Abstract 294: Intra-renal Administration of Hepatocyte-Growth Factor Reversed Microvascular Functional Rarefaction and Decreased Remodeling in the Stenotic Kidney

Abstract

Background: We have shown that renal microvascular (MV) damage and loss contributes to the progression of renal injury in the stenotic kidney (StK). Hepatocyte growth factor (HGF) is a powerful angiogenic and anti-fibrotic cytokine that we have shown to be reduced in the StK. Thus, we hypothesize that intra-renal administration of HGF will protect the renal MV architecture and function in the StK. Methods: Renal artery stenosis (RAS) was induced in 10 pigs. Pigs were observed untreated for 6 weeks and then RBF and GFR quantified in vivo using multi-detector CT. Then, rh-HGF (RAS+HGF, 2 ug/kg, single injection, n=5) or placebo (n=5) was infused in the StK, observed for 4 additional weeks, and in vivo CT studies repeated. Pigs were then euthanized at 10 weeks, StK removed, renal MV architecture quantified using 3D micro-CT in situ , and renal angiogenic activity, MV remodeling, and fibrosis was determined ex vivo . Results: Intra-renal administration of HGF improved RBF and GFR at 10 weeks, accompanied by improved angiogenic signaling, decreased MV remodeling and fibrosis. However, renal MV density not altered by treatment with HGF. (Figure). Conclusion: Despite a similar MV density, an intra-renal administration of HGF improved renal hemodynamics, decreased MV dysfunction and remodeling, and attenuated fibrosis, suggesting a protective effect of rh-HGF in the StK. These results indicate that, in the stenotic kidney, HGF has the potential to improve renal function by protecting the renal microvasculature.