Acarbose treatment lowers generation and serum concentrations of the protein-bound solute p-cresol: A pilot study

Abstract

Several protein-bound uremic retention solutes (including p-cresol) originate from colonic bacterial fermentation of protein. Higher colonic availability of carbohydrates drives this process towards lower production of toxic metabolites. Small intestinal alpha-glucosidase inhibitors like Acarbose (Glucobay) enhance the amount of undigested carbohydrates reaching the colon. We studied the effect of Acarbose on generation and serum concentrations of p-cresol. Nine healthy volunteers (age 25 (22-36) years) with a creatinine clearance of 89.6 ml/min/1.73 m(2) (85.5-116.4) were treated with Acarbose for 3 weeks. Dose was gradually increased to reach 300 mg/day after 1 week. Blood sampling, 24-h urine and stool collections on 3 consecutive days were performed before and during the last days of the treatment period. p-Cresol generation was estimated from mean 24-h urinary elimination. Gastrointestinal side effects, if present, were mild to moderate. Serum concentrations of p-cresol declined significantly after Acarbose treatment (before: 1.14 mg/l (0.93-3.03); after: 1.11 mg/l (0.31-1.82); P=0.047). Urinary excretion of p-cresol, reflecting its colonic generation rate, was significantly lower after treatment (before: 29.93 mg/day (6.79-75.19); after: 10.54 mg/day (1.08-30.85); P=0.031). The fecal excretion of nitrogen increased after treatment (before: 1.04 g/day (0.47-2.29); after: 1.99 g/day (0.76-3.08); P=0.047). This pilot study suggests that Acarbose treatment lowers generation and serum concentrations of the protein-bound uremic solute p-cresol. Although further confirmation is warranted, the data may point to a novel treatment option for chronic kidney disease patients in view of the potential toxic effects of p-cresol and related substances.