AST-120 Ameliorates Epithelial-to-Mesenchymal Transition and Interstitial Fibrosis in the Kidneys of Chronic Kidney Disease Rats

Objective: Indoxyl sulfate (IS), a uremic toxin, is a risk factor for progression of chronic kidney disease (CKD). AST-120 reduces serum IS and delays the progression of CKD. This study aimed to examine whether AST-120 inhibits epithelial-to-mesenchymal transition (EMT) in the kidneys of CKD rats. Methods: CKD rats were produced by 5/6 nephrectomy and were divided into 2 groups: (1) CKD rats and (2) AST-120-treated CKD rats at a dosage of 4 g/kg body weight/day. After 10 weeks, their kidneys were excised for histological and immunohistochemical analysis. EMT was evaluated by immunohistochemistry of zonula occludens (ZO-1), an epithelial marker, and alpha-smooth muscle actin (alpha-SMA), a mesenchymal marker. Interstitial fibrosis was evaluated by Masson's trichrome staining. Results: CKD rats showed reduced expression of ZO-1 and enhanced expression of a-SMA as compared with normal rats. Administration of AST-120 to CKD rats increased expression of ZO-1 and decreased expression of a-SMA as compared with CKD rats. Further, CKD rats showed enhanced extent of interstitial fibrosis as compared with normal rats, and administration of AST-120 to CKD rats ameliorated interstitial fibrosis. CKD rats showed increased serum level of IS as compared with normal rats, whereas administration of AST-120 to CKD rats decreased both serum and urine levels of IS. Conclusion: We conclude that AST-120 ameliorated EMT and interstitial fibrosis in the kidneys of CKD rats, probably by alleviating IS overload on the kidneys. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved.