PROGRESSION OF GLOMERULAR SCLEROSIS IN EXPERIMENTAL UREMIC RATS BY ADMINISTRATION OF INDOLE, A PRECURSOR OF INDOXYL SULFATE

In uremia there is a marked elevation of serum levels of indoxyl sulfa te due to its decreased renal clearance. Indoxyl sulfate is synthesize d in the liver from indole which is produced by bacteria in the intest ines. To determine the role of indoxyl sulfate in the progression of c hronic renal failure, we administered indole, the precursor of indoxyl sulfate, to subtotally nephrectomized uremic rats. The oral administr ation of indole increased the serum levels of creatinine and blood ure a nitrogen and decreased creatinine, inulin, and p-aminohippuric acid clearances. The glomerular sclerosis index in the indole-treated rats was higher than in the control uremic rats. After oral administration, indole could not be detected in the urine, but large amounts of its m etabolite, indoxyl sulfate. Thus, indole administration stimulated glo merular sclerosis in a uremic model through the production of indoxyl sulfate.