining specialised nursing staff, infrequent access to medical staff and provision of housing for patients returning to live in their local community. Despite these difficulties, treatment facilities have been established in some of the most remote communities in Australia. Even with the availability of satellite units, initiation of ESRD treatment usually requires a prolonged stay in a major urban centre. During this stay, vascular or peritoneal access for dialysis is created, the patient starts and is stabilised on treatment and learns skills required for self-care in order to return to a remote satellite dialysis unit. We should develop more innovative methods of patient education, training for self-care and delivery of treatment to allow patients to remain within their communities whenever possible. Improving prevention and treatment services in high-incidence areas should be a priority. Indigenous people living in remote communities demand more equitable access to dialysis services,16 regardless of practical problems related to the establishment of remote treatment facilities. The need to relocate to distant urban areas to access treatment affects the patient, patient's family and community. A recent study of ESRD among Aboriginal people of central Australia concluded: "This level of illness and death [due to ESRD] represents Aboriginal family trauma and loss on a shocking scale, described without exaggeration as sorrows nearly every year [because] the young and the old are dying". 17 Acknowledgements The data reported here have been supplied by the Australia and New Zealand Dialysis and Transplant Registry. The interpretation of these data is the responsibility of the authors and should not be seen as an official policy or interpretation of the Australia and New Zealand Dialysis and Transplant Registry. Dr Alan Cass receives postgraduate research scholarship funding from the Colonial Foundation. Dr Joan Cunningham is supported by a fellowship from the Menzies Foundation. We thank Dr Mark Thomas, Dr Paul Snelling, Dr Meshak Kirubakaran, Dr Tim Furlong, Dr Peter de Jersey and the heads of renal units for providing information regarding the place of usual residence for their patients. References Glover J, Harris K, Tennant S. A social health atlas of Australia. 2nd ed. Adelaide: Public Health Information Development Unit, University of Adelaide, 1999. Sexton PT, Sexton TL. Excess coronary mortality among Australian men and women living outside the capital city statistical divisions. Med J Aust 2000; 172: 370-374 [see comments Med J Aust 2000; 172: 360-361]. National Health Strategy. Enough to make you sick: how income and environment affect health, Research Paper No. 1. Melbourne: National Health Strategy Unit, 1992. Taylor R, Chey T, Bauman A, Webster I. Socio-economic, migrant and geographic differentials in coronary heart disease occurrence in New South Wales. Aust N Z J Public Health 1999; 23: 20-26. Turrell G, Mathers CD. Socioeconomic status and health in Australia. Med J Aust 2000; 172: 434-438. Heller RF. Mortality from cardiovascular disease is too high outside capital cities [editorial]. Med J Aust 2000; 172: 360-361. McLaren B. Renal failure in Arnhem Land: missed opportunities for prevention and treatment. Aust J Rural Health 1996; 4: 61-66. Lowe M, Kerridge IH, Mitchell KR. 'These sorts of people don't do very well': race and allocation of health care resources. J Med Ethics 1995; 21: 356-360. Disney A, Russ G, Walker R, et al, editors. ANZDATA Registry Report 1999. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1999. Cass A, McDonald SP, Wang Z. Australians with renal disease: a new national survey [letter]. Med J Aust 1999; 171: 444. Spencer JL, Silva DT, Snelling P, Hoy WE. An epidemic of renal failure among Australian Aboriginals. Med J Aust 1998; 168: 537-541 [see comments Med J Aust 1998; 168: 532-533 and Med J Aust 1999; 170: 191-192]. Australian Bureau of Statistics. Population issues, Indigenous Australians. Canberra: Australian Bureau of Statistics, 1999. Australian Bureau of Statistics. Experimental estimates of the Aboriginal and Torres Strait Islander population. Canberra: Australian Bureau of Statistics, 1998. Stata version 6 [computer software]. College Station, TX: Stata Corporation, 1999. Schmidt B. Northern zone renal services plan 2000-2010, 2000. Devitt J, McMasters A. On the machine: Aboriginal stories about kidney troubles. Alice Springs: IAD Press, 1998. Devitt J, McMasters A. Living on medicine: a cultural study of end-stage renal disease among Aboriginal people. Alice Springs: IAD Press, 1998. (Received 13 Sep 2000, accepted 22 Mar 2001) Authors' details Menzies School of Health Research, Casuarina, NT. Alan Cass, GradDipClinEpi, FRACP, PhD Student and Nephrologist. Joan Cunningham, ScD, Epidemiologist and Menzies Fellow. Zhiqiang Wang, PhD, Biostatistician. Wendy Hoy, MB BS, FRACP, Head of Renal Unit. No reprints will be available from the authors. Correspondence: Dr Alan Cass, Menzies School of Health Research, PO Box 41096, Casuarina, NT, 0811. Make a comment Map numbers refer to Aboriginal and Torres Strait Islander Commission regions as specified in Box 2 Back to text 2: End-stage renal disease among Indigenous Australians from 1993 to 1998 ATSIC region (map references) Treatment facilities† Patients (number) Standardised incidence ratio* (95% CI) Tennant Creek (35) 30 31.05 (20.96 - 44.33) Kalgoorlie (27) S 23 27.75 (17.60 - 41.64) Aputula (33) 58 25.03 (19.01 - 32.36) Warburton (23) 20 22.77 (13.91 - 35.17) Ceduna (18) 10 22.48 (10.78 - 41.34) Jabiru (31) 45 21.87 (15.95 - 29.26) Geraldton (28) S 25 18.20 (11.78 - 26.86) Mount Isa (11) 33 17.74 (12.21 - 24.91) Kununurra (22) 22 16.85 (10.56 - 25.51) Katherine (32) 30 15.64 (10.56 - 22.33) Torres Strait (15) 28 14.99 (9.96 - 21.66) South Hedland (25) S 18 14.75 (8.74 - 23.30) Derby (26) 16 13.40 (7.66 - 21.76) Nhulunbuy (34) 21 11.74 (7.27 - 17.94) Cooktown (12) 21 11.61 (7.19 - 17.75) Broome (21) 11 11.47 (5.73 - 20.53) Port Augusta (19) S 17 10.45 (6.09 - 16.74) Bourke (2) S 21 10.16 (6.29 - 15.53) Townsville (16) T, S 35 9.41 (6.55 - 13.08) Cairns (10) T, S 35 8.71 (6.07 - 12.12) Alice Springs (30) T, S 11 8.55 (4.27 - 15.30) Narrogin (24) S 13 8.20 (4.37 - 14.02) Darwin (36) T, S 17 7.02 (4.09 - 11.24) Perth (20) Tx, T, S 29 6.70 (4.48 - 9.61) Adelaide (17) Tx, T, S 15 4.62 (2.58 - 7.61) Tamworth (5) T, S 12 4.18 (2.16 - 7.30) Roma (14) T, S 8 3.70 (1.60 - 7.28) Coffs Harbour (3) Tx, T, S 24 3.68 (2.36 - 5.47) Ballarat (8) Tx, T, S 10 3.42 (1.64 - 6.28) Wagga Wagga (6) T, S 14 2.98 (1.63 - 5.00) Brisbane (9) Tx, T, S 17 2.51 (1.46 - 4.02) Rockhampton (13) T, S 5 1.78 (0.58 - 4.16) Sydney (4) Tx, T, S 16 1.77 (1.01 - 2.88) Queanbeyan (1) T, S 4 1.75 (0.48 - 4.48) Wangaratta (7) Tx, T, S 4 1.39 (0.38 - 3.55) Hobart (29) T, S 0 0.00 (0.00 - 1.03) * Indirectly standardised to the rates for the total Australian resident population. †Tx = transplant service, T = tertiary renal unit, S = satellite dialysis unit. Geographical data were unobtainable for one patient. Back to text

Alan Cass · Joan Cunningham · Zhiqiang Wang · Wendy Hoy

Editorial How bright is their future? Post-streptococcal glomerulonephritis in Indigenous communities in Australia Streptococcal skin infection may have a major role in the epidemic of chronic renal disease among Indigenous Australians. MJA 2001; 174: 489-490 In 1836, Richard Bright, from Guy's Hospital, London, described the clinical entity of acute glomerulonephritis, later known as Bright's disease. However, it was not until 1907 that streptococci were suggested as a cause of acute glomerulonephritis. At that time, post-streptococcal glomerulonephritis (PSGN) was rife throughout the world, as it remains today in some developing countries. With increasing living standards, Australia has a very low overall incidence of streptococcal infection, but, in contrast, our Indigenous communities have one of the highest incidences in the world, and corresponding high incidences of PSGN and rheumatic heart disease.1-4In this issue of the Journal, White and colleagues highlight anew the problem of the health of our Indigenous communities and provide some ominous insight into the long-term sequelae of PSGN.5 It has been contentious whether PSGN is a relatively benign disease, as traditionally thought, or whether, as suggested 25 years ago, it may lead to progressive renal disease and eventually end-stage renal failure.6 The reported study of albuminuria and haematuria — the harbingers of progressive renal disease — in a remote Aboriginal community suggests that the latter is correct. The study found that people with a history of PSGN in childhood had a risk of overt albuminuria more than six times that in the control group. In fact, the data show that a quarter of cases of overt albuminuria in this population may be attributable to PSGN in childhood. This is alarming, particularly as the Aboriginal population has an incidence of end-stage renal failure 10 times greater than that of the non-Aboriginal population of Australia.1,7,8 It is even more distressing when we realise that streptococcal disease should theoretically be preventable. Proteinuria is increasingly recognised as the best overall indicator of progressive renal disease, whatever the cause. It would thus be very important to follow the study population, preferably over many more years, to determine whether renal damage does indeed progress and lead to end-stage renal failure. Other aspects of epidemic and endemic post-streptococcal infection could also be explored. It has been suggested that, because of the high rate of nephritis in families, a familial trait may be involved, increasing susceptibility to the disease.9 This may have some relevance to the PSGN epidemics in this population. There is no simple treatment for PSGN, and preventing streptococcal infection remains the most important control strategy.10 Penicillin is beneficial in preventing spread of infection during epidemics.2 No vaccine is as yet available. As concluded by White and colleagues, prevention of streptococcal infection through improved economic and living conditions, and particularly control of skin infections, is possible and should reduce the incidence of renal involvement. However, the real tragedy highlighted by this study is that, despite the passage of up to 20 years since these children were infected with streptococci, nothing much has changed to lower the rates of infection among Aboriginal children. Indeed, a very recent report demonstrated that skin infections still occur in up to 70% of Aboriginal children, with the major pathogens being group A streptococci.4 It is imperative that such important results are heeded. Not until fundamental changes take place in the social, economic and living conditions of our Indigenous communities will this streptococcal disease be eliminated, as it has been in all other areas of Australia. We have a bipartisan Federal Government committed to improving the health of Indigenous Australians and an office for Aboriginal and Torres Strait Islander Health in the Commonwealth Department of Health and Aged Care, which is providing a comprehensive funding strategy for Indigenous health issues. The head of the Northern Territory Peak Aboriginal Health Organisation, Pat Andersen, is on record as describing the Primary Health Care Access Programme, now under way, as the most exciting event in Aboriginal affairs since the 1967 referendum. Furthermore, recent studies have shown that Aboriginal people can participate enthusiastically and effectively in chronic disease management, with improvement in their renal disease.11 Thus, the challenge at this time of reconciliation is to restore social equity and health to Indigenous Australians.12 It is to be hoped that this will eliminate post-streptococcal disease in Aboriginal communities. The future should be bright. Robert C Atkins Professor of Medicine and Director of Nephrology Monash Medical Centre, Melbourne, VIC Gogna NK, Nossor V, Walker AC. Epidemic of acute poststreptococcal glomerulonephritis in Aboriginal communities. Med J Aust 1983; 1: 64-66. Streeton CL, Hanna JN, Messer RD, Merianos A. An epidemic of acute post-streptococcal glomerulonephritis among aboriginal children. J Paediatr Child Health 1995; 31: 245-248. Carapetis JR, Currie BJ. Preventing rheumatic heart disease in Australia. Med J Aust 1998; 168: 428-429. Currie BJ, Carapetis JR. Skin infections and infestations in Aboriginal communities in northern Australia. Australas J Dermatol 2000; 41: 139-143. White AV, Hoy WE, McCredie DA. Childhood poststreptococcal glomerulonephritis as a risk factor for chronic renal disease in later life. Med J Aust 2001; 174: 492-496. Baldwin DS. Poststreptococcal glomerulonephritis. A progressive disease? Am J Med 1977; 62: 1-11. Briganti E, McNeil J, Atkins RC, editors. The epidemiology of diseases of the kidney and urinary tract: an Australian perspective. Adelaide: Australian Kidney Foundation Report, 1999. Available at <www.med.monash.edu.au/Epidemiology/general_info/publications.html> Spencer JL, Silva DT, Snelling P, Hoy WE. An epidemic of renal failure among Australian Aboriginals. Med J Aust 1998; 168: 537-541. Rodriguez-Iturbe B. Epidemic poststreptococcal glomerulonephritis. Kidney Int 1984; 25: 129-136. Chadban SJ, Atkins RC. Post-infectious glomerulonephritis. In: Brady HR, Wilcox CS. Therapy in nephrology and hypertension. Philadelphia: WB Saunders, 1998: 115-124. Hoy WE, Baker PR, Kelly AM, Wang Z. Reducing premature death and renal failure in Australian Aboriginals. A community-based cardiovascular and renal protective program. Med J Aust 2000; 172: 473-478. Eades SJ. Reconciliation, social equity and Indigenous health [editorial]. Med J Aust 2000; 172: 468-469. Make a comment

Robert C Atkins

Indigenous Health Research Childhood post-streptococcal glomerulonephritis as a risk factor for chronic renal disease in later life Andrew V White, Wendy E Hoy and David A McCredie MJA 2001; 174: 492-496 For editorial comment, see Atkins Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Aboriginal health Abstract Objective: To test the hypothesis that post-streptococcal glomerulonephritis (PSGN) in childhood is a risk factor for chronic renal disease in later life. Design: Retrospective cohort study. Setting: A remote Aboriginal community in the "Top End" of the Northern Territory that experienced two epidemics of PSGN in 1980 and 1987, respectively. Participants: 472 people who were aged 2-15 years during either epidemic. They were categorised by clinical features recorded during the epidemics as having clinically defined PSGN (63), "abnormal urine" (haematuria or proteinuria; 86) or controls (323). Outcome measures: Urinary albumin to creatinine ratio (ACR), haematuria (by dipstick urinalysis), blood pressure, serum creatinine level, and calculated glomerular filtration rate (GFR) during community screening in 1992-1998. Results: Overt albuminuria (ACR > 34 mg/mmol) was present at follow-up in 13% of the PSGN group, 8% of the abnormal urine group, and 4% of the control group. The odds ratio (OR) for overt albuminuria in those with a history of PSGN compared with the control group, adjusted for age and sex, was 6.1 (95% CI, 2.2-16.9). Haematuria (> trace) was present in 21% of the PSGN group compared with 7% of the control group (adjusted OR, 3.7; 95% CI, 1.8-8.0). There were no significant differences between the groups in blood pressure, serum creatinine level or calculated GFR. Conclusion: In this population, a history of PSGN in childhood is a risk factor for albuminuria and haematuria in later life. Although unusual in the rest of Australia, post-streptococcal glomerulonephritis (PSGN) is still common in Aboriginal children living in remote communities, where group A streptococcal pyoderma is endemic.1 In these communities, chronic renal disease and end-stage renal failure also occur in adults at alarming rates.2-4PSGN is usually followed by clinical recovery over several days to weeks, and the long-term outlook has generally been regarded as excellent, with no increase in risk of urinary abnormalities or hypertension.5-7 However, some studies have suggested an increase in rates of chronic renal impairment after this illness.8,9 We aimed to test whether a history of PSGN in childhood is a risk factor for later renal dysfunction in Aboriginal Australians living in a remote community. The main outcome measure used, albumin to creatinine ratio, is a sensitive early marker of renal damage. It has been shown to provide a reliable estimate of 24-hour protein excretion and to predict the rate of decline of glomerular filtration rate and progression to end-stage renal failure in diabetic10 and non-diabetic11 nephropathy. Albuminuria has also been shown to mark early chronic renal disease in this population of Aboriginal Australians, and its progression predicts renal failure, as well as cardiovascular disease and mortality.12,13 Methods Study