Intravascular radiocontrast iodixanol increases permeability of proximal tubule epithelium: a possible mechanism of contrast-induced nephropathy

Vasc Endovascular Surg. 2013 Nov;47(8):632-8. doi: 10.1177/1538574413503560. Epub 2013 Sep 4.

Abstract

Purpose: To investigate the effect of Iodixanol on kidney proximal tubular cell line human kidney 2 (HK-2).

Methods: The HK-2 cells were treated with Iodixanol. A Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis. Cell viability was measured by proliferation assay kit. Cell permeability changes were assessed by transwell assay and intercellular gaps measurement. Expression of claudin-2 was assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot.

Results: Iodixanol reduced tubule cell viability (P < .01) but did not cause apoptosis. The intercellular gap formation (P < .01) and transwell (P < .05) assays revealed that cell permeability significantly increased after Iodixanol treatment of monolayer cells. Western blot and qRT-PCR showed significant upregulation of claudin-2 protein (P < .05) and messenger RNA expression (P < .01).

Conclusions: Our in vitro data do not support the hypothesis that direct kidney cell death from Iodixanol is a major mechanism of contrast-induced nephropathy (CIN). However, increased permeability of proximal tubule epithelium caused by Iodixanol may play an important role in CIN.

Keywords: contrast-induced nephropathy; iodixanol; permeability; proximal tubule epithelium.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Claudins / genetics
  • Claudins / metabolism
  • Contrast Media / toxicity*
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Humans
  • Intercellular Junctions / drug effects*
  • Intercellular Junctions / metabolism
  • Intercellular Junctions / pathology
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology
  • Permeability
  • Triiodobenzoic Acids / toxicity*
  • Up-Regulation

Substances

  • CLDN2 protein, human
  • Claudins
  • Contrast Media
  • Triiodobenzoic Acids
  • iodixanol