Indoxyl Sulfate and Atherosclerotic Risk Factors in Hemodialysis Patients

Indoxyl sulfate is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). Serum levels of indoxyl sulfate are increased in dialysis patients. It was reported that indoxyl sulfate plays a role in endothelial dysfunction in uremic patients, and stimulates proliferation of rat vascular smooth muscle cells (VSMC). We examined associations between indoxyl sulfate and several markers related to atherosclerosis.The association between indoxyl sulfate and atherosclerotic risk factors was studied in 224 hemodialysis (HD) patients (123 male, 101 female). Serum levels of indoxyl sulfate were measured by using high-performance liquid chromatography (HPLC).There were significant differences in serum levels of creatinine, calcium x phosphate and pentosidine between high- and low-indoxyl sulfate level groups. Indoxyl sulfate showed significant positive correlations with pentosidine, creatinine, and protein catabolic rate, and a significant negative correlation with high-density lipoprotein (HDL) cholesterol. Further, pentosidine, creatinine, and HDL-cholesterol were independently associated with indoxyl sulfate by multiple linear regression analysis.In addition to creatinine, pentosidine and HDL-cholesterol, the risk factors of atherosclerosis, were associated with indoxyl sulfate in HD patients. Indoxyl sulfate may be involved in the pathogenesis of atherosclerosis.