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.