HDCN Abstract:  ASN Annual Meeting -- San Diego  

Meijers B, Claes K, Bammens B, et al.

P-Cresol Free Serum Concentrations Independently Predict Cardiovascular Disease in Early Stages of CKD.

ASN Annual Meeting -- San Diego
J Am Soc Nephrol (Nov) 20:371A 2009

Introduction: Cardiovascular disease is a leading cause of death in chronic kidney disease. Free serum levels of the protein bound uremic retention solute p-cresol are associated with cardiovascular disease in hemodialysis patients. The relation between p-cresol and cardiovascular disease in patients with chronic kidney disease (CKD) not yet on dialysis is not known.

Methods: We performed a prospective study in patients with chronic kidney disease KDOQI stage 1-5 (Clinical trials protocol NCT00441623). Primary endpoint was time to first cardiovascular (CV) event, defined as myocardial infarction or ischemia, ventricular arythmia, ischemic cerebrovascular accident, symptomatic peripheral arterial disease, cardiovascular surgery or sudden cardiac death. Cox proportional hazard analysis was used.

Results: In a cohort of 499 CKD patients, after a mean follow up of 33 months, at least one cardiovascular event occurred in 62 patients. Higher baseline concentrations of free p- cresol were gradually and directly associated with CV events (univariate hazard ratio 1.79, P < 0.0001). Free p-cresol serum concentrations were inversely associated with eGFR (Spearman rank r = -0.70, P < 0.0001). In multivariate analysis, p-cresol remained a predictor of CV events, independent of markers of kidney function (HR 1.49, P = 0.01) and independent of other cardiovascular risk markers (HR 1.41, P = 0.01).

Conclusion: Free serum p-cresol concentrations are directly and gradually associated with cardiovascular disease in CKD and are a predictor of time to first CV events beyond other markers of kidney function. Together with previous observations of an independent association between p-cresol and cardiovascular disease in HD patients, these findings further substantiate the hypothesis that p-cresol directly contributes to the increased cardiovascular burden of patients with renal failure. From this, the development of strategies to eliminate these uremic toxins from the circulation would be expected to improve cardiovascular outcome of patients with chronic kidney disease.

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