Clinical trial NCT00433342: The Effect of Antimicrobial Therapy on the Serum Level of P-cresol in Peritoneal Dialysis Patients
Official title: Study on the Effect of Flucloxacillin on the Serum Level of P-cresol in Peritoneal Dialysis Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Kidney Disease
Keywords: Antibiotic
p-cresol
peritoneal dialysis
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2007-02-09
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: An important subgroup of protein-bound toxins are generated as a result of protein fermentation in the colon. P-cresol is a fermentation metabolite of tyrosine. In renal failure, the colonic generation rate of p-cresol is markedly elevated. After absorption, the majority of p-cresol is conjugated to form p-cresyl sulphate. There is clear evidence, both in vitro and in vivo, that accumulation of conjugated fermentation metabolites is correlated with clinical important endpoints. Free p-cresol is an independent predictor for mortality in hemodialysis patients.

Moreover, in renal failure patients, neither hemodialysis nor peritoneal dialysis is capable of normalising the clearly elevated serum concentrations of p-cresyl sulphate. Removal is at least partially diminished by the important protein binding of p-cresol. Besides adaptation of renal replacement therapies to improve removal of protein bound solutes, another approach is to lower the generation of uremic toxins.

The mechanisms underlying colonic carbohydrate and protein fermentation, responsible for the generation of p-cresol, are only partially understood. On the one hand, the ratio of fermentable carbohydrates to proteins has been shown to be an important determinant of protein fermentation. On the other hand, changes in the colonic bacterial flora influence the generation of p-cresol in dogs and in healthy human individuals.

The effect of antibiotic therapy on bacterial protein fermentation and thus on the generation of p-cresol is not known. A reanalysis of data abstracted from a recent longitudinal study in peritoneal dialysis (PD) patients suggests that antibiotic therapy may lower p-cresol levels substantially. The current study aims at confirming these data in a prospective manner.


Eligibility criteria: Inclusion Criteria:

* Age \> 18
* Exit site infection, requiring antibiotic treatment
* Maintenance therapy with peritoneal dialysis

Exclusion Criteria:

* Signs of peritonitis

Primary outcomes:
measure: p-cresol reduction rate
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
state: Vlaams-Brabant
Study officials:
affiliation: UZ Leuven
name: Björn Meijers, MD
role: STUDY_CHAIR
affiliation: UZ Leuven
name: Pieter Evenepoel, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Bammens B, Evenepoel P, Keuleers H, Verbeke K, Vanrenterghem Y. Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients. Kidney Int. 2006 Mar;69(6):1081-7. doi: 10.1038/sj.ki.5000115.