Gut-derived uremic toxin handling in vivo requires OAT-mediated tubular secretion in chronic kidney disease.

ABSTRACT: The role of the renal organic anion transporters OAT1 (also known as SLC22A6, originally identified as NKT) and OAT3 (also known as SLC22A8) in chronic kidney disease (CKD) remains poorly understood. This is particularly so from the viewpoint of residual proximal tubular secretion, a key adaptive mechanism to deal with protein-bound uremic toxins in CKD. Using the subtotal nephrectomy (STN) model, plasma metabolites accumulating in STN rats treated with and without the OAT inhibitor, probenecid, were identified. Comparisons with metabolomics data from Oat1-KO and Oat3-KO mice support the centrality of the OATs in residual tubular secretion of uremic solutes, such as indoxyl sulfate, kynurenate, and anthranilate. Overlapping our data with those of published metabolomics data regarding gut m

SUBMITTER: Bush KT 

PROVIDER: S-EPMC7205256 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature