Oral adsorbent AST-120 ameliorates interstitial fibrosis and transforming growth factor-beta(1) expression in spontaneously diabetic (OLETF) rats

Diabetic nephropathy is a common cause of end-stage renal disease. The admi nistration of an oral adsorbent, AST-120, prevents the progression of chron ic renal failure in uremic rats and undialyzed uremic patients. This study was designed to determine if AST-120 slows the progression of diabetic neph ropathy using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of no ninsulin-dependent diabetic mellitus. At 21 weeks of age the OLETF rats wer e divided into 2 groups: AST-120-administered OLETF rats (n = 7), and contr ol OLETF rats (n = 7). LETO rats, which are genetically similar to the OLET F rats but not diabetic, were also included. After the oral administration of AST-120 for 65 weeks, renal function and pathological changes were inves tigated in the 3 groups. The administration of AST-120 to the OLETF rats at tenuated the progression of glomerular sclerosis, interstitial fibrosis, tu bular injury as well as renal dysfunction, and reduced the serum and urinar y levels of indoxyl sulfate. Furthermore, AST-120 administration reduced th e interstitial expression of transforming growth factor (TGF)-beta(1) and t issue inhibitor of metalloproteinase (TIMP)-1, as well as interstitial infi ltration of macrophages. The TGF-beta(1)-stained interstitial area showed p ositive correlations with the interstitial fibrosis area, the number of TIM P-1-positive cells, and the number of macrophages, and showed a negative co rrelation with creatinine clearance. In conclusion, AST-120 reduced the int erstitial expression of TGF-beta(1) and TIMP-1, and the interstitial infilt ration of macrophages, and ameliorates the progression of diabetic nephropa thy in OLETF rats. Copyright (C) 2000 S. Karger AG, Basel.