High protein-induced glomerular hypertrophy is vascular endothelial growth factor-dependent

Background. Various growth factors and cytokines have been implicated in different forms of kidney enlargement such as renal growth following induction of diabetes, unilateral nephrectomy, and exposure to high protein diet. Vascular endothelial growth factor (VEGF) is essential for normal renal development and plays a role in diabetes-associated renal and glomerular enlargement. Methods. To elucidate a possible role for VEGF in high protein-induced renal/glomerular enlargement, we examined the effect of a neutralizing VEGF-antibody (VEGF-ab) on kidney weight and glomerular volume in mice fed a high protein diet for up to seven days. Results. At day 2 and day 7 of the experimental period, high protein diet induced a significant increase in the mean glomerular volume. This high protein-induced glomerular hypertrophy was completely prevented by treatment with VEGF-ab. Kidney weight was increased significantly only at day 7, and was not influenced by VEGF-ab treatment. High protein diet and/or VEGF-ab treatment had no effect on body weight, food intake, and liver or heart weight. Conclusions. The administration of a neutralizing VEGF-ab in mice fed a high protein diet for one week completely abolished the glomerular hypertrophy seen in placebo-treated animals on the same diet, without affecting kidney and body weight. These results demonstrate, to our knowledge for the first time, that high protein-induced glomerular hypertrophy is VEGF-dependent.