THE PROTEIN METABOLITE HYPOTHESIS, A MODEL FOR THE PROGRESSION OF RENAL-FAILURE - AN ORAL ADSORBENT LOWERS INDOXYL SULFATE LEVELS IN UNDIALYZED UREMIC PATIENTS

We have recently demonstrated that indoxyl sulfate promotes the progre ssion of glomerular sclerosis in uremic rats. In the present study, we determined whether an oral adsorbent (AST-120) could reduce the serum and urine levels of indoxyl sulfate and suppress the progression of c hronic renal failure (CRF) in undialyzed uremic patients. Twenty-five undialyzed uremic patients were given AST-120 at a dose of 6 g/day for 6 months, while 10 undialyzed uremic patients were not given AST-120. The effects of the oral adsorbent on the slope of the 1/serum creatin ine (S-Cr)-time plot, and the serum and urine levels of indoxyl sulfat e were evaluated. Administration of AST-120 significantly decreased th e serum and urine levels of indoxyl sulfate, and tended to improve the slope of the 1.2(Cr)-time plot in the CRF patients. Among the patient s in whom urinary excretion of indoxyl sulfate was reduced by AST-120, the oral adsorbent significantly improved the slope of the 1/S-Cr-tim e plot. The change in the slope of the 1/S-Cr,-time plot showed a sign ificant negative correlation with the change in the urine level of ind oxyl sulfate. Thus, patients who showed a greater decrease of urinary indoxyl sulfate also showed more marked suppression of the progression of CRF. These results support the notion that indoxyl sulfate, a prot ein metabolite, is involved in the progression of CRF, and that an ora l adsorbent can delay progression at least partly by reducing the seru m and urine levels of indoxyl sulfate.