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