Public health

Urology
Volume 194 - Issue 5

World Kidney Day 2011: protect your kidneys, save your heart

Authors:  William G Couser and Miguel C Riella, for the Joint International Society of Nephrology and International Federation of Kidney Foundations World Kidney Day 2011 Steering Committee*

Med J Aust 2011; 194 (5): 225-227. || doi: 10.5694/j.1326-5377.2011.tb02949.x
Published online: 7 March 2011
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Early detection and prevention of kidney disease reduces the risk of cardiovascular disease. This official World Kidney Day 2011 editorial is being published concurrently in many medical journals around the world.

Protect your kidneys, save your heart

Cardiovascular disease (CVD) is the most common of the chronic non-communicable diseases that affect global mortality. About 30% of all deaths worldwide and 10% of all healthy life lost to disease are accounted for by CVD alone.1 Although there has been some decline in mortality from CVD in developed countries, no such decline has been reported in developing countries, ethnic and socially disadvantaged minority populations, or in people with accompanying chronic kidney disease (CKD).2,3

The presence of CKD significantly increases the risk of a cardiovascular event in patients with diabetes or hypertension.4,5 However, less well appreciated is that CKD alone is a strong risk factor for CVD, independent of diabetes, hypertension or any other conventional CVD risk factor.6,7 This is especially true when an increase in proteinuria, a major target of any CKD screening program, is present.6-9

The 20–30-fold increase in CVD in patients with end-stage renal disease (ESRD) has long been recognised. However, the association between lesser degrees of renal functional impairment and increased risk of CVD was definitively demonstrated only in 2004, when a community-based study of over 1000 individuals reported an independent and graded association between glomerular filtration rate (GFR) and risk of death, cardiovascular events and hospitalisations.6

Is this dramatic increase in CVD risk associated with CKD really due to CKD or does it just reflect the coexistent diabetes or hypertension present in a majority of these patients? The independent effect of CKD alone has now been well documented in many studies.7 The risk of cardiac death is increased by 46% in people with a GFR of 30–60 mL/min (stage 3 CKD) independent of traditional cardiovascular risk factors including diabetes and hypertension.10 The increased risk of cardiovascular events and mortality in people aged over 55 years with CKD alone is equivalent to, or even higher than, that seen in patients with diabetes or previous myocardial infarctions.11 Both general6,12 and high-risk populations13,14 exhibit an increased risk of CVD with CKD. This increased risk of CVD is not confined to the elderly — in volunteers with an average age of 45 years, the risk of myocardial infarction, stroke and all-cause mortality doubled in those with CKD.14

Proteinuria and cardiovascular risk

In considering the value of recommending screening for CKD along with screening for conventional CVD risk factors in selected individuals, data showing that the risk of CVD is better correlated with proteinuria (albuminuria) than with GFR alone are particularly relevant because proteinuria is virtually always a marker of kidney disease and is not a conventional CVD risk factor.6,8,9,15

Proteinuria has been shown to be a predictor of later CVD. The Prevention of Renal and Vascular Endstage Disease study showed a direct linear relationship between albuminuria and risk of cardiovascular death in the general population, even at levels of albumin excretion generally considered to be within the “normal” range (15–29 mg/day). The risk was increased more than sixfold when albumin excretion exceeded 300 mg/day.8

Recent data from the US National Health and Nutrition Examination Survey database as well as from Japan document an independent effect of albuminuria on risk of both CVD and all-cause mortality at any GFR.15,16 In patients with congestive heart failure but without diabetes, hypertension or reduced GFR, increased urinary albumin predicts both cardiovascular and all-cause mortality.17 In patients with coronary disease or previous myocardial infarctions, proteinuria confers a greater risk of mortality than reduced GFR, although both adversely influence outcomes.18

Not only the likelihood but also the time to development of a cardiovascular event is accelerated significantly by the presence of proteinuria at any GFR.19 About 78% of non-diabetic subjects with normal serum creatinine levels undergoing percutaneous coronary interventions have demonstrable CKD when screened more stringently for renal function (estimated GFR, urinary protein).20 As well as being a likely factor in accelerating development of coronary disease in these patients, the presence of CKD has been associated with an increase in other risks, including haemorrhagic complications, contrast nephropathy, re-stenosis, and death.10 Thus, multiple studies now confirm that proteinuria is a graded risk factor for CVD independent of GFR, hypertension and diabetes, and that this risk extends down into ranges of albumin excretion generally considered “normal”.21,22 Moreover, this increased cardiovascular risk has been well demonstrated in several studies where only dipsticks were used to screen for increased protein excretion.6,18,23

Although there has been concern that CKD diagnosed by reduced GFR alone identifies predominantly older adults at increased risk because of age alone,24 the connection between proteinuria as an independent risk factor for cardiovascular mortality has been confirmed by meta-analysis of 22 separate, general population, cohort studies and in both older (> 65 years of age) and younger (< 65 years of age) people of several nationalities and racial groups.23

Can treatment of CKD reduce CVD?

