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

Chronic Kidney Disease Clinical Trial

Official title:

Study on the Effect of Flucloxacillin on the Serum Level of P-cresol in Peritoneal Dialysis Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00433342
• Other study ID #: ML3532
• Status: Terminated
• Phase: Phase 1
• Start date: March 2006
• Est. completion date: April 2020

Study information

• Verified date: April 2020
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: April 2020
• Est. primary completion date: April 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18

• Exit site infection, requiring antibiotic treatment

• Maintenance therapy with peritoneal dialysis

Exclusion Criteria:

• Signs of peritonitis

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Flucloxacillin
500 mg QD oral

Locations

Country	Name	City	State
Belgium	Universitaire Ziekenhuizen Leuven	Leuven	Vlaams-Brabant

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven

Country where clinical trial is conducted

Belgium, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	p-cresol reduction rate		8 weeks