Preventive effects of an oval sorbent on nephropathy in rats

Circulating uremic substances are thought to be involved in the progression of chronic renal failure (CRF). An oral adsorbent AST-120 (Kremezin) is ef fective in removing circulating uremic toxins from the gastrointestinal tra ct, and retards the progression of CRF, AST-120 is widely used as an approv ed drug in Japan for the treatment of undialyzed uremic patients to delay t he progression of CRF. AST-120 attenuates the progression of glomerular scl erosis and interstitial fibrosis in a variety of experimental rat models of CRF. However, the mechanism by which AST-120 delays the progression of CRF had not been clear. We have demonstrated that indoxyl sulfate, a dietary p rotein metabolite, is a circulating uremic toxin stimulating glomerular scl erosis and interstitial fibrosis, and that AST-120 decreases the serum and urine levels of indoxyl sulfate by adsorbing its precursor, indole, in the intestine. The administration of indoxyl sulfate to uremic rats stimulated the expression of transforming growth factor (TGF)-beta 1, tissue inhibitor of metalloproteinase (TIMP)-1 and pro-alpha 1(l)collagen in the kidneys. F urther, the administration of AST-120 to uremic rats reduced the extent of glomerular sclerosis and interstitial fibrosis as well as the renal express ion of TGF-beta 1 and TIMP-1, by reducing the serum and urine levels of ind oxyl sulfate. We propose the protein metabolite hypothesis that endogenous protein metabolites such as indoxyl sulfate play an important role in the p rogression of CRF, and that AST-120 is effective in retarding the progressi on of CRF by removing these protein metabolites through intestinal absorpti on. Copyright (C) 2000 S. Karger AG, Basel.