Finally, and most importantly from a clinical perspective, there are provocative data to suggest that renal-targeted interventions designed to reduce proteinuria and slow progression of CKD can reduce CVD risk as well. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers are of documented benefit in slowing progression of established diabetic and non-diabetic CKD.25-29 The incidence of CVD in patients with CKD is significantly higher than in patients without CKD, with more rapid reduction of GFR independent of other risk factors, suggesting that interventions that slow progression of CKD may also reduce CVD.19 A 44% reduction in cardiovascular mortality over 4 years has been reported in patients from a general population who were screened and showed no cardiovascular risk factors except increased albumin in the urine, for which they were treated with renal-targeted ACE-inhibitor therapy.30 This effect was seen primarily in people with albumin excretion rates > 50 mg/day in a pilot study, and the intervention was shown to be cost-effective in that population.31 Cardiovascular endpoints were significantly reduced in direct proportion to the reduction of albuminuria with ACE-inhibitor therapy, and albuminuria proved to be the only predictor of cardiovascular outcome.32 Other studies have also demonstrated that changes in proteinuria in people with diabetes better predict cardiovascular outcomes than changes in blood pressure achieved with ACE-inhibitor therapy.33 The potential benefit of renal-targeted therapies has recently been highlighted by observations that doses of renin-angiotensin system blockers that are higher than those required for blood pressure control alone can further reduce proteinuria independent of their effects on blood pressure or GFR.34 Restricting salt intake and adding diuretics, both very inexpensive interventions, have also been found to further enhance the proteinuria-reducing effect of renin-angiotensin system blockade.35 Data are not yet available to establish whether screening for CKD and subsequent interventions will reduce cardiovascular mortality and be cost-effective in people younger than 55 years of age.36 However, it is now known that albuminuria is a better predictor of renal and cardiovascular events than blood pressure alone, that reducing proteinuria confers more renal and cardiovascular protection than lowering blood pressure alone, and that identification of CKD can improve cardiovascular outcomes.

As celebrations of the sixth World Kidney Day approach, it is worth noting that before the past decade, kidney disease was seen by most government and public health authorities as largely confined to patients with ESRD — thankfully, a rare condition because the enormous cost of renal replacement therapy disproportionately consumes scarce health care resources and is well beyond the means of countries inhabited by over 80% of the world’s population.37,38 Much has changed. We now appreciate that kidney disease is not rare — some 10% of the population has evidence of renal dysfunction. And we know these individuals are not of concern just because a few will progress to ESRD, but more because they carry a greatly enhanced risk of premature death from CVD, the single largest and most expensive health care threat we confront at a global level.1 Just as progress is being made in treating most of the traditional cardiovascular risk factors, CKD has emerged as yet another one that independently causes substantial vascular toxicity. Fortunately, there is good news as well. Biomarkers of CKD (proteinuria, estimated GFR) are easy and relatively inexpensive to detect or estimate, and one of these, proteinuria, emerges early in the evolution of generalised vascular disease. Thus, kidney-targeted detection and prevention programs seem to offer a valuable opportunity to institute early preventive measures that go beyond traditional cardioprotective approaches. There is now compelling evidence that including selective screening for CKD in global health programs designed primarily to reduce CVD will significantly improve the outcomes of not only renal disease but especially the non-communicable diseases like diabetes and CVD that dominate future health care strategies. Roadmaps for accomplishing this have already been presented for both developed39,40 and emerging1,41 countries. However, effective implementation of such strategies will only come when both the general public and the renal community work together to convince health authorities that it is in the public interest to do this. It is our sincere hope that worldwide celebration of World Kidney Day 2011 will provide an opportunity to reinforce the message that kidney disease is indeed common, harmful and treatable, and that protecting your kidneys is an important health strategy that may save your heart.

Authors

  • William G Couser MD1
  • Miguel C Riella MD, PhD, FACP2
  • 1. International Society of Nephrology, Brussels, Belgium.
  • 2. International Federation of Kidney Foundations, Bussum, Netherlands.

Correspondence: smartin@isn-online.org

Competing interests

William Couser has received consultancy payments from Questcor and speaker fees from the American Society of Nephrology.

Acknowledgements

* Members of the Joint International Society of Nephrology (ISN) and International Federation of Kidney Foundations (IFKF) World Kidney Day 2011 Steering Committee: Willliam G Couser (ISN), Miguel C Riella (IFKF) (co-chairs); Georgi Abraham, Paul Beerkens, John Feehally, Guillermo Garcia Garcia, Jan Lantik, Dan Larsen, Philip Li, Mark Murphy and Bernardo Rodriguez-Iturbe.

References

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