design This was a retrospective cohort study of children from an isolated Aboriginal coastal community in the "Top End" of the Northern Territory of Australia. The community experienced two epidemics of PSGN in 1980 and 1987, respectively, each lasting for three months.14,15 Children were followed up after these epidemics for a mean of 14.6 years (range, 6-18 years). The study was approved by the Joint Institutional Ethics Committee of the Royal Darwin Hospital and the Menzies School of Health Research, as well as a local community health board. Consent was obtained from each individual or guardian at the time of screening. Participants Participants were 472 people who lived in the community and were aged 2-15 years at the time of either epidemic and who participated in health screening examinations between 1992 and 1998. These 472 people represented 98% of the population of the community in the relevant age groups, according to 1996 census estimates.16 Baseline data During the epidemics, children in the community were screened systematically for oedema, hypertension, and urinary abnormalities on dipstick testing; results were recorded in individuals' medical records in the community. We used these data to categorise children by history during the epidemics: The PSGN group had documented oedema (facial swelling or dependent oedema) or hypertension (diastolic pressure ≥ 80 mmHg if aged 2-12 years and ≥ 85 mmHg if over 12, levels corresponding to the 90th percentile for each age range)17 plus haematuria greater than trace or proteinuria greater than trace on dipstick urinalysis. The "abnormal urine" group had haematuria greater than trace or proteinuria greater than trace, but no oedema or hypertension. The control group comprised children who had normal results on clinical examination and urinalysis (trace or less for blood and protein); children with no symptoms suggesting PSGN, but for whom urinalysis was either not performed or not recorded; and children with no entry in the medical record at the time of the epidemics. Children whose ages were in the range 2-15 years during both epidemics were categorised according to their most abnormal findings in either epidemic. Outcome measures Population health screening was undertaken in the community between 1992 and 1999.14 For people screened more than once, results from the latest screening were used. The albumin to creatinine ratio (ACR) was determined in a random urine sample and was categorised as normal (< 1.1 mg/mmol), suspicious (1.1-3.3 mg/mmol), microalbuminuria (3.4-33 mg/mmol), or overt albuminuria (≥ 34 mg/mmol). Glomerular filtration rate (GFR) was calculated using the formula of Cockroft and Gault.18 Dipstick urinalysis was also performed (Multistix 10SG, Bayer Diagnostics), and blood pressure and serum creatinine level were measured. Analysis Baseline characteristics of the groups were compared using Fisher's exact test for categorical variables and, as not all data followed a normal distribution, the non-parametric Kruskal-Wallis test for continuous variables. Logistic regression estimates were used to obtain adjusted proportions of the population with albuminuria. Odds ratios for the outcomes albuminuria and haematuria were obtained from logistic regression models that included the factors age, sex, birth weight and body mass index. Analyses were performed using Stata statistical software.19Results Baseline characteristics Of the 472 people included in the study, 259 were aged 2-15 years during the 1980 epidemic, and 331 during the 1987 epidemic (with 118 in the age group during both epidemics). Overall, 275 (58%) were male. Categorisation of participants Categorisation of participants according to history during the epidemics is shown in Box 1. Of the 63 children with clinically defined PSGN, all had haematuria and proteinuria, 61 (97%) had oedema and 28 (44%) had hypertension. Although evidence of preceding group A streptococcal infection was not required for classification in the PSGN group, serum antideoxyribonuclease B antibody titres were positive (≥ 1:480) in all 36 of the group in whom they were measured, and serum complement levels were consistent with PSGN (low C3 level) in 35 of the 39 in whom they were measured. Of the 86 participants in the abnormal urine group, 84 (98%) had haematuria, and 24 (28%) had proteinuria. Characteristics of participants at follow-up differed significantly between the groups, with the PSGN group being younger, and the abnormal urine group having a lower proportion of males (Box 2). The three control subgroups also differed at follow-up in median age (normal results subgroup, 26.9 years; no urinalysis subgroup, 17.5 years; and not recorded subgroup, 18.4 years; P = 0.001) and body mass index (normal results subgroup, 20.9 kg/m2; no urinalysis subgroup, 19.1 kg/m2; and not recorded subgroup, 19.8 kg/m2; P = 0.007). However, after adjustment for age and sex, there were no significant differences in height or weight. The control subgroups were combined for analysis. Outcomes On follow-up screening, 104 participants (22%) had albuminuria of any degree (micro- or overt; ACR ≥ 3.4 mg/mmol), 27 (6%) had overt albuminuria (ACR ≥ 34 mg/mmol), and 45 (10%) had haematuria (≥ trace), while 64 (14%) had haematuria or overt albuminuria. Albuminuria and haematuria were more prevalent in the groups with a history of clinical PSGN or abnormal urine during the PSGN epidemics than in the control group (Box 3). In the abnormal urine group, outcomes at follow-up were similar whether or not haematuria had occurred alone or in the presence of proteinuria during the epidemics. As the presence of albuminuria is significantly related to age in this community,14 and as albuminuria was more common in females than males (overt albuminuria occurred in 4% of males and 8% of females; P = 0.044), probabilities were adjusted for age and sex (Box 4). The adjusted probability of overt albuminuria at follow-up was 13.6% after PSGN (95% CI, 6.7%-25%), compared with 2.5% in controls (95% CI, 1.1%-4.8%). Odds ratios for albuminuria and haematuria at follow-up according to history during the epidemics are shown in Box 3. After adjustment for age and sex, the odds of overt albuminuria were more than six times greater after PSGN compared with the control group, while the odds of albuminuria of any degree were more than three times greater. The population-attributable fraction, or proportion of overt albuminuria in the study population that can be attributed to PSGN in childhood, was 24% (95% CI, 5%-40%). After adjustment for age and sex, the odds of haematuria were more than three times greater after PSGN compared with the control group, while the odds of either haematuria or overt albuminuria were five times greater. Only three individuals had both haematuria and overt albuminuria, two of whom had a history of PSGN. Birth weight was available for 429 participants (61 with PSGN, 77 with abnormal urine and 291 controls). Adding birth weight to the logistic regression model gave an odds ratio of 7.6 for overt albuminuria in the PSGN group using controls as the reference (95% CI, 2.5-22.5). Adding body mass index to the model did not significantly alter the odds ratios. There were no significant differences in blood pressure, serum creatinine level or calculated glomerular filtration rate between the groups. Discussion This study indicates that a history of PSGN in childhood is a risk factor for albuminuria and haematuria years later, and suggests that about a quarter of cases of overt albuminuria may be attributable to PSGN in childhood. The incidence of renal disease is high in this population of Aboriginal Australians,12 and other risk factors for renal disease are also common, including low birth weight, recurrent infectious diseases, diabetes and features of syndrome X.3,12,20,21 Possibly, it is the combination of insults that leads to high risk for later renal disease. A prospective cohort study would provide the best evidence. Results of other studies on the contribution of PSGN to chronic renal disease have varied, with some studies reporting no link. For example, two large follow-up studies after epidemic PSGN in Trinidad6,22,23 and Venezuela,7,24 respectively, reported low rates of long-term abnormalities, although the Venezuelan study found that 11.2% of participants had proteinuria of > 500 mg/24 h at 11-year follow-up. These studies had high losses to follow-up (31% and 82%, respectively), and neither had a control group nor assessed microalbuminuria. A cohort study after a PSGN epidemic in an American Indian community found no difference at 10-year follow-up between those who had had PSGN and those who had not in blood pressure, serum creatinine level, proteinuria or haematuria. However, urinary abnormalities were common, being present in 17% of the PSGN group and 13% of the control group.5 In contrast, other studies have reported, similarly to ours, clinically important abnormalities at long-term follow-up after PSGN. An uncontrolled study from north India found proteinuria (defined as more than trace levels on qualitative examination) in 13.8% of people two to 10 years after nephritis.25 Protein to creatinine ratios were > 20 mg/mmol in 9% of people recruited from a tertiary London hospital 14-22 years after sporadic childhood PSGN,26 while, in an Italian study, microalbuminuria or greater was present in 46% of 26 patients three to 24 years after PSGN but only 2.5% of 100 control participants.27 Other studies have found significantly lower renal functional reserve in people with a remote history of PSGN compared with control participants.28,29 Our study had the strengths of having a control group and a long follow-up, studying a large proportion of people in a single community and measuring albuminuria in the microalbuminuric range. Its limitations include possible misclassification of participants, as PSGN was diagnosed by clinical criteria. The abnormal urine group may have included people with subclinical PSGN, other renal disease, or isolated haematuria of no significance. However, this is unlikely to have biased results significantly, as the main findings concerned differences between the PSGN and control groups, which had more certain definitions. Nevertheless, some participants classified with PSGN may have had another cause for their renal disease. For example, one child was later diagnosed with mesangiocapillary glomerulonephritis after renal biopsy; she may have been predisposed to PSGN by pre-existing renal disease, may have had consecutive disease processes or may never have had PSGN. Lastly, control participants who were not seen during the epidemics may have had unrecognised PSGN. However, this would have decreased rather than exaggerated differences between the PSGN and control groups. Although some historical data were unavailable, fewer females than males were studied, and follow-up times varied; these factors were unlikely to have affected results. Because albuminuria precedes clinical signs of chronic renal disease, longer follow-up could be expected to show changes in blood pressure, serum creatinine levels and GFR. Other factors may be involved in the observed relationship between PSGN and albuminuria and the postulated relationship with chronic renal disease. Firstly, another underlying renal process may predispose both to PSGN on exposure to a nephritogenic streptococcus and to later albuminuria. Secondly, albuminuria may not have such adverse prognostic significance after PSGN as it does in other circumstances; our follow-up was not long enough to show progression to chronic renal disease. Thirdly, PSGN may increase risk of chronic renal disease only in combination with other insults. Renal disease is extremely common in this community, and, although our findings are likely to apply to similar populations, they may not be universally applicable. In summary, we have presented evidence that, in this community, a remote history of PSGN in childhood is a powerful risk factor for renal damage, as evidenced by increased ACR and haematuria. These findings are important as PSGN is still prevalent in children living in Aboriginal communities in Australia. Prevention of PSGN is possible through improvements to housing, economic and living conditions, along with attention to control and treatment of scabies and skin infections. Preventing PSGN may contribute to reducing the incidence of renal disease and renal failure in the future. Acknowledgements This study was supported by the National Health and Medical Research Council and the Australian Kidney Foundation. We acknowledge the support and participation of the Tiwi community and the staff of the health clinic at Nguiu. Health workers Jerome Kerinauia, Nellie Punguatji, Darren Fernando and Colleen Kantilla and project officers Eric and Elizabeth Tipiloura were key contributors to the field work. We thank Bev Hayhurst, who coordinated much of the screening program, and Zhiqiang Wang, who provided statistical advice. We also acknowledge Kate Walker's work in looking at earlier data. References Streeton CL, Hanna JN, Messer RD, Merianos A. An epidemic of acute post-streptococcal glomerulonephritis among Aboriginal children. J Paediatr Child Health 1995; 31: 245-248. Spencer JL, Silva DT, Snelling P, Hoy WE. An epidemic of renal failure among Australian Aboriginals. Med J Aust 1998; 168: 537-541. Hoy WE, Norman RJ, Hayhurst BG, Pugsley DJ. A health profile of adults in a Northern Territory aboriginal community, with an emphasis on preventable morbidities [see comments]. Aust N Z J Public Health 1997; 21: 121-126. Cass A, Gillin AG, Horvath JS. End-stage renal disease in Aboriginals in New South Wales: a very different picture to the Northern Territory. Med J Aust 1999; 171: 407-410. Perlman L, Herdman R, Kleinman H, Vernier R. Poststreptococcal glomerulonephritis. A ten year follow up of an epidemic. JAMA 1965; 194: 63-70. Potter E, Lipschultz S, Abidh S, et al. Twelve- to seventeen-year follow up of patients with poststreptococcal acute glomerulonephritis in Trinidad. N Engl J Med 1982; 307: 725-729. Garcia R, Rubio L, Rodriguez-Iturbe B. Long-term prognosis of epidemic poststreptococcal glomerulonephritis in Maracaibo: follow-up studies 11-12 years after the acute episode. Clin Nephrol 1981; 15: 291-298. Baldwin DS, Gluck MC, Schacht RG, Gallo G. The long-term course of poststreptococcal glomerulonephritis. Ann Intern Med 1974; 80: 342-358. Schacht RG, Gallo GR, Gluck MC, et al. Irreversible disease following acute poststreptococcal glomerulonephritis in children. J Chronic Dis 1979; 32: 515-524. Rodby RA, Rohde RD, Sharon Z, et al. The urine protein to creatinine ratio as a predictor of 24-hour urine protein excretion in type 1 diabetic patients with nephropathy. The Collaborative Study Group. Am J Kidney Dis 1995; 26: 904-909. Ruggenenti P, Gaspari F, Perna A, Remuzzi G. Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic renal disease in patients without diabetes [published erratum appears in BMJ 1998; 317: 1491]. BMJ 1998; 316: 504-509. Hoy WE, Mathews JD, McCredie DA, et al. The multidimensional nature of renal disease: rates and associations of albuminuria in an Australian Aboriginal community. Kidney Int 1998; 54: 1296-1304. McDonald S, Wang Z, Hoy WE. Physical and biochemical predictors of death in an Australian Aboriginal cohort. Clin Exp Pharmacol Physiol 1999; 26: 618-621. Gogna NK, Nossar V, Walker AC. Epidemic of acute poststreptococcal glomerulonephritis in aboriginal communities. Med J Aust 1983; 1: 64-66. Devanesen D, Bernard E, Stokes M, et al. Lessons from an outbreak of glomerulonephritis in an aboriginal community. Annual report 1987-88, Menzies School of Health Research. Darwin: Menzies School of Health Research, 1988. Australian Bureau of Statistics. 1996 census of population and housing: Basic community profile. Canberra: ABS, 1996. (Catalogue no. 2020.0.) Report of the Second Task Force on Blood Pressure Control in Children 1987. Task Force on Blood Pressure Control in Children. National Heart, Lung, and Blood Institute, Bethesda, Maryland. Pediatrics 1987; 79: 1-25. