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American Journal of Clinical Nutrition, Vol. 81, No. 6, 1257-1266, June 2005
© 2005 American Society for Clinical Nutrition


SPECIAL ARTICLE

The phenomenon of altered risk factor patterns or reverse epidemiology in persons with advanced chronic kidney failure1,2,3,4,5

Joel D Kopple

1 From the Division of Nephrology and Hypertension, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Los Angeles, CA; The David Geffen School of Medicine at the University of California, Los Angeles (UCLA); and the UCLA School of Public Health, Los Angeles, CA

This lecture reviews a recently described phenomenon in patients with advanced chronic renal failure who are undergoing maintenance hemodialysis or chronic peritoneal dialysis. The phenomenon is called risk factor reversal, reverse epidemiology, or altered risk factor patterns, and it has to do with altered relations between risk factors and the hazard ratio for morbidity or mortality in these persons. This risk factor reversal phenomenon has been reported for body weight-for-height measures, systolic and diastolic blood pressures, and serum total cholesterol, LDL-cholesterol, homocysteine, creatinine, and parathyroid hormone concentrations, as well as metabolic acidemia. These risk factors are often associated with cardiovascular morbidity or mortality and with total mortality. The relations between these risk factors and the hazard ratio for morbidity or mortality vary from major alterations from the relations found in the general population (eg, for systolic or diastolic hypertension versus the hazard ratio of mortality) to a complete, mirror-image reversal (eg, that for body mass index versus the hazard ratio of mortality). Several potential causes of altered risk factor patterns are discussed here, and it is suggested that the major cause is the confounding effects of protein-energy malnutrition and inflammatory disorders, which commonly occur in maintenance dialysis patients.

Key Words: Maintenance hemodialysis • chronic peritoneal dialysis • chronic kidney disease • chronic renal failure • paradoxical risk factors • reverse epidemiology • malnutrition • inflammation • oxidant stress • carbonyl stress




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