Ning Zhao1, Qunhong Xu1, Ming Wang1, Xiao Fei1, Yuelong Pan2, Xueqing Chen2, Shenglin Ma3. 1. Department of Nephrology, Hangzhou First People's Hospital Hangzhou 310006, Zhejiang Province, China. 2. Department of Oncology, Hangzhou Cancer Hospital Hangzhou 310006, Zhejiang Province, China. 3. Hangzhou First People's Hospital Hangzhou 310006, Zhejiang Province, China.
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.
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 ureanitrogen 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 ureanitrogen 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.
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