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41. Stata Statistical Software [program]. Release 6.0. College Station, Texas: Stata Corporation, 2000. Hoy WE. Renal disease in Australian aboriginals [editorial]. Med J Aust 1996; 165: 126-127. Hoy WE, Rees M, Kile E, et al. A new dimension to the Barker hypothesis: low birthweight and susceptibility to renal disease. Kidney Int 1999; 56: 1072-1077. Potter E, Abidh S, Sharrett R, et al. Clinical healing two to six years after poststreptococcal glomerulonephritis in Trinidad. N Engl J Med 1978; 298: 767-772. Nissenson A, Mayon-White R, Potter E, et al. Continued absence of clinical renal disease seven to 12 years after poststreptococcal acute nephritis in Trinidad. Am J Med 1979; 67: 255-262. Rodriguez-Iturbe B, Garcia R, Rubio L. Epidemic glomerulonephritis in Maracaibo. Evidence for progression to chronicity. Clin Nephrol 1976; 5: 197-205. Singhal PC, Malik GH, Narayan G, et al. Prognosis of post-streptococcal glomerulonephritis: Chandigarh study. Ann Acad Med Singapore 1982; 11: 36-41. Clark G, White RH, Glasgow EF, et al. Poststreptococcal glomerulonephritis in children: clinicopathological correlations and long-term prognosis. Pediatr Nephrol 1988; 2: 381-388. Buzio C, Allegri L, Mutti A, et al. Significance of albuminuria in the follow-up of acute poststreptococcal glomerulonephritis. Clin Nephrol 1994; 41: 259-264. Rodriguez-Iturbe B, Herrera J, Garcia R. Response to acute protein load in kidney donors and in apparently normal postacute glomerulonephritis patients: evidence for glomerular hyperfiltration. Lancet 1985; 2: 461-464. Cleper R, Davidovitz M, Halevi R, Eisenstein B. Renal functional reserve after acute poststreptococcal glomerulonephritis. Pediatr Nephrol 1997; 11: 473-476. (Received 5 Jul 2000, accepted 7 Dec 2000) Authors' details Menzies School of Health Research, Darwin, NT. Andrew V White, FRACP, Research Student, Menzies School, and Flinders University NT Clinical School, Darwin NT; currently, Paediatrician, Remote Health, Alice Springs, NT. Wendy E Hoy, FRACP, Principal Research Fellow. Royal Children's Hospital, Melbourne, VIC. David A McCredie, MD, FRACP, Nephrologist. Reprints will not be available from the authors. Correspondence: Dr A V White, Remote Health Services, PO Box 721, Alice Springs, NT 0871. Andrew. WhiteATnt.gov.au Make a comment Back to text 2: Characteristics of participants at follow-up, by diagnostic category during post-streptococcal glomerulonephritis (PSGN) epidemics PSGN (n = 63) Abnormal Control (n = 86) Urine (n = 323) P % Male 65% 45% 60% 0.02* Median age in years (range) 18.1 (8-31) 23.4 (13-32) 19.0 (10-33) 0.001† Median BMI (kg/m2) (range) 18.8 (13-45) 20.0 (15-47) 19.8 (13-40) 0.221† BMI = body mass index. * Fisher's exact test. †Kruskal-Wallis test. Back to text 3: Outcomes on follow-up screening, by diagnostic category during post-streptococcal glomerulonephritis (PSGN) epidemics Outcome PSGN (n = 63) Abnormal urine (n = 86) Control (n = 323) ACR ≥ 34 mg/mmol Rate 13% 8% 4% Crude odds ratio (95% CI) 3.8 (1.5-9.8) 2.3 (0.88-6.0) 1 Adjusted* odds ratio (95% CI) 6.1 (2.2-16.9) 1.6 (0.6-4.2) 1 PAF (95% CI) 24% (5%-40%) 8% (-14% to 26%) ACR ≥ 3.4 mg/mmol Rate 32% 30% 18% Crude odds ratio (95% CI) 2.2 (1.2-4.0) 2.0 (1.2-3.4) 1 Adjusted* odds ratio (95% CI) 3.2 (1.7-6.2) 1.4 (0.8-2.6) 1 PAF (95% CI) 11% (4%-18%) 5% (-4% to 14%) Haematuria > trace Rate 21% 9% 7% Crude odds ratio (95% CI) 3.4 (1.6-7.2) 1.4 (0.6-3.1) 1 Adjusted* odds ratio (95% CI) 3.7 (1.8-8.0) 1.1 (0.4-2.6) 1 PAF (95% CI) 20% (5%-33%) 1% (-14% to 14%) Haematuria > trace or ACR ≥ 34 mg/mmol Rate 30% 16% 11% Crude odds ratio (95% CI) 3.6 (1.9-6.8) 1.6 (0.8-3.1) 1 Adjusted* odds ratio (95% CI) 4.6 (2.3-9.0) 1.2 (0.6-2.4) 1 PAF (95% CI) 19% (8%-29%) 3% (-9% to 13%) ACR = albumin to creatinine ratio. PAF = population-attributable fraction. * Adjusted for age and sex. Back to text Back to text

Andrew V White · Wendy E Hoy · David A McCredie

Power of One A clinician with a passion for pathology Priscilla Kincaid-Smith MJA 2000; 173: 639-642 As a woman in medicine and as a scientist, Professor Kincaid-Smith has met and overcome some determined obstructionists Hammersmith and the research focus - No place for women - Analgesic nephropathy - The achievements of pathology - References - Author's details Make a comment - - - More articles on History Introduction The early 1950s, when I graduated, were an exciting time in clinical medicine. Penicillin had only just become generally available and it revolutionised the treatment of infectious disease, particularly in a hospital like Baragwanath Hospital, where I spent my early years as a doctor. This 2000-bed hospital across the road from the now-infamous Soweto township outside Johannesburg was to absorb my full attention for the next two years. It was a very exciting place for the residents and registrars, as the wards were full of very ill patients many of whom could now be cured. A dose of penicillin which we would now consider homoeopathic transformed pneumonia into an illness lasting a few days and its mortality fell dramatically. In the same years chloramphenicol did for typhoid fever what penicillin had done for pneumonia, and chloroquine cured most patients with malignant cerebral malaria. The ward balconies were full of patients with advanced tuberculosis and this too became a curable disease after streptomycin became available. Hammersmith and the research focus After three years of working like a galley slave but gaining a huge experience in clinical medicine, I was lucky enough to be accepted at Hammersmith Hospital, London. At that time Hammersmith Hospital was a leader in many fields, notably in cardiology, where McMichael and Sharply-Schafer had pioneered cardiac catheterisation and the Australian, Paul Wood, certainly one of the world's top clinical cardiologists, worked for a time. At Hammersmith the whole attitude was to do research, and improve medical knowledge. It didn't give me the same satisfaction of saving lives, but it was certainly the academic centre of London in the 1950s. At that time the ancient traditions of the London teaching hospitals were a handicap to doing new things and research. Hammersmith was frowned upon as "that hospital next to HMP Wormwood Scrubs, that hospital where they did all those experiments!". I came into contact with some of the most famous names in medicine. Each day seemed more exciting than the last and the rate of learning was exponential. I spent two and a half years in anatomical pathology, but my research interest in hypertension and the kidney stood me in good stead for my future career in the then non-existent field of nephrology. Renal biopsy was in its infancy and Robert Heptinstall, perhaps the world's best renal pathologist, came over regularly from Mary's Hospital to look at renal biopsies with our expert in this field, "Do" Doniach, who was senior pathologist at Hammersmith Hospital. This exposure to living pathology has had a great influence on my career in nephrology, which, although unequivocally clinical, has always kept me close to a microscope and involved in pathology. As a pathology registrar, I spent the mornings doing autopsies, the highlights of which were the attendance at lunchtime of all the top clinicians for a presentation of the findings. This was a no-holds-barred school, with people like John McMichael (Head of Medicine at Hammersmith) and Sheila Sherlock (who published the first major book on hepatology and became a world leader in the field). Nothing was taken for granted: the questioners were a very erudite and exacting bunch of clinicians. Histological analyses of biopsies and surgical specimens were reported on the day they became available. This necessitated many late nights to prepare for the consultant pathologist's overview the next morning, but this one-on-one learning process was excellent. As an early riser I found that I could easily start work about two hours before anyone else arrived, which allowed me to do some research. My first "kidney" paper was published in The Lancet in 1955,1 and I managed quite a lot more in those extra two hours each day. Although I was fully immersed in pathology, I couldn't drag myself away from the wards. After attending ward rounds two or three times a week, my envy of the doctors looking after patients finally drew me back to clinical medicine in 1956. My training was in cardiology -- there was no specialty of nephrology --but, as hypertension was my main research interest and most of my previous research had involved hypertension and the kidney, I became a de facto nephrologist. Another great advantage was that Malcolm Milne was second in charge in the McMichael cardiology unit in which I worked, and he was truly one of the founding fathers of nephrology. Not only did I learn a lot from Malcolm, but we ran the dialysis service for southern England and collaborated with a string of clinical fellows with renal interests, among them Bob Muehrcke (who established renal biopsy as a safe procedure) and Belding Scribner (of dialysis fame). In 1958 Sir John McMichael called me into his office to offer me a junior consultant post at Hammersmith. I was overwhelmed and greatly honoured, but had that week become engaged to Ken Fairley (from Melbourne, who spent four years training at the National Heart Hospital in cardiology with Paul Wood), and neither of us really wanted to bring up a family in England. I sometimes wonder if, had I known what awaited me in Australia, I might not have tried to persuade Ken to stay in England after all. No place for women I had assumed that I would be eligible for a similar post in Melbourne to that offered in what I regarded as the UK's top hospital, but I was very wrong. In the 1950s, in Australia, when a woman married she automatically lost her job. I was not considered for any significant post in a hospital or university in Melbourne. My curriculum vitae was not wanting: I had published several respectable articles, held a postgraduate qualification in pathology, was a member of the Royal College of Physicians, London, and had eight years of first class postgraduate training. I had excellent references. But I was the wrong sex! I was devastated. It seemed that almost all doors were closed to married women. After doing general practice locums to help pay the bills, Sir John McMichael arranged a part-time research position for me at the Baker Institute at the Alfred Hospital, Melbourne. However, Ken and I decided that if I was not wanted in Melbourne perhaps we could be of service in New Guinea, which had almost no specialists in its health service. We applied for and were offered appointments, Ken as a physician and I as a pathologist. We went up to New Guinea to inspect the new hospital in Rabaul and were thrilled with the facilities, but soon discovered that, as a married woman, my appointment could only be temporary. If any man, irrespective of qualifications, applied, he would get the position, and permanent to boot! So it was back to Melbourne, where I was appointed as an honorary physician at the Queen Victoria Hospital, a hospital run by women for women. I also had a part time research position at the Baker Institute and a part time research and teaching appointment in the University of Melbourne, Department of Medicine, at the Alfred Hospital. Eventually, in 1967, I was appointed as first Assistant in Medicine in the University of Melbourne. That was the year in which barriers to employing married women in universities were removed. Analgesic nephropathy It was on my very first day at the Alfred that I encountered my first case of what was later called analgesic nephropathy. I went, as I always had at Hammersmith Hospital, to review that day's postmortem findings. There was no formal presentation and the pathologist seemed somewhat surprised to see me. Demonstrated were the kidneys from three patients. All showed the same lesion, a kind which I had never encountered at the Hammersmith. These had very obvious features: black necrotic papillae with overlying atrophy and with striking hypertrophy in adjacent columns of Bertin (Box 1). On asking the pathologist what this lesion was he replied that it was papillary necrosis, a common complication of renal infection. "Well, it doesn't occur in renal infection in London", I replied, but I don't think he believed me. Although I recognised the lesion as the sign of a specific disease process at that first-ever autopsy attendance in Melbourne early in 1959, it took a bit longer to connect it to analgesic abuse. I had, of course, seen acute renal papillary necrosis in an occasional kidney in England, but the Alfred cases were quite different and more chronic lesions. Phenacetin nephritis had been described in Switzerland as chronic interstitial nephritis in 1953, but there was almost no mention of papillary necrosis in the description, certainly none of pigmented papillae. When I was finally able to get a photograph of one of the Swiss kidneys it was clearly different: the kidney was small and there was a moth-eaten appearance of the papillae, which presumably represented areas from which necrotic tissue had been lost (Box 2). Ken Fairley was working in Bill King's unit at the Royal Melbourne Hospital and it was he who made the connection between the kidneys seen so frequently on the autopsy table in Melbourne and analgesics. Bill King was a busy gastroenterologist and when he encountered patients with renal disease he consulted Ken. Over a relatively short period of time Ken gathered a series of patients with peptic ulcers and impaired renal function who also had a history of a phenomenally high intake of analgesics. When one of these patients passed a small fragment of pigmented material which was processed and turned out to be a piece of renal papilla the puzzle was solved. These patients had analgesic nephropathy, even if the lesions were quite different from those described by Spühler and Zollinger in Switzerland.2 In 1963, at the International Society of Nephrology meeting in Prague, we had great difficulty in persuading our European colleagues to accept our evidence for this new form of analgesic nephropathy. They particularly did not like the large kidneys, which we demonstrated to reduce in size on radiological imaging as papillae were sloughed, with resulting cortical atrophy. This always seemed to me to be the likely pathogenesis of the so-called "chronic interstitial nephritis". They objected even more strenuously to the demonstration that this shrinkage in our cases was often followed by remarkable hypertrophy in Bertin's columns. They stressed the rarity of pigmented papillae and papillary necrosis, both major features of our cases. They argued that what we were describing was certainly not "phenacetin nephritis". We were already calling it "analgesic nephropathy" by then, because it continued unabated if patients ceased taking phenacetin and replaced it with paracetamol. There was strong opposition to this view and almost a denial of any connection between our Australian variety of analgesic nephropathy and their "phenacetin nephritis" with chronic interstitial nephritis. Later, years of careful clinical documentation and animal experimentation showed that it was not the phenacetin but the mixed analgesics that caused the renal papillary necrosis. Phenacetin alone or its immediate metabolite, paracetamol, could be fed to rats in huge quantities without causing apparent damage. But when we fed rats the analgesic powders and tablets then being sold in huge quantities in Australia we quickly reproduced the lesion of renal papillary necrosis, which closely resembled analgesic nephropathy in man, even to the detail of pigmented papillae. The stories of analgesic abuse extracted from patients at that time were incredible. The patients were truly addicted to the analgesics. They appeared to be seeking the mood-altering effects, not the analgesic effects, and it seemed that it was the phenacetin which they missed when taking different combinations. The patients were commonly heavy smokers and found it easier to give up cigarettes than analgesics! In the first group of patients that we studied, as many died of coronary artery disease as of renal failure.3 Extensive premature atheroma was a prominent feature, but we could never quite prove that it was the analgesic abuse and not the smoking that was linked to the atheroma. Renal artery stenosis was another common feature, perhaps also due to smoking, but we did postulate that the huge quantities of aspirin which these patients took may have destroyed the "good" as well as the "bad" prostaglandins and predisposed to severe atheroma. Our wards were full of patients with the analgesic syndrome. In addition to the characteristic renal disease, peptic ulceration, anaemia, premature atheroma and premature ageing, dementia was a frequent finding. Some blamed phenacetin for the impaired cognitive function. Severe and often malignant hypertension was another characteristic feature. Renal failure was of course a major cause of death, but if the patient could be persuaded to give up the analgesic abuse a remarkable degree of recovery could be expected. Nonetheless, when this condition started to feature on dialysis and transplant registries 10 years later, it was indeed a major cause of end-stage renal failure -- most common in Queensland and New South Wales and least common in Victoria, where our studies had been carried out. Gradually the message got across. Long before government regulations were introduced to control sales, people became aware of the dangers of analgesic abuse and the prevalence gradually declined. Analgesic powders and tablets, which were then available free in factories and other places, also disappeared, as did the cardboard boxes in which a gross