Urbieta-Caceres VH, Lavi R, Zhu XY, Crane JA, Textor SC, Lerman A, Lerman LO. Early atherosclerosis aggravates the effect of renal artery stenosis on the swine kidney. Am J Physiol Renal Physiol 299: F135-F140, 2010. First published May 12, 2010 doi:10.1152/ajprenal.00159.2010.-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 ϭ Ϫ0.62, r ϭ Ϫ0.49, r ϭ Ϫ0.51, and r ϭ Ϫ0.46, respectively, P Ͻ 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. renovascular hypertension; multidetector CT ATHEROSCLEROTIC RENAL ARTERY stenosis (ARAS) is a common manifestation of generalized atherosclerosis and is the predominant renal arterial lesion in patients over 50 years old (9). ARAS is present in up to 50% of those with atherosclerotic disease elsewhere (10). Moreover, ARAS is an independent risk factor for aggravation of cardiovascular disease (8) and may lead to renovascular hypertension and ischemic nephropathy.While the severity of parenchymal damage in the ischemic ARAS kidney is an important prognostic factor for renal function (24), the degree of the stenosis does not necessarily predict renal hemodynamics and function distal to renal artery stenosis (RAS) (13,20). It is recognized that high-grade atherosclerotic lesions in the renal artery may decrease renal perfusion and impair renal function. Therefore, therapeutic strategies have focused on restoring renal blood supply. However, improvement in blood pressure control or recovery of renal function after renal revascularization are achieved only in selected ARAS patients (22, 23), whereas repair of renal arterial lesions uncomplicated by atherosclerosis often achieves better outcomes (14). These observations suggest that deleterious factors beyond the stenosis, probably triggered by the atherogenic process, play dominant roles in compromising ...