Early atherosclerosis aggravates renal microvascular loss and fibrosis in swine renal artery stenosis

•Renal artery stenosis (RAS) and atherosclerotic RAS (ARAS) induce similar hypertension and stenotic-kidney dysfunction.•Swine ARAS magnifies loss of stenotic-kidney cortical microvessels.•Cortical hypoxia and fibrosis do not correlate with micro vascular loss in RAS.•In swine, ARAS determinants additional to RAS alone contribute to cortical injury.

Renal function in patients with atherosclerosis and renal artery stenosis (ARAS) deteriorates more frequently than in nonatherosclerotic RAS. We hypothesized that ARAS aggravates stenotic-kidney micro vascular loss compared to RAS. Domestic pigs were randomized to normal, RAS, and ARAS (RAS fed a high-cholesterol diet) groups (n = 7 each). Ten weeks later stenotic-kidney oxygenation, renal blood flow, and glomerular filtration rate (GFR) were evaluated in vivo, and micro vascular density by micro-computed tomography. Blood pressure in both RAS and ARAS was elevated; and stenotic-kidney renal blood flow and GFR similarly decreased. RAS decreased the density of small-size cortical microvessels (<200 μm), whereas ARAS extended the decrease to medium-sized microvessels (200–300 μm). Cortical hypoxia and interstitial fibrosis increased in both RAS and ARAS but correlated inversely with micro vascular density only in RAS. Atherosclerosis aggravates loss of stenotic-kidney microvessels, yet additional determinants likely contribute to cortical hypoxia and fibrosis in swine ARAS.