Persistent kidney dysfunction in swine renal artery stenosis correlates with outer cortical microvascular remodeling

Abstract

Percutaneous transluminal renal stenting (PTRS) does not consistently improve renal function in patients with atherosclerotic renovascular disease, but the mechanisms underlying irreversible kidney injury have not been fully elucidated. We hypothesized that renal dysfunction after PTRS is linked to ongoing renal microvascular (MV) remodeling. Pigs were studied after 10 wk of atherosclerosis and renal artery stenosis (ARAS), ARAS treated with PTRS 4 wk earlier, and normal controls ( n = 10 each). Renal blood flow (RBF) and glomerular filtration rate (GFR) were studied using multidetector computer tomography. Renal microvascular architecture (micro-CT), angiogenic activity, oxidative stress, and fibrosis were evaluated ex vivo. Four weeks after PTRS, blood pressure was normalized. However, GFR and RBF remained similarly decreased in untreated ARAS and ARAS+PTRS ( P < 0.05 vs. normal). MV rarefaction was unaltered after revascularization, and the spatial density of outer cortical microvessels correlated with residual GFR. Interstitial fibrosis and altered expression of proangiogenic and profibrotic factors persisted after PTRS. Tubulointerstitial injury in ARAS persisted 4 wk after mechanically successful PTRS, and vessel loss correlated with residual renal dysfunction. MV loss and fibrosis in swine ARAS might account for persistent renal dysfunction after PTRS and underscore the need to assess renal parenchymal disease before revascularization.