Impaired Angiogenesis in the Remnant Kidney Model: II. Vascular Endothelial Growth Factor Administration Reduces Renal Fibrosis and Stabilizes Renal Function

Abstract

Abstract. Impaired angiogenesis and decreased vascular endothelial growth factor (VEGF) expression were recently documented in the remnant kidney (RK) model of progressive renal failure. VEGF (50 μg/kg, twice daily) was administered to RK rats between weeks 4 and 8 after surgery, and rats were euthanized at week 8 for histologic study. During the administration of VEGF (n= 7) or vehicle (n= 6), systemic BP was comparable in the two groups. VEGF treatment resulted in improved renal function and lower mortality rates, compared with the vehicle-treated group. Renal histologic analyses confirmed a 3.5-fold increase in glomerular endothelial cell proliferation (0.14 ± 0.03versus0.04 ± 0.02 proliferating endothelial cells/glomerulus, VEGFversusvehicle,P< 0.05), a twofold increase in peritubular capillary endothelial cell proliferation (1.60 ± 0.30versus0.78 ± 0.17 cells/mm2, VEGFversusvehicle,P< 0.01), a threefold decrease in peritubular capillary rarefaction (P< 0.01), and a twofold increase in endothelial nitrix oxide synthase expression (P< 0.05) in the VEGF-treated group; an eightfold increase in urinary nitrate/nitrite levels (P< 0.05) was also noted. Although the difference in glomerulosclerosis scores did not reach statistical significance (0.67 ± 0.42versus1.22 ± 0.63, VEGFversusvehicle; range, 0 to 4;P= NS), VEGF-treated rats exhibited less interstitial collagen type III deposition (9.32 ± 3.26versus17.45 ± 7.50%, VEGFversusvehicle,P< 0.01) and reduced tubular epithelial cell injury, as manifested by osteopontin expression (5.57 ± 1.60versus9.58 ± 3.45%, VEGFversusvehicle,P< 0.01). In conclusion, VEGF treatment reduces fibrosis and stabilizes renal function in the RK model. The use of angiogenic factors may represent a new approach to the treatment of kidney disease.