Pathophysiological role of vascular endothelial growth factor in the remnant kidney

Background: Subtotal renal ablation is characterized by initial glomerular hypertrophy, followed by progressive development of glomerulosclerosis and interstitial fibrosis. Vascular endothelial growth factor (VEGF) is involved in glomerular hypertrophy and dysfunction in several pathophysiological conditions. On the other hand, progressive glomerulosclerosis and tubulo-interstitial fibrosis in the remnant kidney have been associated with loss of VEGF expression. Methods: To explore the pathophysiological role of VEGF in the development of glomerular hypertrophy and renal damage in the remnant kidney model, we examined the effect of a neutralizing VEGF antibody on glomerular volume and kidney function in rats after subtotal nephrectomy or sham operation. Erythropoietin was administered to exclude a confounding effect of anaemia. Results: Six weeks after subtotal nephrectomy, plasma urea and creatinine concentrations, urinary albumin excretion, and mean glomerular volume were elevated in the placebo-treated uraemic rats as compared with the sham-operated rats. Inhibition of VEGF partially prevented the glomerular hypertrophy and largely prevented the rise in urinary albumin excretion, but did not affect creatinine clearance in uraemic rats. Conclusions: VEGF is a mediator of glomerular hypertrophy after subtotal renal ablation. In view of glomerular hypertrophy as the initial deleterious event ultimately leading to progressive glomerulosclerosis, agents that block this glomerular growth could be useful in preventing scarring in progressive renal disease.