Indoxyl Sulfate, a Tubular Toxin, Contributes to the Development of Chronic Kidney Disease

Tong Hong Cheng, Ming Chieh Ma, Min Tser Liao, Cai Mei Zheng, Kuo Cheng Lu, Chun Hou Liao, Yi Chou Hou, Wen Chih Liu, Chien Lin Lu

Research output: Contribution to journalReview articlepeer-review

5 Citations (Scopus)

Abstract

Indoxyl sulfate (IS), a uremic toxin, causes chronic kidney disease (CKD) progression via its tubulotoxicity. After cellular uptake, IS directly induces apoptotic and necrotic cell death of tubular cells. Additionally, IS increases oxidative stress and decreases antioxidant capacity, which are associated with tubulointerstitial injury. Injured tubular cells are a major source of transforming growth factor-β1 (TGF-β1), which induces myofibroblast transition from residual renal cells in damaged kidney, recruits inflammatory cells and thereby promotes extracellular matrix deposition in renal fibrosis. Moreover, IS upregulates signal transducers and activators of transcription 3 phosphorylation, followed by increases in TGF-β1, monocyte chemotactic protein-1 and α-smooth muscle actin production, which participate in interstitial inflammation, renal fibrosis and, consequently, CKD progression. Clinically, higher serum IS levels are independently associated with renal function decline and predict all-cause mortality in CKD. The poor removal of serum IS in conventional hemodialysis is also significantly associated with all-cause mortality and heart failure incidence in end-stage renal disease patients. Scavenging the IS precursor by AST-120 can markedly reduce tubular IS staining that attenuates renal tubular injury, ameliorates IS-induced oxidative stress and rescues antioxidant glutathione activity in tubular epithelial cells, thereby providing a protective role against tubular injury and ultimately retarding renal function decline.

Original languageEnglish
JournalToxins
Volume12
Issue number11
DOIs
Publication statusPublished - Oct 29 2020

Keywords

  • chronic kidney disease
  • indoxyl sulfate
  • oxidative stress
  • renal fibrosis
  • tubular injury

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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