The Effect of Antimicrobial Therapy on the Serum Level of P-cresol in Peritoneal Dialysis Patients

NCT ID: NCT00433342

Last Updated: 2020-04-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2020-04-30

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.

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

I

Flucloxacillin

Group Type: EXPERIMENTAL

Flucloxacillin

Intervention Type: DRUG

500 mg QD oral

II

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Flucloxacillin

500 mg QD oral

Intervention Type: DRUG

Other Intervention Names

Floxapen

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• Signs of peritonitis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Björn Meijers

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Björn Meijers, MD

Role: STUDY_CHAIR

UZ Leuven

Pieter Evenepoel, MD, PhD

Role: STUDY_DIRECTOR

UZ Leuven

Locations

Universitaire Ziekenhuizen Leuven

Leuven, Vlaams-Brabant, Belgium

Countries

Belgium

References

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.

Reference Type: BACKGROUND

PMID: 16421516 (View on PubMed)

Other Identifiers

ML3532

Identifier Type: -

Identifier Source: org_study_id