Clinical Epidemiology of Major Nontraditional Risk Factors in Peritoneal Dialysis Patients

Abstract

End-stage renal disease (ESRD) is a situation with a cardiovascular (CV) risk profile of almost unique severity. While traditional risk factors dominate the scene in the general population, in chronic kidney disease (CKD), nontraditional risk factors play an increasingly important role, being perhaps dominant in ESRD patients. We review the role inflammation [C-reactive protein (CRP)], hyperhomocysteinemia, high plasma norepinephrine, and accumulation of the endogenous inhibitor of the nitric oxide synthase asymmetric dimethylarginine (ADMA) in the high all-cause and CV mortality of patients on continuous ambulatory peritoneal dialysis (CAPD). The association between CRP and clinical outcomes in patients on peritoneal dialysis (PD) was examined in six studies totaling 692 subjects. The largest of these studies in Caucasians indicates that the independent risk of CV events in patients in the top CRP quartile is about five times higher than in the bottom quartile. Seven prospective studies, including over 1000 hemodialysis and 176 CAPD patients, reported both positive and negative associations between homocysteine and mortality and/or CV events. Because homocysteine circulates bound to albumin, negative associations--rather than negating the vasculotoxicity of homocysteine--most likely reflect the very deleterious effects of malnutrition. Plasma norepinephrine is higher in CAPD than in hemodialysis patients, and multivariate analyses suggest the difference quantitatively entails a 16% higher risk of incident CV events. Likewise, ADMA is more elevated in CAPD patients and such an elevation corresponds to a 15% increase in risk. Nontraditional risk factors are far more prevalent in ESRD patients than in the general population. ADMA and norepinephrine may play a greater role in CV risk in CAPD than in hemodialysis patients.