Anti-VEGF antibody treatment accelerates polycystic kidney disease - PubMed (original) (raw)

. 2011 Oct;301(4):F773-83.

doi: 10.1152/ajprenal.00058.2011. Epub 2011 Jun 15.

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• PMID: 21677148
• DOI: 10.1152/ajprenal.00058.2011

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Anti-VEGF antibody treatment accelerates polycystic kidney disease

Shagun Raina et al. Am J Physiol Renal Physiol. 2011 Oct.

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Abstract

Polycystic kidney growth implies expansion of the vasculature, suggesting that vascular endothelial growth factor (VEGF)-dependent processes play a critical role and that VEGF is a putative therapeutic target. Whether an anti-VEGF antibody improves renal cystic disease has not been determined. We administrated 5 mg/kg B20.4.1, an anti-VEGF-A antibody, or vehicle intraperitoneally twice weekly to 4-wk-old male normal (+/+) and cystic (Cy/+) Han:SPRD rats for 6 wk. Renal function, urinary protein excretion, organ/body weight ratios, cyst volume, tubular epithelial cell (TEC) proliferation, renal VEGF, hypoxia-inducible factor (HIF)-1α and -2α expression, renal histology, and kidney hypoxia visualized by [(18)F]fluoromisonidazole positron emission tomography were assessed. The treated compared with untreated +/+ rats had lower TEC proliferation rates, whereas Cy/+ rats receiving B20.4.1 displayed an increased proximal TEC proliferation rate, causing enhanced cyst and kidney growth. The +/+ and Cy/+ rats receiving B20.4.1 had severe renal failure and extensive glomerular damage. Proteinuria, which was highest in anti-VEGF-treated Cy/+ and lowest in untreated normal littermates, was positively correlated with renal HIF-1α and negatively correlated with VEGF expression. The untreated Cy/+ vs. +/+ rats had higher overall [(18)F]fluoromisonidazole uptake. The +/+ rats receiving B20.4.1 vs. untreated had increased [(18)F]fluoromisonidazole uptake, whereas the uptake was unchanged among treated vs. untreated Cy/+ animals. In conclusion, B20.4.1 caused an exaggerated cystic response of the proximal tubules in cystic rats and severe kidney injury that was associated with low renal VEGF and high HIF-1α levels. Anti-VEGF drug therapy may therefore not be a treatment option for polycystic kidney disease.

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