An oral adsorbent ameliorates renal overload of indoxyl sulfate and progression of renal failure in diabetic rats

Otsuka Long-Evans Tokushima Fatty (OLETF) rats were established as a new mo del of non-insulin-dependent diabetes mellitus. An oral adsorbent, AST-120, is effective in removing such uremic toxins as indoxyl sulfate and delays the progression of chronic renal failure (CRF). This study was designed to determine the effects of AST-120 on the progression of CRF in uninephrectom ized OLETF (1/2NxOLETF) rats and the localization of indoxyl sulfate in the ir kidneys. Four weeks after unilateral nephrectomy, 14 OLETF rats were div ided into two groups; AST-120-administered and control 1/2NxOLETF rats. Lon g-Evans Tokushima Otsuka rats, which are genetically similar to the OLETF r ats but not diabetic, were also included. After the administration of AST-1 20 for 36 weeks, we examined the effects of AST-120 on renal functional and pathological changes in the three groups. The control 1/2NxOLETF rats show ed marked hyperglycemia, hyperlipidemia, renal failure, glomerular sclerosi s, and tubulointerstitial injury. The administration of AST-120 to the 1/2N xOLETF rats retarded the progression of renal dysfunction and fibrosis, as well as hyperlipidemia, and reduced serum and urinary levels of indoxyl sul fate. Immunohistochemistry showed that AST-120 markedly reduced the overloa d of indoxyl sulfate in tubular epithelial cells, especially dilated tubule s, of the 1/2NxOLETF rats. In conclusion, AST-120 delayed the progression o f renal failure and fibrosis in 1/2NxOLETF rats and decreased the overload of indoxyl sulfate on renal tubular cells. (C) 2001 by the National Kidney Foundation, Inc.