Early atherosclerosis aggravates the effect of renal artery stenosis on the swine kidney

Abstract

Atherosclerotic renal artery stenosis (ARAS) is increasingly identified in patients with end-stage renal disease. Renal function in ARAS patients deteriorates more frequently than in nonatherosclerotic renal artery stenosis (RAS). This study was designed to test the hypothesis that atherosclerosis modifies the relationship between single-kidney hemodynamics and function and the severity of stenosis. The degree of unilateral RAS in domestic pigs (4 normal, 26 RAS, and 22 ARAS) was correlated with renal function and hemodynamics evaluated by 64-slice multidetector computerized tomography before and after endothelium-dependent challenge with ACh. The degree of stenosis and increase in mean arterial pressure were similar in RAS and ARAS. Stenotic single-kidney volume, blood flow, glomerular filtration rate, and cortical perfusion were lower than normal in both RAS and ARAS, but only in RAS correlated inversely with increasing degree of stenosis (r = -0.62, r = -0.49, r = -0.51, and r = -0.46, respectively, P < 0.05 for all). Basal tubular fluid concentration capacity and stenotic cortical perfusion response to ACh were both blunted only in ARAS. This study shows that atherosclerosis modulates the impact of a stenosis in the renal artery on stenotic kidney hemodynamics, function, and tubular dynamics. These observations underscore the direct intrarenal effect of atherogenic factors on the kidneys.

Fig. 1.

Renal blood flow (RBF, A), glomerular filtration rate (GFR, B), and cortical (C) and medullary (D) perfusion at baseline (open bars) and in response to ACh (filled bars) in normal, renal artery stenosis (RAS), and atherosclerotic renal artery stenosis (ARAS) kidneys. P < 0.05 vs. baseline (*) and vs. normal (†).

Fig. 2.

Correlation of the renal volume per body wt (vol/BW), GFR, RBF, and cortical and medullary perfusion with the severity of the stenosis in RAS (left) and ARAS (right). All of these functional and hemodynamic parameters correlated better in RAS than in ARAS.

Fig. 3.

Representative renal staining for trichrome and α-smooth muscle actin (top) and quantitation (middle) in normal, RAS, and ARAS stenotic kidneys. Atherosclerosis increased fibrotic changes in ARAS. Bottom: correlation of trichrome staining (indicative of fibrosis content) with RBF (left) and GFR (right) in the stenotic kidney of RAS and ARAS. P < 0.05 vs. normal (*) and vs. RAS (†).