title: Mechanism of kidney injury caused by bevacizumab in rats.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Nephrology, Hangzhou First People's Hospital Hangzhou 310006, Zhejiang Province, China.
authors: Ning
authors: N
authors: Zhao
authors: Department of Nephrology, Hangzhou First People's Hospital Hangzhou 310006, Zhejiang Province, China.
authors: Qunhong
authors: Q
authors: Xu
authors: Department of Nephrology, Hangzhou First People's Hospital Hangzhou 310006, Zhejiang Province, China.
authors: Ming
authors: M
authors: Wang
authors: Department of Nephrology, Hangzhou First People's Hospital Hangzhou 310006, Zhejiang Province, China.
authors: Xiao
authors: X
authors: Fei
authors: Department of Oncology, Hangzhou Cancer Hospital Hangzhou 310006, Zhejiang Province, China.
authors: Yuelong
authors: Y
authors: Pan
authors: Department of Oncology, Hangzhou Cancer Hospital Hangzhou 310006, Zhejiang Province, China.
authors: Xueqing
authors: X
authors: Chen
authors: Hangzhou First People's Hospital Hangzhou 310006, Zhejiang Province, China.
authors: Shenglin
authors: S
authors: Ma
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000633:toxicity*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity; D000068258:Bevacizumab; D002945:Cisplatin / Q000633:toxicity; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000648:ultrastructure; D007677:Kidney Function Tests; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D051381:Rats
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D002945:Cisplatin
keywords: Kidney injury; bevacizumab; glomerular filtration; immunoglobulin deposition; vascular endothelial growth factor