of analgesic powders or tablets were sold. They had once been a very prominent item in the weekly family supermarket trolley. Over the next 10 years or so, the pharmaceutical companies lobbied long and hard against the evidence that analgesic abuse was a major cause of renal failure. In the late 1970s I happened to be flying interstate, seated in front of two senior executives from one of the many companies whose fortunes were founded on APC sales. From this vantage point, I overheard them vigorously attacking me and what I had said about analgesic nephropathy. I was of course delighted that they thought that I had had such an influence on analgesic sales. Later, the tenor of their discussion was that Australia was a lost cause for advertisement and sale of mixed analgesics, and they began to discuss plans to invade the markets of South East Asia, where there were no controls over either advertising or sales. They were targeting Malaysia in the first instance, and reports of analgesic nephropathy from Malaysia 10-20 years later confirm that their plans succeeded. Advertising had been one of the secrets of the success of analgesic sales and this dated back to the 1920s, when Nicholas in Melbourne commenced manufacture of aspirin after the defeat of Germany in World War I and the collapse of Bayer. History relates that a new manager from the United States had predicted that there were millions to be made from aggressive advertising of analgesics. Thirty years later one would still hear on television programs that "You will need Aspro today". It was not uncommon even in the 1960s and 1970s to see shop windows devoted to advertising a particular variety of analgesics (Box 3). Between 1979 and 1982 all Australian States legislated to control over-the-counter sales of mixed analgesics. This was 20 years after most nephrologists were convinced of the need to do this. The final success came from joint activities by the Australian Kidney Foundation and the Australasian Society of Nephrology, which managed to convince the National Health and Medical Research Council and, in turn, the Government. Progress was painfully slow to those of us struggling with the very common disease which resulted from analgesic abuse. The controls were sensible and effective. Regulations controlled the number of analgesics that could be sold in one pack and did not permit the sale of combinations of aspirin, phenacetin, paracetamol and caffeine. Analgesic nephropathy, which had been such a common clinical condition, gradually faded away. The achievements of pathology Although I now rarely visit the autopsy room, I still look down the microscope every day, peering at all the fascinating things which appear in the urine of patients with renal disease, or examining renal biopsies. I now have a collection of some 20 000 renal biopsies; in many I have known the clinical story as well as the pathology. Nephrology was at first dominated by physiologists and pathology was a very poor relation, but, in my view, pathology has contributed far more to clinical nephrology than physiology. Now pathology, in combination with various immunological techniques applied to biopsy tissue, is certainly at the forefront of advancing knowledge in nephrology. References Kincaid-Smith P. Vascular obstruction in chronic pyelonephritic kidneys and its relation to hypertension. Lancet 1955; 2: 1263-1269. Spühler O, Zollinger HV. Die Chronische Interstitielle Nephritis. S Klin Med 1953; 151: 1-50. Dawborn JK, Fairley KF, Kincaid-Smith P, King WE. The association of peptic ulceration and chronic renal disease and analgesic abuse. Quart J Med 1966; 35: 69-83. Author's details Epworth Hospital, Melbourne, VIC. Priscilla Kincaid-Smith, AC, MD, FRACP, FRCPA, Medical Director and Director of Nephrology; Emeritus Professor, University of Melbourne. Reprints will not be available from the author. Correspondence: Professor P Kincaid-Smith, Epworth Medical Centre, 185-187 Hoddle Street, Richmond, VIC 3121. priscillkATepworth.org.au 1: Autopsy specimen of both kidneys and the aorta in a 43-year-old man The kidneys show bars of hypertrophy on the outer aspect of the right kidney representing hypertrophy in columns of Bertin. The cut surface of the left kidney shows typical features of analgesic nephropathy, with black pigmented papillae, atrophy of cortex over nephrotic papillae and pale areas of hypertrophy in Bertin's columns. The aorta shows extensive atheroma. Return to text 2: Cut section of a kidney with typical features of the "Swiss" variety of analgesic nephropathy The cortex is atrophic. The papillae show small cavities from which necrotic material has been lost. No hypertrophy is seen in Bertin's columns. Return to text 3: A typical 1960s shop window display advertising a popular analgesic Return to text

Priscilla Kincaid-Smith

Indigenous Health Research Reducing premature death and renal failure in Australian Aboriginals A community-based cardiovascular and renal protective program Wendy E Hoy, Philip R Baker, Angela M Kelly and Zhiqiang Wang MJA 2000; 172: 473-478 Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Aboriginal health Abstract Objective: To describe results of a systematic treatment program to modify renal and cardiovascular disease in an Aboriginal community whose rates of renal failure and cardiovascular deaths are among the highest in Australia. Design: Longitudinal survey of people during treatment, and comparison of rates of natural death and renal failure with those in a historical control group. Setting: Tiwi Islands (population, about 1800), November 1995 to December 1998. Participants: All adults with blood pressure ≥ 140/90, with diabetes and urinary albumin/creatinine ratio (ACR) ≥ 3.4 g/mol (microalbuminuria threshold), or with progressive overt albuminuria (ACR ≥ 34 g/mol) were eligible for treatment. The historical control group comprised 229 people who satisfied these criteria in the pretreatment period 1992-1995. Interventions: Perindopril, combined with calcium-channel blockers and diuretics if needed to achieve blood pressure goals; attempts to improve control of blood glucose and lipid levels; health education. Main outcome measures: Blood pressure, ACR, serum creatinine level and glomerular filtration rate (GFR) over two years of treatment; rates of renal failure and natural death compared with control group (analysed on intention-to-treat basis). Results: 258 people enrolled in the program, and 118 had complete data for two years of treatment. In these 118, blood pressures fell significantly, while ACR and GFR stabilised. Rates of the combined endpoints of renal failure and natural death per 100 person-years were 2.9 for the treatment group (95% CI, 1.7-4.6) and 4.8 for the control group (95% CI, 3.3-7.0). After adjustment for baseline ACR category, the relative risk of the treatment group versus the control group for these combined endpoints was 0.47 (95% CI, 0.25-0.86; P = 0.013). Treatment benefit was especially marked in people with overt albuminuria or hypertension and in non-diabetic people. The estimates of benefit were supported by a fall in community rates of death and renal failure. Conclusions: Aboriginal people can participate enthusiastically in chronic disease management, with rapid, dramatic improvement in clinical profiles and mortality. Similar programs should be introduced urgently into other Aboriginal communities nationwide. Aboriginal people in the Northern Territory are experiencing an epidemic of cardiovascular disease (CVD) and end-stage renal disease (ESRD). Age-standardised CVD death rates are three times those of non-Aboriginal people,1 while the incidence of treated ESRD in Aboriginal people is approaching 1000 per million, and doubling every four years.2 ESRD treatment costs, at $100 000 per person annually, are becoming a huge burden,3 but premature death is the greater human catastrophe. These problems are especially serious in the communities of the Tiwi Islands, north of Darwin (population, about 1800) (Box 1). The incidence of ESRD among Tiwi people recently reached 2700 per million, and they have one of the highest CVD mortality rates in Australia.2,4In a community-wide screening program starting in the early 1990s, we found a high prevalence of cardiovascular risk factors, including type 2 diabetes and hypertension, and albuminuria (measured by the albumin/creatinine ratio (ACR) of a random urine specimen).5 Albuminuria correlated inversely with glomerular filtration rate (GFR), and its intensity predicted not only renal failure, but also cardiovascular deaths and all-cause natural deaths.6-9 In the early 1990s, use of antihypertensive drugs was increasing gradually in the Tiwi communities, but systematic management of the huge burden of morbidity identified by the screening program was beyond the capacity of the existing health services. In November 1995, we therefore introduced a systematic treatment program to reduce blood pressure and to modify the expression and progression of renal and cardiovascular disease. We describe the results of this program to the end of 1998. Methods The study was a longitudinal survey of people in the Tiwi Islands communities during treatment, and comparison of endpoints with a historical control group. Treatment was offered to eligible people as part of improved standard care. All participants gave informed consent to have their course followed up for the projects The epidemiology and prevention of Aboriginal renal disease, Parts 1 and 2. These projects were approved by the Joint Institutional Ethics Committee of the Menzies School of Health Research and Territory Health Services, Darwin, and its Aboriginal subcommittee, and by the Tiwi Land Council (Part 1) and the Tiwi Health Board (Part 2). Treatment program The program relied considerably on screening and treatment algorithms. Interventions included education about diet, exercise, health behaviours and medical treatment. Medical treatment centred around use of a long-acting angiotensin-converting enzyme inhibitor (ACEi) (perindopril; Coversyl [Servier]), aggressive blood pressure control,10,11 and, where appropriate, oral hypoglycaemic and lipid-lowering drugs. The choice of an ACEi was based on the well recognised antihypertensive and cardiovascular-protective effects of this class of drug12 and several reports, subsequently substantiated, of an additional renal protective effect.13-23 If antihypertensive drugs had been prescribed before entry into the study, they were discontinued or tapered when perindopril was started. Objectives were to achieve a minimum daily dose of 4 mg perindopril and to lower blood pressure, initially to < 130/85, but more recently to < 120/75.10 A stepped approach to achieve these blood pressures included increasing perindopril to 8 mg, with addition of long-acting calcium-channel blockers and/or diuretics if needed. Participants were seen at least monthly while medications were introduced or changed, then at least every three months for the first year, and at least every six months thereafter. Each examination included a minimum of a brief history, medication review, and measurement of weight, blood pressure, urinary ACR and serum creatinine level and, in diabetics, evaluation of blood glucose control. After a start-up period, the day-to-day program was largely conducted by local health workers and community project officers, who were supported by telephone contacts and regular visits by nurse coordinators from Darwin. Doctors, who reviewed eligibility assessments, supported or made treatment decisions and modified the protocols, were less intensively involved. The program has run in parallel with other clinic activities in Nguiu, Bathurst Island, but has been integrated into regular clinic activities at the Melville Island communities of Milikapiti and Pirlangimpi. Participants Treatment group: People eligible for ACEi therapy were those with: hypertension (blood pressure ≥ 140/90 mmHg); diabetes and ACR ≥ 3.4 g/mol (microalbuminuria threshold), regardless of blood pressure; or progressive overt albuminuria (ACR ≥ 34 g/mol on first testing and increasing over time), regardless of blood pressure or diabetes status. All qualifying features needed to be confirmed on at least two occasions. People with past adverse reactions and breastfeeding women were ineligible for ACEi therapy. Fertile women were advised about teratogenic risks and the options of contraception or discontinuation of ACEi medication early in unplanned pregnancy. People with serum creatinine levels over 250 µmol/L were considered ineligible for long-acting ACEi therapy in the first six months of the program, but were later enrolled when treatment proved safe and effective in people with mild and moderate renal insufficiency. To some extent, enrolment was prioritised by disease severity. Thus, most people with overt albuminuria, uncontrolled blood pressure and renal insufficiency were enrolled in the first year of the program. Control group: In the absence of a parallel control group, rates of renal failure and natural death in participants were compared with those of a historical control group from the pre-program period. This control group comprised adults whose results on a single screening examination between July 1992 and September 1995 met the eligibility criteria later used for the treatment program. Selection was blinded to their future course, which was followed to 30 October 1995. Data analyses Analyses were performed using STATA statistical software.24 Clinical profiles in the treatment group were described at baseline, six, 12, and 24 months of treatment, regardless of compliance, and were compared by analysis of variance, using geometric means for ACR and serum creatinine level to normalise their distribution. All endpoint data in the treatment group were analysed on an intention-to-treat basis. Rates of natural death and renal failure were calculated by baseline ACR category for the intention-to-treat and control groups, and the risk ratios for the intention-to-treat group calculated in stratified analysis by ACR category by the Mantel-Haenszel method for cohort studies. Kaplan-Meier survival curves for both groups were derived, and survivals compared by the non-parametric Wilcoxon technique. Results Enrolment By 31 December 1998, 258 people had enrolled in the program (29% of all adults in the island communities) and 227 were still participating. Of these, 39 had completed over three years of treatment, 137 over two years, 168 over one year, and 192 over six months. Of 31 dropouts, nine had died, seven had begun dialysis (two of whom later died), seven had stopped taking the medication because of side effects (cough in four; angioedema, itching and dizziness in one each), four became normotensive without treatment, two chose to quit, one moved, and one entered palliative care with osteomyelitis of the skull. Characteristics of people who enrolled are shown in Box 2: 42% had diabetes, almost two-thirds had hypertension, with a quarter already prescribed enalapril, and almost two-thirds had overt albuminuria. Medications and participation Doses of perindopril prescribed for the 227 people participating at the end of 1998 were 2 mg (5 people; 2%), 4 mg (72; 32%), and 8 mg (150; 66%). Calcium-channel blockers were being taken by 37 people (16%), diuretics by 15 (7%), and both by 13 (6%). Participation was enthusiastic, and compliance increased over time; 65% were taking ≥ 70% of their prescribed dose (assessed by pill counts and interview), 27% were taking medicine occasionally, and 7% were taking little or no medication at the end of 1998. Two-year clinical profiles Of the 137 people who had been treated for at least two years, 118 had largely complete follow-up data and were included in the two-year profile. These 118 were well matched with participants not included in this profile for age, BMI, and blood pressure, but were more likely to have diabetes, overt albuminuria, and to have been taking prior ACEi therapy (Box 2). These differences reflected prioritisation of sicker people for early entry into the program. Two-year clinical profiles for the 118 people are shown in Box 3. Treatment was associated with a swift and sustained fall in blood pressure, as well as stabilisation of ACR and GFR. Results are presented according to participants' clinical categories at baseline in Box 4. The fall in blood pressure was marked in people with hypertension at baseline and less marked but still apparent in those who had been normotensive, as well as in those previously prescribed an ACEi. Good blood pressure responses were seen in people both with and without diabetes, those with micro- and overt albuminuria and those with "normal" and raised levels of serum creatinine. Stabilisation of ACR and GFR was seen in all clinical categories. Indeed, serum creatinine level tended to fall and GFR to rise in all categories. Baseline weight did not change (mean, 74 kg; SD, 16 kg), while mean