Chronic Kidney Disease Clinical Trial
Official title:
A Single Centre Observational Cohort Study on the Prognostic Relevance of P-cresol and Related Uremic Retention Solutes in the Development and/or Progression of Renal Failure and Cardiovascular Disease in Chronic Kidney Disease Patients
Study on the natural history of uremic retention solutes in patients with mild-to-moderate chronic kidney disease
Protein-bound uremic retention solutes are increasingly recognized to play a role in the
pathophysiology of the uremic syndrome. Numerous in vitro findings are indicative for their
implication in the biochemical and physiological changes of uremia. Several of these
protein-bound retention solutes originate from bacterial protein fermentation in the colon.
p-cresyl sulfate, a fermentation metabolite of the amino acid tyrosine, is considered a
prototype of this group of uremic solutes. The protein binding of this molecule was shown to
be about 90% in end-stage renal disease patients. Several data have suggested that p-cresol
plays a role in the immunodeficiency of uremia. Recently, a link between the molecule and
endothelial dysfunction has been demonstrated. Also other members of the class of
protein-bound solutes have been found to be associated with immune dysfunction, endothelial
cell dysfunction and, closely related to the latter, oxidative stress.
Free serum levels of p-cresol were shown to be greater in stage 5 chronic kidney disease
(CKD) patients treated with hemodialysis (HD) hospitalized for infectious disease.
Furthermore, a positive relationship was found between serum total p-cresol level and a
uremic symptom score in patients treated with peritoneal dialysis (PD), whereas a
correlation with small water-soluble solutes and the middle molecule β2-microglobulin was
absent. A recent prospective observational study in stage 5 CKD patients treated with
conventional HD (3 x 4 hours per week) indicated that the accumulation of p-cresol is a risk
factor for overall mortality.
Data on the serum concentrations of p-cresol in chronic kidney disease patients are lacking.
The investigators hypothesise that the serum concentration of p-cresol is an independent
predictor of progression to end stage renal disease and is an independent predictor for
cardiovascular disease.
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