Chronic Kidney Disease Clinical Trial
Official title:
Study on the Effect of Flucloxacillin on the Serum Level of P-cresol in Peritoneal Dialysis Patients
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.
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