serum potassium level rose non-significantly from 4.04 mmol/L (SD, 0.46 mmol/L) to 4.14 mmol/L (SD, 0.49 mmol/L). No one developed significant hyperkalaemia. There was no evidence that ACEi therapy accelerated progression to renal insufficiency. Comparisons with control group Two hundred and twenty-nine people qualified as controls from the pre-program period, comprising 123 people who subsequently went onto the treatment program and 106 people who did not. Reasons for not going onto the program included death, dialysis, failure to qualify on subsequent examinations, presence of exclusion criteria (eg, pregnancy, breastfeeding), declining treatment, or moving. Baseline characteristics of the control and intention-to-treat groups are compared in Box 2. The control group was younger at enrolment, had lower BMI, and included fewer people with diabetes or overt albuminuria. The control group was followed up for a total of 564 years (individual mean, 2.5 years; range, 1 month to 3.3 years) and the intention-to-treat group for 560 years (individual mean, 2.2 years; range, 2 weeks to 3.1 years). Endpoints of the two groups are compared in Box 5. The treatment group as a whole had lower rates of dialysis, natural death and the combined endpoint (dialysis or death) than the control group, although the differences were not significant. However, rates of endpoints were strongly correlated with baseline ACR category. Indeed, renal failure necessitating dialysis was confined to people with ACR ≥ 100 g/mol at baseline, and in these people the treatment group had an estimated 57% lower dialysis rate than the control group. In contrast, rates of natural death and of the combined endpoint were lower in the treatment group than in the control group for all categories of baseline overt albuminuria. After adjustment for ACR category, the treatment group had an estimated 45% lower rate of natural death and an estimated 53% lower rate of the combined endpoint. Box 6 shows estimates of the survival advantage in people with various baseline clinical profiles after adjustment for ACR category. Treatment benefit was strong in people with overt albuminuria, non-diabetic people and people with hypertension. It was less marked in diabetic or normotensive people. Survival estimates for people with overt albuminuria at baseline are shown in Box 7. Although the intention-to-treat group showed attrition during the first year (representing ESRD and deaths of seriously ill people prioritised for early entry), a survival advantage over the control group was clear by two years of the treatment program. Discussion This study found that the introduction of a systematic treatment program to the Tiwi Island communities was associated with marked improvements in blood pressure and stabilisation of renal function in people receiving treatment. These changes contrasted sharply with the increase in blood pressure and ACR and fall in GFR noted previously in people matched for ACR category in the pretreatment status quo.10 The treatment program was also associated with a swift and dramatic decrease in rates of renal failure and natural death in the treated group compared with a historical control group, suggesting that the program prevented or at least delayed these outcomes. Further evidence for the existence of this estimated survival benefit was the decrease in community-wide rates of ESRD and natural death -- previously increasing -- after introduction of the program (Box 8). In contrast, ESRD continued to increase among non-Tiwi Aboriginal people in the Top End (Box 9), arguing against a chance background effect. Preliminary estimates of cost effectiveness of the program, based solely on avoidance or delay of dialysis, are already startling.3,25 These results show that Aboriginal people are interested in health issues and receptive to health messages, and will take medications over the long term to protect against future health risk, with excellent response. They also show that a systematic approach, with testing and treatment algorithms and clear goals, is superior to the previous approach of gradually improving medical management. While we cannot apportion relative benefit to individual elements of the treatment program, the observed fall in blood pressures alone would be expected to markedly reduce cardiovascular deaths and progression of renal disease,10,11 compatible with the effects we found. Our intention-to-treat analyses probably underestimate the therapeutic efficacy of treatment, as a third of the intention-to-treat group took the prescribed medications only occasionally or not at all. Use of the historical control group was also a potential source of bias. On the one hand, it may have also led to underestimates of treatment benefit because of the group's potentially better survival prospects, based on its younger mean age, milder disease and the probable inclusion of people with borderline blood pressure or ACR readings, as eligibility for the group was not confirmed by a second examination. On the other hand, the 123 controls who subsequently entered the treatment program might have had superior survival characteristics to the controls who did not enter the program, potentially inflating the apparent benefit of the program. Another source of bias was the prioritisation of the sickest people for early enrolment in the treatment program, many of whom were failing previous management regimens. This predisposes to poor short term outcomes of the program and underestimates of its benefits. Analyses of program results at four and five years, when more people have passed through one to two years of treatment, will dilute the impact of these early events. Longer-term analyses will also be needed to evaluate any survival effect of treatment in people without overt albuminuria, and the extent to which treatment has delayed rather than prevented ESRD and death in people with overt albuminuria. The program could still be improved. Blood pressure control should be better; at two-year follow-up, 31% of people had blood pressures ≥ 140/90, and 50% had blood pressures ≥ 120/75.10 Hypertension, and therefore eligibility for treatment even in the absence of albuminuria, should probably be redefined as blood pressures ≥ 130/80 in this high-risk population.10 Control of blood glucose and lipid levels needs to improve. Finally, we might reassess the notions of the maximally renal-protective dose of ACEi and/or add other renal-protective drugs, such as angiotensin II receptor blocking agents,26,27 for poor responders. Much of the success of this particular program derives from a strong sense of community ownership and control, a non-judgemental, non-authoritarian style, and respect for competing personal and community perspectives and priorities. Individuals appreciate personalisation of their health goals, and many are slowly adopting lifestyle changes. This program is now being integrated into normal clinic activities at Nguiu. Its protocols have also been incorporated into standard care guidelines for Aboriginal adults in the Top End of the NT.28 Extension of its principles to other Aboriginal communities with high burdens of disease nationwide is a matter of urgency.29 Allocation of adequate resources is a challenge, but the clinical benefit and cost-effectiveness mandate the short- and intermediate-term investment. Acknowledgements This study was supported by Servier Australia, the Australian Kidney Foundation, Rio Tinto, the National Health and Medical Research Council, the Stanley Tipiloura Fund, and Territory Health Services. We gratefully acknowledge the support, enthusiasm and participation of the Tiwi community and the staff of the Tiwi Island clinics at Nguiu, Milikapiti and Pirlangimpi. We especially thank the Tiwi Health Board for review of this manuscript, and Treatment Program Coordinators Susan Jacups and Kiernan McKendry, Aboriginal Health Workers Jerome Kerinauia and Nellie Punguatji, and Community Project Officers Eric Tipiloura and Elizabeth Tipiloura for their dedicated work. Finally, we thank Resident Medical Officer, Dr Chris Harrison, for his support and participation. Dr Alan Cass updated the Top End ESRD rates. References Cunningham J, Condon J. Premature mortality in Aboriginal adults in the Northern Territory. Med J Aust 1996; 165: 309-312. Spencer JS, Silva D, Hoy WE. An epidemic of renal failure among Australian Aborigines. Med J Aust 1998; 168: 537-541. You J, Hoy W, Beaver C, Zhao Y. Costs of hemodialysis and hospitalisations for patients with end stage renal disease in the Top End of the Northern Territory. Presented at the 35th Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology; 1999 Mar 3-5; Brisbane (Qld). Jain SK, editor. Trends in mortality by causes of death in Australia, the States and Territories during 1971-1992, and in statistical subdivisions during 1991-1992. Canberra: National Center for Epidemiology and Population Health and Australian Bureau of Statistics, 1994. (ABS catalogue no. 3313.0)Hoy WE, Pugsley DJ, Normal RJ, Hayhurst BG. A brief heath profile of adults in a Northern Territory Aboriginal community: with an emphasis on preventable morbidities. Aust N Z J Public Health 1997; 21: 121-126. Hoy WE, Mathews JD, Pugsley DJ, et al. The multidimensional nature of renal disease: rates and associations of albuminuria in a high risk Aboriginal community. Kidney Int 1998; 54: 1296-1304. Cockcroft D, Gault MK. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41. Hoy WE, Wang Z, Baker P, et al. The natural history of renal disease in an Australian Aboriginal community. Presented at the 35th Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology; 1999 Mar 3-5; Brisbane (Qld). McDonald S, Wang Z, Hoy WE. Physical and biochemical predictors of death in an Australian Aboriginal cohort. Clin Exp Pharmacol Physiol 1999; 26: 618-621. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI). Arch Intern Med 1997; 157: 2413-2446. Collins R, Peto R, MacMahon S. Blood pressure, stroke and coronary artery disease. Part 2. Short term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827-838. Lonn EM, Yusuf S, Jha P. Emerging role of angiotensin converting enzyme inhibitors in cardiac and vascular protection. Circulation 1994; 90: 2056-2068. Mogensen CE. Angiotensin converting enzyme inhibitors and diabetic nephropathy. BMJ 1992; 304: 327-328. Ravid M, Savin H, Lang R, et al. Proteinuria, renal impairment, metabolic control, and blood pressure in type 2 diabetes mellitus. A 14-year follow up report on 195 patients. Arch Intern Med 1992; 152: 1225-1229. Ravid M, Savin H, Jutrin I, et al. Long term stabilizing effect of angiotensin converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type 2 diabetic patients. Ann Intern Med 1993; 118: 577-581. Gansevoort RT, de Zeeuw D, de Jong PE. Long term benefits of the antiproteinuric effect of angiotensin converting enzyme inhibition in nondiabetic renal disease. Am J Kidney Dis 1993; 22: 202-206. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin converting enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329: 1456-1462. Bedogna V, Valvo E, Casagrande P, et al. Effect of ACE inhibition in normotensive patients with chronic glomerular disease and normal renal function. Kidney Int 1994; 38: 101-107. Cattran DC, Greenwood C, Ritchie S. Long term benefits of angiotensin converting enzyme inhibitor therapy in patients with severe immunoglobulin A nephopathy: a comparison to patients receiving treatment with other antihypertensive agents and patients receiving no therapy. Am J Kidney Dis 1994; 23: 247-254. Mogensen CE, Keane WF, Bennett PH, et al. Prevention of diabetic renal disease with special reference to microalbuminuria. Lancet 1995; 346: 1080-1084. Maschio G, Alberti D, Janin G, et al. Effect of angiotensin converting enzyme inhibitor benazapril on the progression of chronic renal insufficiency. N Engl J Med 1996; 334: 939-945. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, nondiabetic nephropathy. Lancet 1997; 349: 1857-1863. Ruggenenti P, Perna A, Gheradi G, et al. Renoprotective properties of ACE inhibition in nondiabetic nonnephrotic proteinuria. Lancet 1999; 354: 359-364. Statcorp. Stata statistical software, release 6.0. College Station (TX): Stata Corporation, 1999. Baker P, Hoy WE, Wang Z, et al. Towards evaluation of the cost-effectiveness of a treatment program for renal disease in Australian Aborigines. Presented at the 35th Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology; 1999 Mar 3-5; Brisbane (Qld). Mackenzie HS, Ziai F, Omer SA, et al. Angiotensin receptor blockers in chronic renal disease: the promise of a bright future. J Amer Soc Nephrol 1999; 10 Suppl 12: S283-S286. Mimran A, Ribstein J. Angiotensin receptor blockers: pharmacology and clinical significance. J Amer Soc Nephrol 1999; 10 Suppl 12: S273-S277. Hoy WE. Screening and treatment for renal disease: the community model. Nephrology 1998; 4 Suppl iii-iv: S90-S95. Minutes of the Inaugural Meeting of the National Aboriginal and Torres Strait Islander Renal Disease Scientific Working Group and its Guidelines Subcommittee. Office of Aboriginal and Torres Strait Islander Health. 1999; Nov 16 Alice Springs (NT). (Received 14 Jul 1999, accepted 6 Apr 2000) Authors' details Menzies School of Health Research, Darwin, NT. Wendy E Hoy, FRACP, Senior Renal Consultant; Philip R Baker, BSc, NHMRC PhD Student, Menzies School of Health Research, and Department of Social and Preventive Medicine, University of Queensland, Brisbane, QLD; Angela M Kelly, RN, BAppSc, Senior Program Coordinator; Zhiqiang Wang, PhD, Epidemiologist and Statistician, and Senior Research Officer. Reprints will not be available from the authors. Correspondence: Dr W E Hoy, Menzies School of Health Research, PO Box 41096, Casuarina, NT, 0811. wendyATmenzies.su.edu.au Make a comment Back to text 2: Baseline characteristics of participants in the treatment program and the historical control group All participantsIncluded in 2-year profiles Historical control group (n=258)Yes (n=118)No* (n=140)(n=229)P?% Men43%47%40%51%0.13Mean age in years (SD)43.4 (11.1)43.5 (10.4)43.4 (11.7)40.8 (12.8)0.02Mean body mass index27.0 (5.7)27.1 (5.7)27.0 (5.8)25.2 (5.4)< 0.001(kg/m2) (SD) Blood pressure (mm Hg) Mean systolic (SD)135 (20)135 (20)135 (21)134 (20)0.58Mean diastolic (SD)82 (14)81 (13)82 (15)85 (15)0.01% With hypertension?65%66%63%65%0.91% With diabetes42%46%37%26%0.001% With ACR ≥34g/mol65%74%58%58%0.02% With raised serum creatinine level§12%13%11%12%0.62Previous ACEi25%33%16%NR ACR=urinary albumin/creatinine ratio. ACEi=angiotensin-converting enzyme inhibitor. NR=no result. *90 had been enrolled less than 2 years, 19 had been enrolled ≥ 2 years but did not have complete data for all visits, and 31 had dropped out. ?For test of significance of difference between all participants (intention-to-treat group) and control group. ?Blood pressure ≥140/90 or taking antihypertensive treatment. §Serum creatinine level > 106µmol/L (women), > 120µmol/L (men). Back to text 3: Clinical profiles over two years of treatment in 118 Tiwi people VariableBaseline6 months12 months24 monthsP*Blood pressure (mm Hg) Mean systolic (SD)135 (20)126 (21)124 (20)122 (22)< 0.001Mean diastolic (SD)81 (13)75 (14)77 (14)74 (14)< 0.001Mean? ACR (g/mol) (95% CI)55 (43-70)50 (39-64)53 (41-69)55 (43-69)0.36Mean? serum creatinine level (µmol/L) (95% CI)89 (85-93)88 (84-92)88 (84-92)84 (79-89)0.44Mean GFR (mL/min/1.73m2) (SD)89 (26)91 (28)89 (26)93 (29)0.54ACR=urinary albumin/creatinine ratio. GFR=glomerular filtration rate. *Test for significance of difference in values among the four intervals by analysis of variance. ?Geometric mean. Back to text 4: Clinical profiles over two years of treatment in 118 Tiwi people, by clinical category at baseline Blood pressure PreviousDiabetes < 140/90 (n=69)≥ 140/90 (n=49)ACEi (n=39)No (n=64)Yes (n=54)BP (mm Hg) Mean systolicBaseline123 (11)152 (17)136 (19)135 (21)136 (19)(SD)24 months117 (20)130 (22)128 (23)122 (15)122 (23)Mean diastolicBaseline75 (9)90 (12)83 (11)81 (15)81 (10)(SD)24 months72 (14)77 (13)78 (14)76 (15)72 (11)Mean ACRBaseline66 (50-87)43 (27-61)62 (40-97)48 (34-68)62 (45-91)(g/mol) (95% CI)24 months75 (57-98)35 (23-54)66 (45-98)50 (36-70)60 (41-87)Mean serumBaseline88 (82-94)90 (85-95)94 (85-103)90 (85-95)87 (81-93)creatinine level (µmol/L) (95% CI)24 months84 (77-92)84 (77-91)93 (82-105)83 (77-89)86 (78-94)Mean GFR (SD)Baseline91 (29)86 (21)91 (31)90 (26)88 (26)(mL/min/1.73m2)24 months95 (32)91 (25)92 (32)96 (28)90 (24) Albuminuria Serum creatinine level Micro-* (n=28)Overt? (n=86)Normal (n=98§)Raised? (n=15§)BP (mm Hg)Mean systolicBaseline 134 (24)135 (18)135 (20)139 (19)(SD)24 months 123 (23)120 (21)123 (22)118 (20)Mean diastolicBaseline 82 (15)81 (12)82 (13)78 (13)(SD)24 months 73 (15)74 (14)75 (14)71 (13)Mean ¶ ACRBaseline 16 (13-19)104 (90-121)49 (38-65)125 (83-187)(g/mol) (95% CI)24 months 19 (15-25)90 (72-112)50 (38-66)88 (45-174)Mean¶ serumBaseline 85 (79-92)90 (85-95)83 (82-88)137 (123-153)creatinine level (µmol/L) (95% CI)24 months 75 (70-81)88 (82-95)78 (75-81)119 (98-144)Mean GFR (SD)Baseline 88 (23)89 (28)95 (23)55 (18)(mL/min/1.73m2)24 months 102 (24)91 (28)99 (24)57 (30) ACEi=angiotensin-converting enzyme inhibitor. BP=blood pressure. ACR=urinary albumin/creatinine ratio. GFR=glomerular filtration rate. *ACR, 3.4-33g/mol. ?ACR >34g/mol. ?Serum creatinine level >106µmol/L (women), >120µmol/L (men). §Data not available for all participants. ¶Geometric mean. Back to text 5: Rates of endpoints in historical control and intention-to-treat groups Historical control group (n=229) BaselineEndpointACR (g/mol)CasesPerson-yearsRate per 100 person-years (95% CI)DialysisAll ≥ 1009 9564 1201.6 (0.8-3.1) 7.5 (3.9-14.4)Natural deathAll < 34 34-99 ≥ 10018 2 9 7555 226 205 1243.2 (1.0-5.1) 0.9 (0.2-3.5) 4.4 (2.2-8.4) 5.6 (2.7-11.2)Combined (dialysis or natural death)All < 34 34-99 100-199 ≥ 20026? 2 9 6 9543 227 205 74 374.8 (3.3-7.0) 0.9 (0.2-3.5) 4.4 (2.3-8.4) 8.1 (3.6-18.0) 24.2 (12.6-46.5) Intention-to-treat group (n=258) Endpoint CasesPerson-yearsRate per 100 person-years (95% CI)Dialysis 7 7548 1971.3 (0.6-2.6) 3.6 (1.7-7.0)Natural death 11 3 3 5560 178 194 1882.0 (1.1-3.4) 1.7 (0.5-5.2) 1.5 (0.4-4.8) 2.7 (1.1-6.4)Combined (dialysis or natural death) 16 3 3 3 7549 178 193 104 732.9 (1.7-4.6) 1.7 (0.5-5.2) 1.6 (0.5-4.8) 2.9 (0.9-8.9) 9.6 (4.6-20.2) Relative risk (RR) (95% CI) Endpoint Crude*Adjusted?P (for adjusted RR)Dialysis 0.77 (0.24-2.33)0.43 (0.17-1.12)0.08Natural death 0.59 (0.25-1.31)0.55 (0.26-1.16)0.11Combined (dialysis or natural death) 0.59 (0.30-1.14)0.47 (0.25-0.86)0.01 ACR=urinary albumin/creatinine ratio. *Overall estimate for treatment group versus control group. ?Relative risk adjusted for baseline ACRcategory. ?People who underwent dialysis and later died were counted only once for the combined endpoint. Back to text 6: Estimated survival advantage for intention-to-treat versus control group, adjusted for ACR category Clinical category at baselineRelative risk (95% CI)?PAll0.47 (0.25-0.86)0.01Overt albuminuria0.36 (0.18-0.72)0.004DiabetesNo0.28 (0.09-0.93)0.02Yes0.65 (0.28-1.51)0.31HypertensionNo0.59 (0.25-1.44)0.24Yes0.38 (0.15-0.98)0.04* ACR=urinary albumin/creatinine ratio. Categories: < 3.4 3.4-33, 34-99, 100-199, ≥ 200 g/mol. ? For combined endpoints of natural death and renal failure, intention-to-treat versus control group. Back to text Back to text Back to text Back to text

