Clinical trial NCT00441623: The Role of P-cresol and Related Protein Fermentation Metabolites in Chronic Kidney Disease Patients
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 type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Kidney Disease
Keywords: chronic kidney disease
cardiovascular disease
risk stratification
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2007-03-01
Enrollment: 499
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: chronic kidney disease patients KDOQI stage 1-5 not yet on dialysis

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion criteria

* age below 18
* Kidney transplant recipient

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
state: Vlaams-Brabant
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Björn KI Meijers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Pieter Evenepoel, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.