Volume 209 - Issue 6
When to initiate dialysis for end-stage kidney disease: evidence and challenges
Authors: Titi Chen, Vincent WS Lee and David C Harris
Med J Aust 2018; 209 (6): 275-279. || doi: 10.5694/mja18.00297
Published online: 17 September 2018
Published online: 17 September 2018
Optimal care to patients with end-stage kidney disease involves timely referral to a nephrologist and a patient-centred decision to start dialysis
Summary
- The decision about when to start dialysis for end-stage kidney disease (ESKD) is complex and is influenced by many factors. ESKD-related symptoms and signs are the most common indications for dialysis initiation. Creatinine-based formulae to estimate glomerular filtration rate (GFR) are inaccurate in patients with ESKD and, thus, the decision to start dialysis should not be based solely on estimated GFR (eGFR).
- Early dialysis initiation (ie, at an eGFR > 10 mL/min/1.73 m2) is not associated with a morbidity and mortality benefit, as shown in the Initiating Dialysis Early and Late (IDEAL) study. This observation has been incorporated into the latest guidelines, which place greater emphasis on the assessment of patients’ symptoms and signs rather than eGFR. It is suggested that in asymptomatic patients with stage 5 chronic kidney disease, dialysis may be safely delayed until the eGFR is at least as low as 5–7 mL/min/1.73 m2 if there is careful clinical follow-up and adequate patient education.
- The decision on when to start dialysis is even more challenging in older patients. Due to their comorbidities and frailty, dialysis initiation may be associated with worse outcomes and quality of life. Therefore, the decision to start dialysis in these patients should be carefully weighed against its risks, and conservative care should be considered in appropriate cases.
- To optimise the decision-making process for dialysis initiation, patients need to be referred to a nephrologist in a timely fashion to allow adequate pre-dialysis care and planning. Dialysis initiation and its timing should be a shared decision between physician, patients and family members, and should be tailored to the individual patient’s needs.
Although half a century has passed since the introduction of maintenance dialysis into clinical practice, the optimal timing of dialysis initiation is still subject to debate. The decision not only depends on clinical factors, such as patients’ renal function and symptoms and signs relating to end-stage kidney disease (ESKD) (eg, malnutrition, persistent fluid overload, profound fatigue, etc), but also psychosocial factors, including the patients’ socio-economic status, their geographic location, the attitude of the nephrologist, the perception of the patient, and the interaction between them.1 This decision is even more complex because, although dialysis can relieve a patient’s symptoms associated with ESKD and prolong life in selected patients, the therapy is associated with substantial risk and expense.
In this Narrative Review, we discuss the indications for dialysis initiation, early versus late dialysis initiation and its associated risks, the latest evidence and guidelines, special considerations in some of the high risk subgroups of patients, and strategies to optimise the decision-making process.
We identified relevant original articles and reviews published between 1990 and 2018 through PubMed, and also included the latest national and international guidelines.
Indicators and estimated glomerular filtration rate for dialysis initiation
The decision to start dialysis in patients with chronic kidney disease (CKD) often depends on the patient’s symptoms and signs related to ESKD, most of which are a result of accumulating uraemic toxins and volume overload.2 The estimated glomerular filtration rate (eGFR) at which these symptoms and signs develop varies among individuals, but severe symptoms usually do not develop until eGFR < 10 mL/min/1.73 m2.2 These symptoms and signs can be divided into absolute indications and common indications for dialysis.3 Absolute indications — which include uraemic pericarditis or pleuritis, uraemic encephalopathy and bleeding diathesis2 — are life threatening and difficult to reverse and dialysis should be initiated immediately. However, these symptoms and signs rarely occur now because dialysis is usually started before their development. Therefore, common indications for initiating dialysis include malnutrition, persistent fluid overload, profound fatigue and weakness, decreased cognitive function, refractory acidosis, hyperkalaemia and hyperphosphataemia.2
Many medical practitioners considered eGFR to be an important factor to take into account in deciding when to start dialysis. The most widely used creatinine-based formulae for estimating GFR are the CKD Epidemiology Collaboration (CKD-EPI) formula, which is currently being used in Australia, and the Modification of Diet in Renal Disease (MDRD) formula. However, these formulae have been criticised for being inaccurate in estimating renal function in patients with ESKD.4,5 This inaccuracy is due to the fact that there is large interindividual variability in creatinine levels because of factors such as muscle mass, diet, renal creatinine secretion and extra renal creatinine elimination, which are not accounted for by the formulae.6 In addition, very few patients with ESKD were included in the validation cohort.7,8 Therefore, basing the important decision of timing of dialysis initiation solely on eGFR is fraught and not recommended.
Early versus late dialysis initiation: impact on outcomes
From the 1990s to the early 2000s, there was a trend towards initiating dialysis at a progressively higher eGFR.9 In the United States, from 1995 to 2006, the percentage of patients starting dialysis when eGFR > 10 mL/min/1.73 m2 more than doubled, from 19% to 45%,10 with a similar trend observed in Australia.11 One of the reasons behind this trend in both countries is the suggestion, from early observational studies in the 1980s and 1990s, of improved outcomes in patients who started dialysis early, even before the development of uraemic symptoms and signs.12,13 It was under the perception that early initiation of dialysis would lead to improved clearance of low molecular weight solutes (eg, urea), improved nutrition and, thus, better survival.14 However, this view was disputed by studies conducted later on, which showed that early initiation of dialysis (ie, when eGFR > 10 mL/min/1.73 m2) was not associated with improved mortality, morbidity or quality of life. Some studies even showed that early initiation of dialysis was in fact associated with increased mortality.15-19 However, these were observational studies, which have inherent confounders and bias. As a result, a randomised controlled trial — discussed below — was conducted to determine whether early dialysis initiation is beneficial or harmful.20
One of the many risks of dialysis is the accelerated loss of residual renal function. This residual renal function is associated with better fluid balance and blood pressure control, improved electrolyte and haemoglobin levels, less malnutrition and inflammation and reduced atherosclerosis and vascular calcification, all of which may lead to better outcomes.21,22 Conventional thrice weekly haemodialysis is known to be associated with accelerated loss of residual renal function.23 Other risks associated with dialysis include infection,24 painful access procedures,25,26 high symptom burden and psychosocial impact, including depression and anxiety, all of which can negatively affect a patient’s quality of life.27 In fact, deterioration of health-related quality of life over time is observed in patients who undergo dialysis28 and, therefore, these risks should be carefully weighed against the potential benefits when deciding the timing of dialysis initiation. This is particularly true in high risk populations such as older patients. In addition, the limitations of dialysis should also be kept in mind. For example, dialysis cannot replace all the functions of the kidney. The average solute clearance of outpatient dialysis is much lower than that of the normal kidney, and dialysis does not provide the autoregulatory and endocrine functions of the kidney. Furthermore, dialysis cannot treat the symptoms of a systemic illness, such as lupus erythematosus, which may cause ESKD.
