The Role of P-cresol and Related Protein Fermentation Metabolites in Chronic Kidney Disease Patients

Completed

• Conditions: Chronic Kidney Disease

• Registration Number: NCT00441623
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

Brief Summary

Study on the natural history of uremic retention solutes in patients with mild-to-moderate chronic kidney disease

Detailed Description

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 Timeline

• Study Start: 2005-10
• Study First Submitted: 2007-02-28
• Study First Submitted QC: 2007-02-28
• Study First Posted: 2007-03-01
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-12
• Last Update Posted: 2016-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 499

Inclusion Criteria

• Informed consent
• Chronic kidney disease, stage 1-4 kDOQI

Exclusion criteria

• age below 18
• Kidney transplant recipient

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Trial Locations

Locations (1)

Universitaire Ziekenhuizen Leuven; 🇧🇪 Leuven, Vlaams-Brabant, Belgium