The Role of P-cresol and Related Protein Fermentation Metabolites in Chronic Kidney Disease Patients
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.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|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|
Serum, plasma Urine (if provided by patient)
|Study Start Date:||October 2005|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00441623
|Universitaire Ziekenhuizen Leuven|
|Leuven, Vlaams-Brabant, Belgium, 3000|
|Principal Investigator:||Björn KI Meijers, MD||Universitaire Ziekenhuizen Leuven|
|Study Director:||Pieter Evenepoel, MD, PhD||Universitaire Ziekenhuizen Leuven|