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.

Cell-Based Therapies as an Adjunct to Revascularization in Experimental Atherosclerotic Reno Vascular Disease

“…While small clinical studies have reported significant improvement in blood pressure and renal function among PTRA-treated patients [4,5], large randomized clinical trials failed to determine an incremental value of PTRA, on a top of medical therapy, for the treatment of ARVD [6,7]. In agreement, we have previously shown in a swine model of ARVD that PTRA normalizes blood pressure levels, but fails to improve tubulointerstitial injury, microvascular rarefaction, and renal function in the stenotic kidney [8].…”

Determination of Single-Kidney Glomerular Filtration Rate in Human Subjects by Using CT

“…In addition, although the Bland-Altman analysis did not exhibit a consistent bias, lower GFR values might narrow the differences between two methods. Notably, restoring stenotic kidney blood flow after stent placement was not associated with (32). Our methods are limited by the use of central contrast material injection by using a catheter advanced after renal vein sampling.…”

Blood Flow, Oxygenation, and Oxidative Stress in the Post-stenotic Kidney

“…Partial reversal of these structural and functional changes in the cortical circulation, and increased basal RBF and GFR, is seen after percutaneous transluminal renal artery stenting, to remove the stenosis, at least in a porcine model of RVD uncomplicated by hypercholesterolemia [ 67 ]. However, this treatment is much less effective when RVD is complicated by atherosclerosis [ 65 ]. Thus, renal artery stenosis, particularly when accompanied by hypercholesterolemia, appears to set in train a cascade of events, associated with oxidative stress, fi brosis, infl ammation, apoptosis, vascular remodeling and endothelial dysfunction, which are at best only partially reversible.…”