Iindoxyl sulfate, a tryptophan metabolite, induces nephro-vascular toxicity

Abstract

Indoxyl sulfate, a uremic toxin, is accumulated in the serum of chronic kidney disease (CKD) patients. A part of the dietary protein-derived tryptophan is metabolized by intestinal bacteria into indole, which is metabolized to indoxyl sulfate in the liver. Indoxyl sulfate stimulates progression of CKD by increasing expression of fibrogenic genes such as transforming growth factor (TGF)-β1. AST-120 delays the progression of CKD by adsorbing indole in the intestines, and consequently reducing serum indoxyl sulfate. Indoxyl sulfate exhibits cellular toxicity in renal tubular cells, glomerular mesangial cells, vascular smooth muscle cells, vascular endothelial cells, and cardiac myocytes by inducing reactive oxygen species. Indoxyl sulfate induces cell senescence in renal tubular cells. Indoxyl sulfate stimulates aortic calcification and senescence in hypertensive rats. Thus, indoxyl sulfate is involved in the progression of CKD and cardiovascular disease (CVD).