Early and delayed effects of AST-120 on chronic cyclosporine nephropathy

Abstract

Background. Removal of uraemic toxins by AST-120 (Kremezin (R)) decreases the progression of chronic kidney disease by reducing oxidative stress. We performed this study to evaluate whether AST-120 has a similar effect on progression of cyclosporine (CsA)-induced renal injury. Methods. Two separate studies were performed in adult Sprague-Dawley rats. First, AST-120 was administered with CsA (15 mg/kg) for 4 weeks (early treatment). Second, AST-120 was administered to the rats for 3 weeks after treatment with CsA for 3 weeks (delayed treatment). Uraemic toxin and oxidative stress were evaluated with plasma indoxyl sulphate (IS) levels and urinary 8-OHdG excretion. The effects of AST-120 on CsA-induced renal injury were evaluated in terms of renal function, interstitial fibrosis, inflammation, and apoptotic cell death. Results. CsA treatment for 4 weeks showed 2-fold increase in plasma IS and urinary 8-OHdG levels compared with the VH group. Early treatment with AST-120 significantly decreased both parameters, and this was accompanied by improved renal function and decreased interstitial inflammation, fibrosis, and apoptotic cell death compared with those of rats that received CsA alone. Delayed treatment with AST-120 also decreased the plasma IS and urinary 8-OHdG levels, and reduced the progression of chronic CsA nephropathy. Furthermore, delayed AST-120 treatment decreased the epithelial-mesenchymal transition in chronic CsA nephropathy. Conclusions. Removal of uraemic toxins with AST-120 treatment is effective in decreasing the progression of CsA-induced renal injury by reducing oxidative stress.