Optimal timing of dialysis initiation
Given the controversies surrounding the optimal timing of dialysis initiation and the limitation of previously published observational studies, a randomised control trial — the Initiating Dialysis Early and Late (IDEAL) study — in Australia and New Zealand aimed to determine whether the timing of dialysis initiation had an influence on survival.20 The study recruited 828 patients from 32 centres in Australia and New Zealand from 2000 to 2008. The participants were randomly allocated to initiate dialysis at an eGFR 10–14 mL/min/1.73 m2 (early start) or eGFR 5–7 mL/min/1.73 m2 (late start) and were followed up for a median of 3.59 years.20 The primary outcome was all-cause mortality; secondary outcomes were cardiovascular events, infections, and complications of dialysis. It was found that planned early initiation of dialysis in patients with ESKD was not associated with improved primary or secondary outcomes.20 A post hoc analysis of the IDEAL trial, using different formulae (ie, Cockcroft–Gault, MDRD and CKD-EPI), investigated the relationship between eGFR and outcomes, but no association was found.29 In addition, a companion economic study of IDEAL found that early initiation of dialysis was associated with higher costs but not improved quality of life.30 Since the IDEAL trial, a few observational studies using more sophisticated statistical methods to avoid bias and confounders, as well as those analysing subgroups of patients, also showed no benefit of initiating dialysis early.15,31-33 Therefore, in asymptomatic patients with stage 5 CKD, dialysis may be safely delayed until the eGFR is at least as low as 5–7 mL/min/1.73 m2, provided there is careful clinical follow-up.34
Before these studies, early dialysis was considered beneficial and most guidelines recommended a level of renal function at which dialysis should be considered.35 After the publication of those studies, guidelines have evolved significantly to reflect their findings. In general, most of the current guidelines suggest that the decision to start dialysis should be centred around the patient’s symptoms and signs relating to ESKD rather than eGFR.36-39 In the absence of these symptoms and signs, the lower eGFR limit by which dialysis should be considered has not been established. The guideline from Kidney Health Australia Caring for Australasians with Renal Impairment (www.cari.org.au) on timing of dialysis initiation was developed in 2005 and an update of this guideline is awaited.
The change in clinical guidelines since the publication of IDEAL and other studies has influenced clinical decision making. In the United States, before the publication of the IDEAL trial in 2010, there was an upward trend of mean eGFR at dialysis initiation from 7.7 mL/min/1.73 m2 in 1996 to 10.4 mL/min/1.73 m2 in 2009.40 However, since the publication of IDEAL, this number decreased to 9.8 mL/min/1.73 m2 in 2015.40 In Australia, the median eGFR at dialysis initiation also peaked at 7.8 mL/min/1.73 m2 in 2009 and has decreased slightly since then.11
Even though the current view is that it is safe to delay dialysis until the eGFR is at least as low as 5–7 mL/min/1.73 m2 in asymptomatic patients, a few points need to be taken into consideration. Firstly, delayed dialysis should not mean delayed preparation. Dialysis access creation, maturation and patient training all take time. In the case of haemodialysis, permanent access is ideally created a few months before dialysis initiation. If home haemodialysis is chosen, then the patient needs training and it may be necessary to perform some modifications in the home. In the case of peritoneal dialysis, even though access can be created 1–2 weeks before it can be used, patients still need to be trained, which may be difficult to achieve if dialysis is commenced too late and patients become uraemic. Secondly, technical problems with dialysis access can occur after the patient starts dialysis. This needs to be taken into consideration so that dialysis is not started too late, to allow for sufficient time to fix potential technical problems.41 Thirdly, some argue that because peritoneal dialysis is associated with better preservation of renal function, dialysis in these patients might be initiated early to help preserve this function.41
Dialysis initiation in older and other high risk patient subgroups
Older individuals constitute a growing ESKD population who may be considered for dialysis. Many of these patients have multiple comorbidities and, thus, in this subgroup, dialysis may be associated with worse outcomes. Older patients requiring dialysis have higher rates of infection-related hospitalisation and withdrawal from dialysis compared with younger patients.14 These patients have a high mortality rate, and most of them die in acute care facilities.42 Furthermore, older patients who start dialysis also have higher symptom burden and age-related problems, including falls, frailty, functional decline and cognitive impairment,43 all of which have significant negative impact on their quality of life. Moreover, these patients are less likely to receive specialist palliative care, which has been shown to improve quality of life regardless of whether they are on dialysis or not.44 In view of these considerations, there is a trend in recent years towards a greater emphasis on patients’ quality of life rather than prolonging life. For example, in December 2013, the Kidney Disease: Improving Global Outcomes Foundation held a conference on palliative care nephrology aiming to guide the development of globally applicable guidelines in this area. A detailed discussion on conservative (non-dialytic) care is beyond the scope of this manuscript. However, incorporating conservative care into the comprehensive management of older patients with ESKD is essential. In addition, the decision about dialysis initiation should also involve caregivers. As older patients requiring dialysis have more comorbidities, increased frailty and cognitive dysfunction, many are not able to perform dialysis independently or to travel to a dialysis centre themselves.45 Therefore, many patients will need caregivers to assume responsibility for their dialysis treatment. Caregiver burden in patients undergoing dialysis has increasingly been recognised in recent years.45 Given the tremendous demands placed on the caregivers, their involvement in the decision-making process is essential.
