Elsevier

The Lancet

Volume 383, Issue 9931, 24–30 May 2014, Pages 1831-1843
The Lancet

Series
Epidemiology, contributors to, and clinical trials of mortality risk in chronic kidney failure

https://doi.org/10.1016/S0140-6736(14)60384-6Get rights and content

Summary

Patients with chronic kidney failure—defined as a glomerular filtration rate persistently below 15 mL/min per 1·73 m2—have an unacceptably high mortality rate. In developing countries, mortality results primarily from an absence of access to renal replacement therapy. Additionally, cardiovascular and non-cardiovascular mortality are several times higher in patients on dialysis or post-renal transplantation than in the general population. Mortality of patients on renal replacement therapy is affected by a combination of socioeconomic factors, pre-existing medical disorders, renal replacement treatment modalities, and kidney failure itself. Characterisation of the key pathophysiological contributors to increased mortality and cardiorenal risk staging systems are needed for the rational design of clinical trials aimed at decreasing mortality. Policy changes to improve access to renal replacement therapy should be combined with research into low-cost renal replacement therapy and optimum clinical care, which should include multifaceted approaches simultaneously targeting several of the putative contributors to increased mortality.

Section snippets

Scope of the problem

Chronic kidney failure is defined as a glomerular filtration rate (GFR) persistently below 15 mL/min per 1·73 m2 and represents the end stage of chronic kidney disease.1 Renal replacement therapy (RRT), achieved by haemodialysis, haemodiafiltration, peritoneal dialysis, or kidney transplantation, can be lifesaving. However, mortality rates in patients on RRT are high, and in developing countries RRT is initiated in less than 25% of patients with chronic kidney failure.2 In this review, we

Epidemiology

At age 40 years, the lifetime risk of chronic kidney failure is one in 50.3 Each year about 440 000 patients worldwide start RRT, but 3 200 000 have no access to RRT and die prematurely (figure 1, appendix).1 Detailed mortality data are available only from registries in developed countries. Therefore, these data might not be representative of worldwide reality. Furthermore, information about patients with chronic kidney failure who do not receive RRT is scarce. The Global Burden of Disease 2010

Potential pathophysiological contributors

Several factors contribute to the high risk of death in chronic kidney failure (figure 3). Common risk factors for chronic kidney failure and mortality include diabetes, hypertension, overweight, atherosclerosis, lipid disorders, smoking, and possibly salt and phosphate intake.

Kidney failure results in accumulation of damaging molecules (uraemic toxins), volume overload, electrolyte abnormalities, metabolic acidosis, and neurohumoral and metabolic abnormalities that progress as renal function

Staging of mortality risk

Large observational databases, including the United States Renal Data System, the ERA-EDTA Registry, and the Dialysis Outcomes and Practice Patterns Study, have identified many hypothesis-generating risk factors for mortality in RRT (appendix). Randomised controlled trials (RCTs) should test whether interventions for these risk factors decrease mortality. Some traditional risk factors display a reverse epidemiology pattern, in which patients at both extremes of a given parameter have the

Clinical trials of mortality in chronic kidney failure

Several RCTs have addressed overall and cardiovascular mortality in chronic kidney failure. Interventions tested so far have mainly focused on drugs that might reduce the risk of atherosclerotic complications, for example, myocardial infarction and stroke. However, most cardiovascular deaths in chronic kidney failure are attributable to non-atherosclerotic complications, especially sudden death,8 which has rarely been targeted. No trials have systematically targeted non-cardiovascular mortality.

Lessons learned for early stages of chronic kidney disease and disease in the elderly

Chronic kidney disease has been generally recognised as a major cardiovascular risk factor, independent of the amount of kidney failure. The risk of death and cardiovascular risk are increased even in early stages.87, 88 Even in patients with minor kidney dysfunction—ie, stage 2 chronic kidney disease corresponding to an estimated GFR (eGFR) of 60–89 mL/min—cardiovascular outcome is worse than when the eGFR is normal. Advanced chronic kidney disease conveys an even higher risk for incident

A call to action: how to decrease worldwide mortality due to chronic kidney failure

In addition to preventing progression to chronic kidney failure, key issues to be tackled to decrease mortality due to chronic kidney failure range from optimisation of care before progression to chronic kidney failure to improvement of access to RRT. Optimisation of care before chronic kidney failure can delay the development of chronic kidney failure and ensure that patients are in the best possible clinical condition when they reach chronic kidney failure, with improved nutrition, better

Search strategy and selection criteria

We searched the Cochrane Library, Medline, Embase, and Database of Systematic Reviews (up to Nov 30, 2013). We used the search terms “mortality” or “survival” or “malnutrition” or “wasting” or “infection” or “cardiovascular” in combination with the terms “dialysis” or “end stage renal disease” or “chronic kidney disease” or “chronic kidney failure”. We mostly selected publications from the past 5 years, but did not exclude commonly referenced and highly regarded older publications. We

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