Reversal of advanced diabetic kidney disease in mice treated with a monoclonal anti-VEGFR1 antibody

INTRODUCTION: Diabetic kidney disease (DKD) continues to be the major cause of kidney failure, and its treatment is of key importance. Targeting VEGF-A has yielded conflicting results in DKD models. Here, we investigated the potential benefit of targeting VEGF-A or its receptors for the treatment of advanced mouse DKD. METHODS: Our studies tested the effects of neutralizing antibodies targeting VEGF-A, VEGFR2, and VEGFR1 on kidney function and histopathology, in 4 different mouse models of DKD and chronic kidney disease (CKD). RESULTS: mice and acutely increased the glomerular filtration rate in db/db mice. CONCLUSIONS: Our studies demonstrate that blocking VEGFR1 improved kidney function and microvascular structure in models of progressive CKD. VEGFR1 blockade provided a promising novel therapeutic approach to reverse DKD progression.