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

NCT ID: NCT00441623

Last Updated: 2016-05-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 499 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2015-12-31

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.

Conditions

Chronic Kidney Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

observational

effect of protein-bound uremic retention solutes

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• age below 18
• Kidney transplant recipient

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Björn Meijers

Prof

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Björn KI Meijers, MD

Role: PRINCIPAL_INVESTIGATOR

Universitaire Ziekenhuizen KU Leuven

Pieter Evenepoel, MD, PhD

Role: STUDY_DIRECTOR

Universitaire Ziekenhuizen KU Leuven

Locations

Universitaire Ziekenhuizen Leuven

Leuven, Vlaams-Brabant, Belgium

Countries

Belgium

References

Evenepoel P, Claes K, Viaene L, Bammens B, Meijers B, Naesens M, Sprangers B, Kuypers D. Decreased Circulating Sclerostin Levels in Renal Transplant Recipients With Persistent Hyperparathyroidism. Transplantation. 2016 Oct;100(10):2188-93. doi: 10.1097/TP.0000000000001311.

Reference Type: DERIVED

PMID: 27379556 (View on PubMed)

Evenepoel P, Meijers B, Viaene L, Bammens B, Claes K, Kuypers D, Vanderschueren D, Vanrenterghem Y. Fibroblast growth factor-23 in early chronic kidney disease: additional support in favor of a phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism. Clin J Am Soc Nephrol. 2010 Jul;5(7):1268-76. doi: 10.2215/CJN.08241109. Epub 2010 May 6.

Reference Type: DERIVED

PMID: 20448073 (View on PubMed)

Meijers BK, Claes K, Bammens B, de Loor H, Viaene L, Verbeke K, Kuypers D, Vanrenterghem Y, Evenepoel P. p-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clin J Am Soc Nephrol. 2010 Jul;5(7):1182-9. doi: 10.2215/CJN.07971109. Epub 2010 Apr 29.

Reference Type: DERIVED

PMID: 20430946 (View on PubMed)

Other Identifiers

PCS001

Identifier Type: -

Identifier Source: org_study_id