Abstract 430: Vascular Contrast Increases Permeability of Proximal Tubule Epithelium: A Possible Mechanism of Contrast-Induced Nephropathy
Objectives: Contrast Induced Nephropathy (CIN) is the third leading cause of hospital acquired renal failure and excludes numbers of patients from less invasive endovascular procedures. The mechanism of CIN is not fully understood. We investigated the hypotheses that CIN may result from direct toxicity or malfunction of kidney cells caused by contrast agent.
Methods: Human kidney 2 (HK-2) cells were treated with Phosphate-Buffered Saline (PBS) or Iodixanol, a contrast agent, representing control and experimental groups. TUNEL assay was used to evaluate apoptosis. Cell proliferation was measured by BrdU incorporation. Expression of Claudin-2, a tight junction protein, was assessed by qRT-PCR and western blot. Intercellular gaps were measured using phase contrast microscopy and quantified by Image J software.
Results: Iodixanol reduced tubule cell proliferation, but did not cause apoptosis. Phase contrast imaging of HK-2 cells demonstrated that intercellular gaps within the monolayer of cells were significantly increased by Iodixanol in a dose dependent manner. Western blot and qRT-PCR showed up-regulation of claudin-2 protein and mRNA expression. Both intercellular gap formation and up-regulation of claudin-2 expression are consistent with possible increase of permeability across proximal tubule epithelium, which is one of the known causes of renal failure. Conclusion: Our in vitro data do not support the hypothesis that direct kidney cell death from contrast agent is a major mechanism of CIN. However, increased permeability of proximal tubule epithelium caused by contrast may play an important role in CIN.
- © 2012 by American Heart Association, Inc.