Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Transplantation, Urology & Nephrology, haemodialysis, indoxyl sulfate, intervention study, p-cresol, prebiotic, INDOXYL SULFATE, ALBUMIN-BINDING, UREMIC SOLUTES, PROTEIN, METABOLITES, EXPRESSION, CLEARANCE, MORTALITY, TRANSPORT, DIALYSIS, Administration, Oral, Aged, Cresols, Female, Humans, Indican, Inulin, Kidney Failure, Chronic, Male, Middle Aged, Oligosaccharides, Prebiotics, Renal Dialysis, Sulfuric Acid Esters, 1103 Clinical Sciences, 3202 Clinical sciences

Abstract:

Introduction. Protein-bound uraemic retention solutes, including p-cresyl sulfate and indoxyl sulfate, contribute substantially to the uraemic syndrome. These and several other uraemic retention solutes originate from intestinal bacterial protein fermentation. We investigated whether the prebiotic oligofructose-enriched inulin reduced serum concentration of p-cresyl sulfate and indoxyl sulfate, through interference with intestinal generation. METHODS: We performed a single centre, non-randomized, open-label phase I/II study in maintenance HD patients with a 4-week, escalating dose regimen of oligofructose-enriched inulin (ORAFTI(R)Synergy 1, Tienen, Belgium) (www.clinicaltrials.gov NCT00695513). Changes in p-cresyl sulfate and indoxyl sulfate serum concentrations as well as changes in p-cresyl sulfate and indoxyl sulfate generation rates were analysed. RESULTS: Compliance with therapy was excellent. p-Cresyl sulfate serum concentrations at 4 weeks were significantly reduced by 20% (intention to treat, P = 0.01; per protocol, P = 0.03). Also p-cresyl sulfate generation rates were reduced (P = 0.007). In contrast, neither indoxyl sulfate generation rates (P = 0.9) nor serum concentrations (P = 0.4) were significantly changed. CONCLUSION: The prebiotic oligofructose-inulin significantly reduced p-cresyl sulfate generation rates and serum concentrations in haemodialysis patients. Whether reduction of p-cresyl sulfate serum concentrations, an independent predictor of cardiovascular disease in HD patients, will result in improved cardiovascular outcomes remains to be proven.