Wendy E Hoy · Philip R Baker · Angela M Kelly · Zhiqiang Wang

Research End-stage renal disease in Aboriginals in New South Wales: a very different picture to the Northern Territory Alan Cass, Adrian G Gillin and John S Horvath MJA 1999; 171: 407-410 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Aboriginal health Abstract Objectives: To compare the incidence of end-stage renal disease (ESRD) among Aboriginals in New South Wales with the incidence among Aboriginals in the Northern Territory, and to compare the patterns of ESRD among Aboriginals and non-Aboriginals in NSW. Design: Secondary data analysis of information from unpublished and published Australia and New Zealand Dialysis and Transplant Registry reports. Main outcome measures: Average annual incidence of ESRD (persons per million); form of renal replacement therapy; mortality at 31 March 1998; patient and graft survival one and five years after transplant. Results: Each year in NSW, 5-17 new Aboriginal patients are treated for ESRD. There was no increase in the average annual incidence of ESRD among NSW Aboriginals (118 per million in 1988-1989 and 111 per million in 1996-1997), whereas incidence in the NT increased from 255 per million to 800 per million. In NSW, ESRD was attributed to diabetes in 32% of Aboriginal patients, compared with 13% of non-Aboriginal patients (P < 0.001). In NSW, Aboriginal patients were younger and more likely to be female, a pattern similar to that in the NT. The outcome of ESRD treatment is not significantly different between Aboriginals and non-Aboriginals in NSW. Conclusion: There is a different pattern of incidence of ESRD and of outcomes with treatment among Aboriginals in NSW compared with those in the NT. A possible explanation is that the lower incidence in NSW reflects less profound socioeconomic disadvantage and better access to primary and specialist care. Introduction Indigenous Australians experience high morbidity and mortality due to end-stage renal disease (ESRD). In the Northern Territory, the average annual incidence of ESRD for Aboriginals in 1988-1993 was 17.4 times that for non-Aboriginals,1 a disparity made more apparent by age adjustment.2 The number of dialysis treatments in the NT is doubling every two years.3The 30 June 1996 estimate of the Indigenous population (386 049) represented 2.1% of the total Australian population,4 but Aboriginals constitute 5% of the Australian members of the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA).5 Whether the increasing incidence and prevalence of renal disease is occurring in NSW as well as nationally and in the NT has not been well documented. The aims of our study were to document the number of new Aboriginal patients with ESRD in NSW during 1987 to 1998 and compare recent trends in incidence with national and NT data, and to compare for Aboriginal and non-Aboriginal patients in NSW: the patterns of aetiology of ESRD; the demographic characteristics at the time of being entered into ANZDATA; the outcomes for individuals who were notified to the Registry during the period 1987 to 1998; and patient and graft survival for those who received transplants during the period 1987 to 1998. Methods Information was obtained from ANZDATA Annual Reports (12 and 18-21)6-10 and unpublished data from ANZDATA. All nephrology units in Australia and New Zealand that provide dialysis or transplant services submit detailed six-monthly reports to ANZDATA. The reports give information regarding new patients accepted onto treatment programs, deaths that have occurred, and any alteration in treatment for current patients, including changing the mode of dialysis or receiving a transplant. For NSW, the NT and across Australia, we analysed: the number of Aboriginal patients entered into ANZDATA from 1987 to 1998 in NSW, the NT and across Australia; and the average annual incidence of ESRD. For NSW only, we analysed: primary renal disease diagnostic category; mean age; outcome data at 31 March 1998 for people who had been entered into ANZDATA since 1 January 1987. Outcomes were categorised as death, functioning transplant, haemodialysis, continuous ambulatory peritoneal dialysis (CAPD), and loss to follow-up or having moved interstate; causes of death, categorised into cardiac, vascular, infection, social, malignancy and other; patient survival and graft survival for transplants performed between 1 January 1987 to 31 March 1998. The average annual incidence of ESRD was calculated using Australian Bureau of Statistics (ABS) estimates and projections of the Aboriginal and Torres Strait Islander population for the years between actual Census counts. These estimates are based upon current trends in fertility and mortality and take into account an increasing propensity for people to identify themselves as being of Indigenous origin. The definition of "Aboriginality" from both data sources (ANZDATA and ABS) relies upon self-identification. Annual incidence was calculated as an average for each two-year period, as there is marked variability in the number of new patients per year, and small absolute numbers. Statistical analysis of demographic and outcome data was performed using STATA 5.0.11 A t test of means and χ2 test or Fisher's exact test of proportions were performed. Survival analysis was performed at the ANZDATA Registry. Data were provided as actuarial life-table estimates and the log rank test was performed. The data were entered into STATA 5.0 and graphed. Results Incidence Each year in NSW, 5-17 new Aboriginal patients are treated for ESRD (Table 1). The average annual incidence of ESRD among Aboriginals in NSW for the two years 1988-1989 was 118 per million. This remained substantially unchanged at 111 per million in 1996-1997. During the same period the average annual incidence of ESRD in Aboriginals across Australia increased significantly (Table 1); in the NT, the rise in incidence was more marked. The crude incidence for non-Aboriginals in NSW was 78 per million for 1993-1997, a slight rise from the 1980s due to increased acceptance for dialysis of patients over the age of 65 years. Diagnostic categories Diabetes, glomerulonephritis and hypertension are the most common primary renal diseases among Aboriginals with ESRD in NSW (Table 2). Diabetes is listed as the primary renal disease in 32% of Aboriginals, compared with 13% of non-Aboriginals (P < 0.001). Analgesic nephropathy affects a significantly greater proportion of the non-Aboriginal population, mainly among females: 28% in non-Aboriginal females, compared with 10% in Aboriginal females. No definite diagnosis was recorded for 11% of Aboriginals, compared with 5% of non-Aboriginals (P = 0.004). Demographics Significantly more Aboriginal females than males entered the ESRD program in NSW (Table 3), the reverse pattern to non-Aboriginals (P = 0.03). The Aboriginal population was younger at entry to the program and there were significantly fewer people over the age of 65 years (P < 0.001). Outcome, or patient status at 31 March 1998, was not significantly different between the groups (P = 0.59). However, no attempt at age or sex standardisation has been made in this analysis. Causes of death The differences between Aboriginals and non-Aboriginals in NSW in causes of death approach statistical significance (P = 0.07). A significantly larger proportion of Aboriginals died from cardiovascular diseases (P = 0.01). A significantly smaller proportion of deaths were due to social reasons (P = 0.02). Patient and graft survival after transplant Aboriginal patients receiving transplants in NSW during the study period were younger (Figure 1), but experienced lower patient survival and graft survival rates (Figures 2a and 2b), although these differences were not significant (Table 4). Discussion Our data show no evidence of an epidemic of renal failure among Aboriginals in NSW, although the incidence remains higher than among the non-Aboriginal population. Aboriginal patients in NSW with ESRD are on average 10 years younger than non-Aboriginal patients, more likely to be female, and more likely to have diabetes and to die of cardiovascular disease. These features are similar to those reported in the NT.2 However, in NSW, there is no significant difference in outcome between Aboriginal and non-Aboriginal patients who have been entered into the Registry since January 1987, whereas, in the NT, survival is significantly worse in Aboriginal than in non-Aboriginal patients.2 The persistently high rate of withdrawal up to 1997 of NT Aboriginal people from ESRD treatment, about 25%,3 is not present in NSW. Our results show that diabetes, glomerulonephritis and hypertension are the prominent primary causes of ESRD among NSW Aboriginals. The rise in renal failure attributed to diabetes follows a similar pattern to that noted in Aboriginals across Australia.10 The pattern of primary causes of renal disease is consistent between Aboriginal populations in different States.10 Impediments to effective and culturally appropriate service delivery to Aboriginal patients have been postulated as reasons for poor survival and high withdrawal rates from treatment.12 Therapeutic programs have typically removed people from their cultural and social support networks by requiring patients to leave their land, families and communities.13 Unlike in the NT, South Australia and Western Australia, there are few remote, non-urbanised communities in NSW; Aboriginals in NSW reside predominantly in cities and rural towns. The higher proportion of Aboriginal patients with uncertain aetiology of their ESRD is consistent with a lower renal biopsy rate, which may relate to late referral and lack of access to renal specialist services. In NSW, specialist renal services are increasingly being provided where Aboriginals live. The Statistical Local Areas with the highest proportion of Indigenous people are Brewarrina (53.1%), Central Darling (25.3%), Bourke (24.5%) and Walgett (20.4%).14 CAPD training is now occurring in some larger rural centres, and haemodialysis facilities are provided in Bourke and Brewarrina. These initiatives, which significantly reduce the dislocation of patients from their community and remove impediments to the delivery of appropriate ESRD services, may facilitate improved survival. There is a tendency towards lower patient survival and graft survival among NSW Aboriginals compared with non-Aboriginals, despite the Aboriginal graft recipients' being younger. In the NT, graft and patient survival among Aboriginals are significantly worse at one and five years than among non-Aboriginals.2 A significant difference in survival is not evident in the NSW data. The larger 95% confidence intervals in the NSW Aboriginal group are a consequence of fewer transplants being performed: 36 among Aboriginal patients, compared with 1755 among non-Aboriginal patients. These numbers do not provide sufficient power to detect a significant difference between the groups. The pattern of rapidly increasing incidence of ESRD among Aboriginals across Australia, especially in the NT, is not seen in NSW. Spencer et al argue that the increase in the NT is real, not due to ageing of the Aboriginal population or improved ascertainment.2 The reason for this difference in incidence is not clear. It may be due to differences between the populations in apparent predisposition to renal disease or to differences in the prevalence of primary causes and promoters of chronic renal disease. The epidemic of disease in the NT is not only due to an increased prevalence of diabetes. Community screening studies show a prevalence of significant proteinuria in marked excess of the prevalence of diabetes or impaired glucose tolerance.2,15 In the NT, from 1988 to 1993, the average annual incidence of ESRD not attributable to diabetes was 350 per million per year among Aboriginals.1 Lower incidence of ESRD in NSW Aboriginals may reflect less profound socioeconomic disadvantage and readier access to effective primary and specialist care. However, there may be poor ascertainment, particularly in rural areas of NSW. Further study is indicated to analyse this question. Acknowledgements The data reported here have been supplied by the Australia and New Zealand Dialysis and Transplant Registry. The interpretation of these data is the responsibility of the authors and in no way should be seen as an official policy or interpretation of the Australia and New Zealand Dialysis and Transplant Registry. Dr Alan Cass is the recipient of a postgraduate research scholarship from the Centre for Kidney Research, New Children's Hospital, Sydney. We thank Dr Wendy Hoy, who critically reviewed the manuscript, and Dr Zhiqiang Wang, who provided statistical advice. References Hoy WE, Mathews JD, Pugsley DJ. Treatment of end-stage renal disease in the Top End of the Northern Territory: 1978-93. Nephrology 1995; 1: 307-313. Hoy WE, McFarlane R, Pugsley DJ, et al. Markers for cardiovascular and renal morbidity: expectations for an intervention programme in an Australian aboriginal community. Clin Exp Pharmacol Physiol 1996; 23: S33-S37. Spencer JL, Silva DT, Snelling P, Hoy WE. An epidemic of renal failure among Australian Aboriginals. Med J Aust 1998; 168: 537-541. Australian Bureau of Statistics. Experimental estimates of the Aboriginal and Torres Strait Islander population. Canberra: ABS, 1998. (Catalogue No. 3230.0.) Disney AP. Demography and survival of patients receiving treatment for chronic renal failure in Australia and New Zealand: report on dialysis and renal transplantation treatment from the Australia and New Zealand Dialysis and Transplant Registry. Am J Kidney Dis 1995; 25: 165-175. Disney APS, Collins J, Russ GR, et al. ANZDATA Registry Report 1989. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1989. Disney APS, Collins J, Russ GR, et al. ANZDATA Registry Report 1995. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1995. Disney APS, Collins J, Russ GR, et al. ANZDATA Registry Report 1996. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1996. Disney APS, Collins J, Russ GR, et al. ANZDATA Registry Report 1997. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1997. Disney APS, Collins J, Russ GR, et al. ANZDATA Registry Report 1998. Adelaide: Australia and New Zealand Dialysis and Transplant Registry, 1998. STATA statistical software [computer program]. Version 5.0. College Station, Texas: Stata Corporation, 1997. Bennett E, Manderson L, Kelly B, Hardie I. Cultural factors in dialysis and renal transplantation among aborigines and Torres Strait Islanders in north Queensland. Aust J Public Health 1995; 19: 610-615. Willis J. Fatal attraction: do high technology treatments for end-stage renal disease benefit aboriginal patients in central Australia? Aust J Public Health 1995; 19: 603-609. Australian Bureau of Statistics. Census of population and housing -- selected social and housing characteristics for statistical local areas, New South Wales and Jervis Bay. Canberra: ABS, 1996. (Catalogue no. 2015.1.) Van Buynder PG. The epidemiology of renal disease in Aboriginal Australians [Master of Public Health thesis]. Sydney: University of Sydney, 1991. (Received 12 Feb, accepted 19 Jul, 1999) Authors' details Menzies School of Health Research, Darwin, NT. Alan Cass, MB BS, FRACP, PhD student. Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW. Adrian G Gillin, FRACP, PhD, Staff Specialist; John S Horvath, MB BS, FRACP, Professor. Reprints will not be available from the authors. Correspondence: Dr A Cass, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811. alancassATmenzies.edu.au Back to textBack to textBack to textBack to textBack to textBack to text

