Renal Microvascular Disease and the Responses to Renal Revascularization

Abstract

Renal angioplasty and stenting (PTRA) is the most frequent therapeutic approach for renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesize that preserving the renal microcirculation in the stenotic kidney will improve the responses to PTRA.RAS was induced in 12 pigs. In 6 pigs, VEGF‐165 was single‐infused intra‐renally (RAS+VEGF, 0.05 ug/kg). Additional animals were used as normal controls (n=6), and all were followed for 10 weeks. Single‐kidney function was assessed in vivo using ultra‐fast CT after 6 weeks of RAS. Then, RAS and RAS+VEGF underwent PTRA, VEGF repeated, and CT studies performed 4 weeks post‐PTRA. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex‐vivo using 3D micro‐CT, and renal fibrosis quantified.Degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF.PTRA largely resolved RAS. Improvements in blood pressure and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 29% increase in MV density and decreased fibrosis.Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV rarefaction plays a role in determining the responses to PTRA. This study indicates that the damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage.Support: AHA‐SDG‐0830100N