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 progression 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 chronic 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 creatinine (Scr)-time plot, and the serum and urine levels of indoxyl sulfate were evaluated. Administration of AST-120 significantly decreased the serum and urine levels of indoxyl sulfate, and tended to improve the slope of the 1/SCr-time plot in the CRF patients. Among the patients in whom urinary excretion of indoxyl sulfate was reduced by AST-120, the oral adsorbent significantly improved the slope of the 1/SCr-time plot. The change in the slope of the 1/SCr-time plot showed a significant negative correlation with the change in the urine level of indoxyl 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 protein metabolite, is involved in the progression of CRF, and that an oral adsorbent can delay progression at least partly by reducing the serum and urine levels of indoxyl sulfate.