Mechanism of kidney injury caused by bevacizumab in rats

Int J Clin Exp Pathol. 2014 Dec 1;7(12):8675-83. eCollection 2014.

Abstract

Objective: We investigate kidney injury caused by high dose bevacizumab to uncover the possible mechanisms involving in this process.

Methods: Forty rats were divided into four groups: cisplation group (treated with 1 mg/kg cisplation), Bev-high group (treated with 5 mg/kg bevacizumab); Bev-low group (treated with 2.5 mg/kg bevacizumab) and control group (treated with saline). The urine microalbumin, serum cystatin C, blood urea nitrogen and serum creatinine were detected in the four group rats, respectively. The immunoglobulin of IgG, IgA and IgM and protein of VEGF (vascular endothelial growth factor) and nephrin were detected by immunohistochemical methods.

Results: All the levels of microalbumin, cystatin C, serum creatinine and blood urea nitrogen in Bev-high group were significantly higher than those in normal control group (P < 0.05). The cystatin C was much more increased in kidney Bev-high group than cisplatin and Bev-low groups (P < 0.05). The light microscope showed a normal glomerular morphology in the four groups, while the electronic microscopy showed the podocytes were extensively fused in cisplatin group and Bev-high group. The two groups were found IgG and IgM deposition as well. The VEGF in kidney amples were down regulated in high dose bevacizumab group, whereas the nephrin and IgA showed no significant expression changes at all.

Conclusion: Bevacizumab increases the risk of injury in glomerular filtration barrier in a dose dependent model. The injury may not only associate with the rising level of proteinuria but also with podocyte-dependent membrane structures.

Keywords: Kidney injury; bevacizumab; glomerular filtration; immunoglobulin deposition; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / pathology
  • Angiogenesis Inhibitors / toxicity*
  • Animals
  • Antibodies, Monoclonal, Humanized / toxicity*
  • Antineoplastic Agents / toxicity
  • Bevacizumab
  • Cisplatin / toxicity
  • Immunohistochemistry
  • Kidney / drug effects
  • Kidney / ultrastructure
  • Kidney Function Tests
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Rats

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Bevacizumab
  • Cisplatin