Indoxyl sulfate and atherosclerotic risk factors in hemodialysis patients

Am J Nephrol. 2007;27(1):30-5. doi: 10.1159/000098542. Epub 2007 Jan 11.


Background: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Atherosclerosis / blood*
  • Atherosclerosis / epidemiology
  • Atherosclerosis / etiology
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cholesterol, HDL / blood
  • Chromatography, High Pressure Liquid
  • Creatinine / blood
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Glycation End Products, Advanced / blood
  • Humans
  • Incidence
  • Indican / blood*
  • Lysine / analogs & derivatives
  • Lysine / blood
  • Male
  • Middle Aged
  • Nephelometry and Turbidimetry
  • Renal Dialysis*
  • Uremia / blood
  • Uremia / complications
  • Uremia / therapy*


  • Biomarkers
  • Cholesterol, HDL
  • Glycation End Products, Advanced
  • C-Reactive Protein
  • Arginine
  • Creatinine
  • pentosidine
  • Lysine
  • Indican