Most of the 20 million Americans with chronic kidney disease (CKD) die before commencing dialysis. One of every five dialysis patients dies each year in the United States. Although cardiovascular disease is the most common cause of death in CKD, conventional cardiovascular risk factors such as hypercholesterolemia, hypertension and obesity are paradoxically associated with better survival at least consistently in hemodialysis patients. Emerging data indicate the existence of this ‘reverse epidemiology’ even in earlier stages of CKD. These survival paradoxes might evolve progressively over the natural course of CKD as a result of time differential of the competing risk factors and the overwhelming contribution of malnutrition, inflammation and wasting. Reversal of the reverse epidemiology upon successful kidney transplantation underscores the role of nutritional status and kidney function in engendering these paradoxes. These observations, if indicative of biologically plausible and causal associations, may lead to emergence of new paradigms and potential management strategies to improve survival in CKD patients. Such movement away from use of targets derived from general populations (e.g. Framingham) would represent a major paradigm shift in clinical medicine and public health.
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