Abstract
Most of the 20 million people in the US with chronic kidney disease (CKD) die before commencing dialysis. One of every five dialysis patients dies each year in the US. Although cardiovascular disease is the most common cause of death among patients with CKD, conventional cardiovascular risk factors such as hypercholesterolemia, hypertension and obesity are paradoxically associated with better survival in hemodialysis populations. Emerging data indicate the existence of this 'reverse epidemiology' in earlier stages of CKD. There are also paradoxical relationships between outcomes and race and ethnicity. For example, the survival rate of African American dialysis patients seems to be superior to that of whites on dialysis. Paradoxes-within-paradoxes have been detected among Hispanic and Asian American CKD patients. These survival paradoxes might evolve and change over the natural course of CKD progression as a result of the time differentials of competing risk factors and the overwhelming impact of malnutrition, inflammation and wasting. Reversal of the reverse epidemiology as a result of successful kidney transplantation underscores the role of nutritional status and kidney function in engendering these paradoxes. The observation of paradoxes and their reversal might lead to the formulation of new paradigms and management strategies to improve the survival of patients with CKD. Such movement away from the use of targets set on the basis of data gathered in general populations (e.g. the Framingham cohort) would be a major paradigm shift in clinical medicine and public health.
Key Points
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'Reverse epidemiology' describes a phenomenon whereby risk factors associated with adverse outcomes under one set of conditions or in one population are associated with positive outcomes under another set of conditions or in another population
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For example, higher BMI, serum cholesterol levels and systolic blood pressure are associated with increased cardiovascular risk in the general population, but with reduced morbidity and mortality in patients with stage 5 chronic kidney disease—a so-called 'survival paradox'
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Survival paradoxes associated with race have been observed in dialysis populations; for example, the mortality of African American patients is markedly lower than that of their white counterparts
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As many clinical recommendations are based on extrapolation of data from general populations, confirmation of evidence supporting reverse epidemiology in chronic disease populations could necessitate revision of guidelines
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Acknowledgements
K Kalantar-Zadeh is supported by a grant from the National Institute of Diabetes Digestive and Kidney Diseases of the National Institutes of Health (R01DK078106), a grant-in-aid from the American Heart Association, research grants from DaVita, Inc. and a philanthropist grant from Mr Harold Simmons. TB Horwich was funded by NIH training grant 401357JI30608. GC Fonarow holds the Eliot Corday Chair in Cardiovascular Medicine and Science.
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Kalantar-Zadeh, K., Kovesdy, C., Derose, S. et al. Racial and survival paradoxes in chronic kidney disease. Nat Rev Nephrol 3, 493–506 (2007). https://doi.org/10.1038/ncpneph0570
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DOI: https://doi.org/10.1038/ncpneph0570
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