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Colonic microbial metabolism contributes substantially to uraemic retention solutes accumulating in chronic kidney disease (CKD) and various microbial–human co-metabolites relate to adverse outcomes. The influence of renal transplantation on these solutes is largely unexplored.We prospectively followed 51 renal transplant recipients at the time of transplantation, Day 7 and Months 3 and 12 post-transplantation. Serum levels of p-cresyl sulphate (PCS), p-cresyl glucuronide (PCG), indoxyl sulphate (IS), trimethylamine N-oxide (TMAO) and phenylacetylglutamine (PAG) were determined with liquid chromatography–tandem mass spectrometry. At each time point, transplant recipients were compared with CKD control patients matched for age, gender, diabetes mellitus and renal function. Determinants of serum levels were also compared between an unrelated cohort of 65 transplant recipients at Month 3 post-transplantation and CKD patients with 24-h urinary collection.Serum levels of the tested microbial–human co-metabolites significantly decreased following renal transplantation (P < 0.001). At each time point post-transplantation, serum levels of PCS, PCG, PAG and, to a lesser extent, IS, but not TMAO, were significantly lower in transplant recipients when compared with CKD control patients. Further analysis demonstrated significantly lower 24-h urinary excretion of these solutes in transplant recipients (P < 0.001). Also, renal clearances of PCG, IS, TMAO and PAG were significantly lower in transplant recipients without differences in estimated glomerular filtration rate.Colonic microbiota-derived uraemic retention solutes substantially decrease following renal transplantation. The 24-h urinary excretion of these microbial–human co-metabolites is lower when compared with CKD patients, suggesting an independent influence of transplantation on intestinal uptake, a composite of colonic microbial metabolism and intestinal absorption. Renal solute handling may differ between transplant recipients and CKD patients.