Some other high risk dialysis subgroups include paediatric patients, pregnant patients, Indigenous populations and those returning to dialysis after transplant failure. Their specific problems are summarised in the Box.
Improving care: timely referral to a nephrologist and shared decision making
CKD is a silent disease that can remain asymptomatic until it reaches an advanced stage.57 As a result, the majority of people with CKD are unaware that they have this condition, and a quarter of them present to the nephrologist with ESKD requiring dialysis within 90 days (late referrals).57 Late referrals are associated with increased morbidity, mortality and health costs and with lower quality of life.58 In the first year after dialysis initiation, the mortality rate is twice as high in patients with late referral compared with patients with early referral.59 Patients with late referral often present with a higher rate of ESKD-associated complications, such as malnutrition, severe hypertension, fluid overload, anaemia, hyperparathyroidism and hyperphosphataemia, many of which may be modifiable if the patient is referred early.60 In addition, it takes time to optimise pre-dialysis care, including deciding on dialysis modality or conservative care, access placement, education and counselling and multidisciplinary medical management, which have been shown to improve outcomes.14 Patients with late referrals would not have sufficient time to receive this optimised care, resulting in worse outcomes and in increased costs to society. Therefore, timely referral is essential for optimal care of patients with ESKD. Recommendations about the timing of nephrology referral can be found in various guidelines, such as the CKD management in general practice handbook from Kidney Health Australia,61 and are beyond the scope of this article.
Apart from the science behind decision making around dialysis initiation, there is an extra layer of complexity in the decision-making process in clinical practice. This decision also depends on the attitude of the nephrologists, the perception of the patients and the interaction between them.1 During the decision-making process, there are often tensions and differences between the physician’s and patient’s priorities and goals. Therefore, doctors need to have a greater understanding of the patient’s values and preferences and incorporate these into the decision-making process. This process should be shared between the physician, the patient and family members, and should be tailored to the individual patient’s needs.
Conclusion
Since the IDEAL trial and the subsequent observational studies, it is clear that early dialysis initiation does not always provide morbidity, mortality and quality of life benefits. In fact, it may be associated with harm in certain patient populations, especially in older patients with multiple comorbidities in whom conservative care may be preferable to dialysis. The evidence to date indicates that it is reasonable to defer the initiation of dialysis in asymptomatic patients with stage 5 CKD until eGFR is at least as low as 5–7 mL/min/1.73 m2, provided there is careful clinical follow-up and adequate patient education. To provide optimal care to patients with ESKD, they need to be referred to a nephrologist in a timely fashion and the decision to start dialysis should be patient-centred, guided by individual patient values and preferences.
Box – Specific issues in some high risk subgroups of patients requiring dialysis
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High risk patient subgroups |
Some of the issues to be considered |
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Older patients with multiple comorbidities |
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Pregnant patients |
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Indigenous patients |
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Patients with transplant failure |
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CKD = chronic kidney disease. eGFR = estimated glomerular filtration rate. ESKD = end-stage kidney disease. βhCG = β-human chorionic gonadotropin. |
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Competing interests
No relevant disclosures.
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Provenance: Not commissioned; externally peer reviewed.