Alan Cass · Adrian G Gillin · John S Horvath

Kidney disease in Australian Aboriginals: time for decisive action Can governments and healthcare services in northern and central Australia afford not to get organised? MJA 1998; 168: 532-533 The continued alarming rise in incidence of renal failure in Australian Aboriginals living in the Top End of the Northern Territory (NT) is documented in this issue of the Journal by Spencer and coworkers1 from the Royal Darwin Hospital and the Menzies Institute of Health Research. Are their findings an isolated observation, why is it happening, and what should be done to address the problem? The numbers are real. The Darwin incidence and prevalence figures for endstage renal disease (ESRD) in Aboriginals are entirely consistent with figures from other Aboriginal community surveys of the Kimberley, Pilbara and Goldfields regions of Western Australia (WA). The WA Health Services Research Linked Database shows that in the past 8 years there has been a yearly rise in (age-standardised) incidence of dialysis from 67 to 819 per million in Aboriginal men, and from 130 to 758 per million in Aboriginal women. The current rates are, respectively, 12-fold and 20-fold more than the non-Aboriginal rates (Ms K Brameld, Research Officer, Department of Public Health, University of Western Australia, personal communication). Whole-of-Australia incidence data recorded by the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA Registry) also support these findings (Box), with a marked disparity increasing over time between rates for Aboriginals and non-Aboriginals, particularly in the north of Australia. The difference in ESRD rates between Aboriginal and non-Aboriginal populations, described by Spencer et al, increases after age-standardisation and is further accentuated by the non-Aboriginal population in Darwin having a lower ESRD rate (37-47 per million) than the non-Aboriginal population of the rest of Australia (62 per million in the same time period). This lower rate probably reflects the "healthy migrant worker" phenomenon, seen in other isolated cities such as Perth, with relatively low rates of chronic diseases. The increasing number of new cases over time represents a combination of better ascertainment, with the development of the Aboriginal Medical Services, greater acceptance of ESRD therapy by the Aboriginal community, as well as a probable true increase in incidence of renal disease. The trends predate the appointment of a full-time nephrologist in Darwin in 1996. Why is it happening? The problem has multiple causes. An unfortunate mix of racial predisposition is aggravated by multiple adverse environmental and metabolic factors.3 Aboriginal kidney biopsy and autopsy data from the University of Melbourne have shown a range of pathological states (diabetic, hypertensive, and proliferative), underpinned by a remarkable increase in glomerular size of up to threefold normal.4 Whether this unusual glomerular change is entirely genetic or is exacerbated by intrauterine malnutrition followed by subsequent dietary excess has yet to be resolved. The infective insults present in Aboriginal communities have been amply documented,5 with repeated bacterial infections of ears, nose, chest, skin, gut and genitourinary systems, as well as endemic intestinal parasites. Even in the absence of recognised nephritogenic organisms, systemic infection will activate glomerular proliferation, affecting mesangial cells in particular.6 It is probably the development of widespread obesity and "Syndrome X" (raised body mass index, blood pressure, blood glucose, and triglyceride levels; and insulin resistance, and disordered uric acid metabolism) that most closely parallels the renal disease epidemic.7 The background social and legal factors involved are well described:8 loss of employment after voting rights and equal-pay legislation were enacted, access to alcohol, increased welfare benefits, and availability of a high-fat, high-carbohydrate diet. It is ironic that the outstanding success in correcting malnutrition and infective disease in Aboriginal children over the past 30 years should have contributed to creating a cohort of obese adults with hypertension and diabetes.9 Alcohol has several indirect but definite adverse renal effects. Each 10 g of alcohol consumed causes a rise in blood pressure in both white10 and Aboriginal11 populations. The carbohydrate load causes obesity, increasing the risk of diabetes and subsequent diabetic nephropathy. Alcohol both stimulates intestinal production and reduces hepatic clearance of IgA, increasing the risk of IgA nephropathy. (Although this is the commonest form of chronic glomerulonephritis in the non-Aboriginal population, it accounts for only a minority of cases of renal disease in Aboriginals.) Smoking is also recognised in epidemiological surveys as an independent risk factor for renal disease.12 Both these behaviours are very common in Aboriginal communities.13 What can be done about this renal disease epidemic? Remote-area dialysis works. Although renal transplantation usually gives the best rehabilitation at the lowest cost, its application is limited by scarcity of donors (cadaveric or fit live-related), disparate tissue typing between Aboriginal and white populations, and unsuitability of some recipients because of infections or poor medication compliance. The next-best option is self-care dialysis. There is a natural and understandable cultural imperative for patients in kidney failure to wish to return to their families and homes. How to deliver dialysis in remote areas is a challenge that has been successfully met by a number of nephrology units around Australia. In Townsville, Queensland, with a semi-urbanised and relatively sophisticated Aboriginal population, a chronic ambulatory peritoneal dialysis program has been in place for over a decade (Dr P de Jersey, Nephrologist, Townsville Base Hospital, personal communication). In Western Australia, since 1989, both CAPD and self-care haemodialysis have been delivered in areas up to 3500 km away from the parent nephrology unit. This has required some innovative technical approaches (such as inline water coolers, and repressurisation pumps) and training of staff to ensure cultural sensitivity (eg, using photographic rather than written instructions, and showing respect for name avoidance after family deaths).14 These nephrology units have shown that the challenge can be met with complication rates and dialysis survival that approach and occasionally better those observed in metropolitan dialysis units treating white populations.15 While about 25% more expensive than metropolitan self-care dialysis, remote-area dialysis is still half the cost of maintaining dependent, depressed and non-compliant patients against their will in the city. However, there remain patients and areas where self-care dialysis is not practicable. Hospital dialysis units can benefit from the use of Aboriginal liaison officers to improve cultural awareness, and to limit the sense of alienation for patients. Reorganisation of renal referral patterns around geographical proximity rather than along State borders (eg, referring patients from East Kimberley to Darwin, rather than to Perth) would also reduce the extent of dislocation. Screening and intervention programs are a priority. Most of the necessary components of such programs are in place and merely require coordination for maximum efficiency and effectiveness. Chronic disease screening (diabetes, hypertension, obesity) easily lends itself to the incorporation of urinalysis for protein, which, if positive, can be followed by serum creatinine estimation. Given the high rate of medical clinic attendance in Aboriginal communities, such screening can be opportunistic, reserving targeted case finding for a select identified few.16 The prime target remains improved environmental conditions.17 Availability of healthier food choices can reduce renal injury.18 Improvements in lifestyle and medication compliance have been achieved in a sizeable proportion of communities with active programs, particularly where there is Aboriginal "ownership" of the service. Reducing the blood pressure level below 140/90 mmHg (with a target of 125/85 mmHg) can slow the rate of progression of renal disease by up to 50%.19 Further, there is a particular role for angiotensin-converting enzyme inhibitors in proteinuric renal diseases, with or without diabetes.20 The cost-benefit equation is obvious. Every year of dialysis deferred for a single patient could pay the salary of another Aboriginal health worker. Can northern and central Australia healthcare services and governments afford not to get organised? Mark A B Thomas Head, Department of Nephrology Royal Perth Hospital, WA Acknowledgements: The data reported here were supplied by the Australia and New Zealand Dialysis and Transplant Registry. The interpretation and reporting of these data are the responsibility of the author and in no way should be seen as an official policy or interpretation of the Australia and New Zealand Dialysis and Transplant Registry. Spencer J, Silva D, Snelling P, Hoy WE. An epidemic of renal failure among Australian Aboriginals. Med J Aust 1998; 168: 537-541. Disney APS, Russ GR, Walker R, Sheil AGR, editors. Twentieth report of the Australian and New Zealand Dialysis and Transplant Registry 1997. Adelaide: Queen Elizabeth Hospital, 1997. Hoy WE, Mathews JD, McCredie DA, et al. The multidimensional nature of renal disease: findings in a high risk Australian Aboriginal community. Kidney Int 1998. In press. Bertram JF, Young RJ, Seymour AE, et al. Glomerulomegaly in Australian Aborigines. Nephrology 1998. In press. Gracey M, Spargo RM, Smith P, et al. Risk factors for ill-health in a remote desert-dwelling Aboriginal community in Western Australia. Aust N Z J Med 1996; 26: 171-179. Lovett DH, Bursten SL, Gemsa D, et al. Activation of glomerular mesangial cells by gram-negative bacterial cell wall components. Am J Pathol 1988; 133: 472-484. Hoy WE. Markers for cardiovascular and renal morbidity: expectations for an intervention program in an Australian Aboriginal community. Clin Exp Pharmacol Physiol 1996; 23(Suppl 1): S33-S37. Reid J, Trompf P, editors. The health of Aboriginal Australia. Sydney: Harcourt Brace Jovanovich, 1991. O'Dea K, Trainedes K, Hopper JL, Larkins RG. Impaired glucose tolerance, hyperinsulinaemia, and hypertriglyceridaemia in Australian Aborigines from the desert. Diabetes Care 1988; 11: 23-29. Puddey IB, Beilin LJ, Vandongen R, et al. Evidence for a direct effect of alcohol consumption on blood pressure in normotensive men. A randomised controlled trial. Hypertension 1985; 7: 707-713. Smith RM, Spargo RM, King RA, et al. Risk factors for hypertension in Kimberley Aborigines. Med J Aust 1992; 156: 562-566. Orth SR, Ritz E, Schrier RW. The renal risks of smoking. Kidney Int 1997; 51: 1669-1677. Hoy WE, Norman RJ, Hayhurst BG, Pugsley DJ. A health profile of adults in a Northern Territory Aboriginal community, with an emphasis on preventable morbidities. Aust N Z J Public Health 1997; 21: 121-126. Lim C, Matthews M, Whishaw J. Self-care dialysis training for Aboriginal patients. Dial Transplantation 1994; 23: 137-139. Feutrill J, Thomas L, Lazberger J, et al. Determinants of CAPD peritonitis rates in Aboriginal and non-Aboriginal patients. Kidney Int 1996; 50: 1411. Couzos S, Murray RB. Chronic renal failure. In: Aboriginal primary health care -- an evidence-based approach. Melbourne: Oxford University Press, 1999. In press. Gracey M, Williams P, Houston S. Environmental health conditions in remote and rural Aboriginal communities in Western Australia. Aust N Z J Public Health 1997; 21: 511-518. Nath KA, Grande J, Croatt A, et al. Redox regulation of renal DNA synthesis, transforming growth factor-b1 and collagen expression. Kidney Int 1998; 53: 367-381. Zucchelli P, Zuccala A, Borghi M, et al. Long-term comparison between captopril and nifedipine in the progression of renal insufficiency. Kidney Int 1992; 42: 452-458. Ruggenenti P, Remuzzi G. Angiotensin-converting enzyme inhibitor therapy for non-diabetic progressive renal disease. Curr Opin Nephrol Hypertens 1997; 6: 489-495. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. 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Abstract Objective: To define recent trends (1993-1996) in incidence of endstage renal disease (ESRD) among Australian Aboriginal people in the Top End of the Northern Territory (NT). Design: Analysis of hospital and clinical records of the Darwin-based ESRD treatment program from 1993 to 1996 and comparison with data accumulated since 1978. Participants: All people entering the ESRD treatment program from 1978 to 1996. Main outcome measures: Number of patients treated for ESRD; their ethnicity, age and sex; comorbidities in Aboriginal patients; treatment methods and outcomes. Results: More Aboriginal people presented with ESRD between 1993 and 1996 (87) than in the previous 15 years of the program (68). The incidence of ESRD in Aboriginals reached 838 per million in 1996, and is doubling every 4 years. Aboriginal people presenting with ESRD are younger than non-Aboriginal people with ESRD, and, in contrast to non-Aboriginals, ESRD rates are higher in women than men. The numbers and proportions of Aboriginal ESRD patients who have hypertension, type 2 diabetes and cardiac disease are rising. Haemodialysis remains the most common form of treatment, and the number of dialysis treatments is doubling every 2.5 years. Only 9% of Aboriginal patients entering the program in 1993-1996 were treated with chronic ambulatory peritoneal dialysis and only 3% received transplants. Despite their younger age, survival of Aboriginal people on dialysis is low (median 3.3 years v. 6.5 years in non-Aboriginals), and graft survival after transplant is poor (37% at 5 years v. 88% in non-Aboriginals). Survival has not improved in the past 4 years, with fewer deaths from infection offset by more deaths from cardiovascular disease. Conclusions: The predicted doubling of ESRD incidence among Aboriginal people by the year 2000 will add an enormous burden to limited resources. Risk factors for renal disease underlie all the excess morbidity and mortality in NT Aboriginal adults, and arise out of accelerated lifestyle changes and socioeconomic disadvantage. Better living conditions and education, robust and integrated primary healthcare programs, and systematic screening for early renal disease and treatment of those with established disease are all matters of urgency. Introduction The high rate of endstage renal disease (ESRD) in Australian Aboriginal people is attracting increased attention.1-4 The Northern Territory (NT) faces particular challenges in dealing with this problem. It has the lowest population (179 000 people) and tax base of any Australian State, and the highest proportion of Aboriginal people (22% of the population, compared with 5%-6% for Queensland and Western Australia -- the States with the next-highest proportion). It has an area of 1 346 200 km2, and only two dialysis centres, 1500 km apart (one in Darwin and one in Alice Springs), which can scarcely accommodate the increasing numbers of Aboriginal people needing treatment. In a previous article,1 we reported the rising rates of ESRD among Aboriginal people in the Top End of the NT (Figure 1), with an average annual incidence of 440 per million from 1988 to 1993. Aboriginal patients were younger than their non-Aboriginal counterparts and, in contrast to the non-Aboriginal population, more women than men were affected. There was little use of chronic ambulatory peritoneal dialysis (CAPD), and the few transplants gave poor results. Comorbidities were high and there was a shorter survival time on treatment than in non-Aboriginal