1. ¹Department of Medicine, Division of Nephrology, University Hospital Gasthuisberg, Leuven, Belgium
2. ²Department of Medicine, Division of Nephrology, Virga Jesse Hospital, Hasselt, Belgium
3. ³Laboratory of Digestion and Absorption, University Hospital Gasthuisberg, Leuven, Belgium

Correspondence: P Evenepoel, Department of Medicine, Division of Nephrology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. E-mail: Pieter.Evenepoel@uz.kuleuven.ac.be

Received 18 April 2005; Revised 2 September 2005; Accepted 5 October 2005; Published online 18 January 2006.

Abstract

Based on in vitro data, protein-bound uremic retention solutes have increasingly been recognized to play a pathophysiological role in the uremic syndrome. p-Cresol, a representative of this group of molecules, has been shown to be implicated in uremic immunodeficiency and endothelial dysfunction, potentially linking its serum levels to mortality. Thus far, however, no clinical information on this issue is available. To determine the relationship between p-cresol and all-cause mortality, 175 prevalent hemodialysis (HD) patients were enrolled in a prospective study. At baseline, serum levels of the water-soluble solutes urea, creatinine, and phosphate, the middle molecule ₂-microglobulin, total and free concentrations of the protein-bound solute p-cresol, and several risk factors for mortality were evaluated. During a median follow-up of 34 months, 60 patients died. Baseline comorbidity (Davies score) (hazard ratio (HR), 1.49; 95% confidence interval (95% CI), 1.19–1.86), impaired nutritional status (HR, 4.22; 95% CI, 2.15–8.29), time since initiation of dialysis (HR, 0.98; 95% CI, 0.97–1.00), and higher free concentrations of the protein-bound solute p-cresol (HR, 2.28; 95% CI, 1.12–4.64) were independently associated with mortality (multivariate Cox proportional hazards analysis). Our data suggest that free serum levels of p-cresol, a representative of the protein-bound uremic retention solutes, are associated with mortality in HD patients. These findings may encourage nephrologists to widen their field of interest beyond the scope of small water-soluble uremic solutes and middle molecules.