people. Tiwi people living on Bathurst and Melville islands had especially high rates of ESRD, but for other communities there were too few cases to allow calculation of population-adjusted rates. We present data for ESRD treatment in the Top End of the NT for the period 1993-1996, thus extending the period of analysed data to 19 years. The expanded data allow calculation of regional population-specific rates, and illuminate trends in diagnoses, comorbidities, treatment methods and survival. Methods Study population The total study population comprised all people entering the Top End ESRD treatment program from January 1978 to December 1996 inclusive. Our data sources were dialysis unit records and hospital files. We used Australian Bureau of Statistics aggregate and regional data from the 1987, 1991 and 1995 population censuses for the denominators for calculating ESRD rates for the 4-year intervals 1985-1988, 1989-1992, and 1993-1996.5The 1991 Aboriginal community census was used to calculate individual community rates for the three 4-year intervals. People moving to the NT from other countries or other States and becoming residents are potentially included in the census and thus the denominators. Statistical analysis We calculated age-standardised rates of ESRD with Epi-Info6 using aggregate Australian non-Aboriginal data from the 1996 Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) as the reference population.7χ2 tests with Yates' correction were used to examine differences between groups. Kaplan-Meier survival analyses were performed by SPSS for Windows,8 and the log-rank test was used to compare the differences between the groups. Results In the period 1993-1996, 104 people entered the ESRD treatment program, making a total of 214 for the period 1978-1996. Of the total, 155 (72%) were Aboriginal, and 59 (28%) were non-Aboriginal. Incidence of treated ESRD Figure 2a shows the dramatic increase in incidence of ESRD in Aboriginal people over the three 4-year periods, with an average doubling time of about 4 years. More Aboriginal people (87) presented for treatment in the 4 years 1993-1996 than in the previous 15 years of the program (68). Within this most recent 4-year period, rates have continued to rise at an average of 22% per year, peaking at 838 per million9 in 1996 (compared with 39 per million in non-Aboriginal people in the NT). With age adjustment, the 1993-1996 average annual rate represents a 15-fold increase and the 1996 rate a 21-fold increase over ESRD rates in non-Aboriginal Australians nationwide. NT rates for non-Aboriginals, which did not change over this time period, are lower than Australian aggregate rates (62 per million from 1993-1996) because the NT has a younger population. All regions of the Top End are experiencing the same phenomenon, although current rates vary. Figure 2b shows the changes in incidence in Aboriginal people in the five regions with the highest current rates. The number of Aboriginal people receiving ESRD treatment (the prevalence), including those with functioning transplants, peaked at 2871 per million in 1996 versus 377 per million for non-Aboriginals. Finally, the number of dialysis procedures (which accrue most of the costs) is rising by 28% per year, or doubling every 2.5 years.9 Sex and age distribution of ESRD patients Ninety-three (60%) of the 155 Aboriginals with ESRD were women and 62 (40%) were men, compared with 23 (39%) women and 36 (61%) men among the 59 non-Aboriginal patients. Figure 2c shows the higher ESRD rates in Aboriginal women than men at each time period, resulting, in 1993-1996, in an age-adjusted relative risk of 31 in women versus 16 in men. On average, Aboriginal people were 5 years younger than non-Aboriginal people on entering the program (44 v. 49 years). However, the age distributions were quite different, with Aboriginal people most commonly presenting between the ages of 30 and 49 years, and non-Aboriginals between 50 and 69 years. Figure 3 shows that ESRD rates in Aboriginal people rose in most age groups over the life of the program, so that the average age and age distribution did not change appreciably. The age-specific incidence of ESRD in Aboriginal people peaked at age 50-59 years, and in non-Aboriginals at over 70 years. Renal failure causes and comorbidities in Aboriginals The Table compares the distribution of "causes" of ESRD in the two most recent 4-year intervals in those patients with documented causes. The proportion of ESRD in Aboriginal people attributed to (but not always solely due to) diabetes has almost doubled, that classified as glomerulonephritis has fallen by more than half, and the proportion in the "unknown" category has increased markedly. Aboriginal people with ESRD are more likely than non-Aboriginal people to have type 2 diabetes (48% v. 24%; P = 0.002) and hypertension (52% v. 32%; P = 0.01). Furthermore, these proportions have increased recently: for diabetes from 37% pre-1993 to 60% in 1993-1996 (P < 0.005); and for hypertension from 43% to 57% (P = 0.1); and for people with both diabetes and hypertension from 19% to 38% (P = 0.011). Treatment for ESRD Fifty-one per cent (30) of non-Aboriginal people, but only 17% (26) of Aboriginal people, have received transplants since 1978, and only 3% in the period 1993-1996. Potential reasons for this discrepancy include medical ineligibility, discouraging earlier results, distance to the transplant centre (in Adelaide), underservicing and difficulties in supervision of care in remote areas, lack of living related donors, and difficulties in HLA matching with donor organs. In 1996, only 11% of Aboriginal people with ESRD had functioning transplants versus 65% for non-Aboriginal people. Chronic ambulatory peritoneal dialysis (CAPD) rates in Aboriginal patients remain low, with only 5% of incident cases pre-1993 and 9% in 1993-1996 treated in this manner. Patient and graft survival Despite the younger age of Aboriginal patients with ESRD, their "integrated" survival (with all forms of treatment, ie, dialysis and transplantation) was significantly worse than that of non-Aboriginal people, with median survival times of 3.6 versus 12.3 years (P = 0.0025). This difference was reflected in those with and without diabetes. While survival on dialysis (CAPD and haemodialysis), as shown in Figure 4, tended to be lower in Aboriginal people (median 3.3 v. 6.5 years; P = 0.34), both graft and patient survival after transplantation were clearly worse (Figures 5 and 6). Patient survival at 1 and 5 years after transplantation was 92% and 60% for Aboriginals, compared with 97% and 93% for non-Aboriginals (P < 0.001), and graft survival at 1 and 5 years was 73% and 37% for Aboriginal people, compared with 97% and 88% for non-Aboriginal people (P < 0.001). There has been no improvement in integrated survival, or in dialysis or transplant survival separately, in the period 1993-1996. Causes of death The causes of death in Aboriginal people have changed for the period 1993-1996. Deaths due to cardiac disease have increased from 33% before 1993 to 51% after 1993. Deaths due to voluntary withdrawal from treatment are unchanged (24% and 25%, respectively). In contrast, only one non-Aboriginal patient has ever withdrawn from treatment, and none in the past decade. Discussion These data for 1993-1996 confirm and further define the rise in incidence of renal failure among Aboriginal people in the Top End of the Northern Territory. No community is spared, and this pattern is repeated in Central Australian Aboriginals, who have even higher rates (1400 per million in 1996).4 Current incidence rates are now comparable with those of Afro-Americans and Native Americans (800 and 744 per million, respectively, in 1995); however, age-adjusted rates are much higher in Australian Aboriginals (due to their very youthful population) and are increasing much faster, with a doubling time less than 4 years versus 10 years for the US minority groups.10 These alarming figures are nonetheless underestimates, because some Aboriginal people, especially older people and those from very remote communities, decline treatment for ESRD or are medically unsuited. Most of the increase is real. It is not due to ageing of the Aboriginal population, as it is reflected across every age group; and it is not due to improved ascertainment, at least in the major communities, as awareness has been high since the mid 1980s. The disability and the personal, family and community disruption are great, and the resource requirement will be truly formidable if current rates of increase, which project up to 500 new cases between 1997 and 2004 (exponential progression), are sustained. The data confirm the younger age and female predominance of Aboriginal people with ESRD. The latter might be due, in part, to lower birthweights and the relatively higher adult body weights in women, with more marked insulin resistance and earlier onset of type 2 diabetes.11,12 Both occur also in Central Australia.4 Some of the change in attributed cause of ESRD over the most recent 8-year period reflects subjectivity in assignment criteria, but much reflects reassignment of the common finding of bland glomerulomegaly with absent or minimal inflammation13-15 from the "glomerulonephritis" category to the "unknown" category. The rise in renal failure attributed to diabetes is compatible with the dramatic increase in rates of diabetes and its complications in all Aboriginal communities,16 but clinical and biopsy data show that diabetes is more often a facilitating factor for disease expression and progression rather than the prime or sole cause of the underlying nephropathy.11,14 The increased incidence in all communities of Syndrome X (obesity, hypertension, dyslipidaemia, dysglycaemia and predisposition to cardiovascular disease), which is attributed to insulin resistance, likewise explains the increasing proportions of Aboriginal people presenting for ESRD treatment with diabetes and hypertension as comorbidities.11,16-18 These conditions are already generating more heart attacks, strokes, coronary angioplasties, coronary artery bypass graft procedures and cardiovascular deaths among Aboriginal ESRD patients. As the epidemic grows and the Aboriginal population ages, these complications will become more common, and further increase costs, complicate treatment and compromise survival. The persistently high rate of withdrawal of Aboriginal people from ESRD treatment reflects difficulties with chronic disability, the complex treatment regimen, and loss of social and family support and "land identity" associated with relocation from their community to Darwin for treatment.19,20 Initiatives to move treatment closer to home include attempts to promote CAPD, which has low rates of technical failure and peritonitis, but major problems with exit-site infections;20 a renewed focus on transplant (seven Aboriginal people received transplants in 1997); construction of the first community-based dialysis unit with seven stations on the Tiwi islands; and the possibility of placing haemodialysis stations in clinics in high risk remote areas. However, deliberations about efficient and equitable delivery of ESRD treatment must no longer be allowed to dominate the dialogue. Dialysis in the Top End currently costs $496 per treatment, which is about $75 000 per patient per year. This cost does not include medicines, relocation and housing, transportation and hospitalisations.9 The allocation of resources of this magnitude to people with a median life expectancy of 3.3 years must be balanced by serious and sustained community-based initiatives to prevent and ameliorate the underlying problem. Most renal disease in Aboriginal communities is marked by albuminuria, and all renal failure arises in people with a history of progressive overt albuminuria.11Risk factors for renal failure include low birthweight and infant malnutrition, infections (scabies, poststreptococcal glomerulonephritis), increasing adult weight, high blood pressure, increasing glucose levels, insulin resistance, dyslipidaemia, and heavy drinking.11 Several risk factors can operate simultaneously, progressively compounding the decline in renal function that accompanies increasing age. The current epidemic is probably explained by the confluence of many risk factors over a short time period, associated with dramatic lifestyle changes and serious socioeconomic disadvantage. Ironically, the great fall in infant mortality between the late 1950s and late 1970s, a consequence of better hospital management of sick babies, means that those low birthweight babies now surviving to adult life are at high risk for renal and other chronic diseases.11,21 This multifactorial perspective on renal disease necessitates a rethinking of renal disease classifications.11 There is a need for a stronger focus on community and individual risk factor profiles and on pathophysiological interactions, and some de-emphasis of categorical definitions. It justifies a general preventive health services model, which will also reduce the diabetes, hypertension, cardiovascular disease, chronic lung disease and infections that contribute to the excess mortality in NT Aboriginal adults.17 In addition, screening programs to recognise early and established renal disease, and treatment (including angiotensin-converting enzyme inhibitors) to arrest disease progression, must be incorporated into regular adult healthcare in every Aboriginal community as a matter of urgency.22,23 Acknowledgements This study was supported by the National Health and Medical Research Council of Australia, and the Australian Kidney Foundation. We thank Dr David Pugsley, who led the way with renal services in the Northern Territory, and established the basis of these observations, and Dr Diane Howard and Dr Sid Selva-Nayagam, who have had the longest tenure of care of renal patients. We thank the staff of the Nightcliff Dialysis Unit and the Renal Unit at Royal Darwin Hospital for their excellent care and cooperation. Dr Zhiqiang Wang assisted with statistical analyses, and Ms Susan Jacups with clerical and graphic support. References Hoy WE, Mathews JD, Pugsley DJ. Treatment of end-stage renal disease in the Top End of the Northern Territory: 1978-93. Nephrology 1995; 1: 307-313. Hoy WE, Silva D. NT Top End Aboriginal end stage renal disease data and projections. Darwin, NT: Renal Strategy Committee, Territory Health Services, February 1997. Hoy WE. Renal disease in Aboriginal Australians. Med J Aust 1996; 165: 126-127. Renal disease in Central Australia -- challenges and opportunities for better health. Health Strategies, Deakin. Melbourne: Deakin University, September, 1997. Australian Bureau of Statistics. 1996 Census of population and housing. Aboriginal community profiles, small area data. Canberra: ABS, 1996. (Catalogue No. 2020.0.) Dean AG, Dean JA, Coulombier D, et al. Epi-Info, version 6: a word processing, database and statistics program for epidemiology on microcomputers. Atlanta, Ga: Centers for Disease Control and Prevention, 1994. Disney APS, editor. ANZDATA Report 1996. Nineteenth report of the Australian and New Zealand Dialysis and Transplant Registry. Adelaide: Queen Elizabeth Hospital, 1996. SPSS -- Statistical Package for the Social Sciences [computer program], release 6.1, standard version. Chicago: SPSS Inc, 1988. Margetts C, Morris E. Cabinet submission to the NT Legislature for renal services funding. Darwin: Royal Darwin Hospital, February 1998. United States Renal Data System (USRDS). Annual Data Report. Bethesda, MD: The National Institutes of Health, NIDDK, April 1997. Hoy WE, Mathews JD, McCredie DA, et al. The multidimensional nature of renal disease: findings in a high risk Australian Aboriginal community. Kidney Int 1998. In press. Hoy WE, Norman RJ, Hayhurst B, G Pugsley DJ. 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Clin Exp Pharmacol Physiol 1996; 23 (Suppl 1), S33-S37. Hoy WE. Guidelines for screening and treatment of renal disease in Aboriginal communities. Nephrology 1998. In press. (Received 5 Jan, accepted 10 Mar, 1998) Authors' details Menzies School of Health Research, Darwin, NT. Janine L Spencer, FRACP, DTM&H(Lond), Paediatrician, Australian Kidney Foundation Research Fellow. Wendy E Hoy, BScMed, FRACP, NHMRC Senior Research Fellow, Director of Renal Program; and Renal Community Services Specialist, Territory Health Service. TVW Telethon Institute for Child Health Research, Perth, WA. Desiree T Silva, FRACP, MPH, Paediatrician. Royal Darwin Hospital, Darwin, NT. Paul Snelling, FRACP, Nephrologist, Royal Darwin Hospital, and Territory Health Service. Reprints will not be available from the authors. Correspondence: Dr W E Hoy, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811. E-mail: wendyATmenzies.su.edu.au Readers may print a single copy for personal use. 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Janine L Spencer · Desiree T Silva · Paul Snelling · Wendy E Hoy