Damage control for renal artery stenting.

Stenting of atherosclerotic renal artery stenoses is commonly performed in an attempt to preserve renal function and control blood pressure. The number of Medicare recipients undergoing renal artery angioplasty or stent placement has increased strikingly from 7660 cases in 1996 to 18 520 cases in 2000,4 but evidence of benefit remains “sparse and inconclusive.”5 In this issue of Circulation, Cooper and colleagues report the results of a randomized trial of patients undergoing renal artery stenting to determine whether a filter-based embolic protection device (EPD), the platelet glycoprotein inhibitor abciximab, or both in combination improves renal function.6 The results were more negative than anticipated. Glomerular filtration rates (GFR) worsened 30 days after renal stenting in 3 treatment groups and remained unchanged in the fourth group treated with combination therapy (see Table). Secondary comparisons among the treatment groups suggested that the combination of an EPD with abciximab caused the smallest changes in GFR, but no treatment could improve renal function over that existing at baseline before renal artery stenting was carried out. The investigators estimated GFR from the creatinine-based Modification of Diet in Renal Disease formula and corroborated the results with measurements of cystatin C. Cystatin C, a cysteine protease inhibitor produced by nearly all human cells, is a nonglycosylated basic protein with a low molecular mass (13 kDa) that is freely filtered by the glomerulus.7 When Cooper and colleagues used cystatin C to estimate GFR, they observed the same pattern of deterioration in renal function and no significant differences among the treatment groups. Although the current study focused on therapies to prevent microembolism, the results have broader implications. The failure of this well-designed trial6 to achieve its prospectively defined end points challenges some commonly held assumptions about atherosclerotic renal artery disease and the reversibility of renal injury. The study enrolled patients with renal artery stenoses greater than or equal to a 50%-diameter reduction,6 a generally accepted8 but not universally recommended angiographic threshold for stenting.9 The physiological principles defining the minimal critical stenosis needed to reduce perfusion vary from organ to organ. Renal blood flow is 400 mL/min per 100 g of tissue, which is 5 to 50 times more than the flow through other organs, and the arteriovenous oxygen difference is low at 1 to 2 mL/dL.10 In comparison, resting coronary blood flow ranges from 50 to 80 mL/min per 100 g of tissue, and the arteriovenous oxygen difference is high at 16 mL/dL.11 Resting coronary blood flow falls in the presence of an 80% stenosis, but maximal coronary flow reserve begins to fall at about a 50%-diameter stenosis. This is defined as the minimal critical stenosis in the coronary circulation, because flow may need to increase as much as 5-fold when myocardial oxygen consumption rises during exercise.11 The concept of renal flow reserve differs from that for the coronary circulation because oxygen is delivered at rest in marked excess of that required to meet the metabolic needs of the renal parenchyma, and autoregulatory mechanisms increase renal blood flow in the presence of low perfusion pressure.10 In dogs with innervated or denervated kidneys, perfusion pressure falls when diameter stenoses reach 50%.12 Augoregulation of blood flow prevents other functional consequences until stenosis severity exceeds 70%, at which point blood pressure begins to rise (see Figure). Renal blood flow does not fall until stenosis severity is 75%. The threshold stenosis in humans required to reduce renal function remains unknown. In clinical studies, the severity of atherosclerotic stenoses does not correlate with impairments in renal function. Split-kidney measurements in 79 patients with chronic kidney disease, made with a chromium ethylenediamine tetraacetic acid technique, showed that individual kidneys with any severity of stenosis have a GFR the same as or higher than kidneys without a stenosis (17.3 mL/min versus 13.6 mL/min).13 In another study, patients with unilateral or bilateral renal stenoses had similar estimates of GFR (32.1 mL/min versus 32.7 mL/min), and no relation could be identified between stenosis severity and GFR or between stenosis severity and kidney size.14 Although atherosclerotic renal arterial stenoses are commonly associated with evidence of renal impairment, the frequent association does not prove causation. The explanation for the association is clear however: The conditions that cause hypertensive nephrosclerosis and diabetic nephropathy are also common risk factors for the development of atherosclerotic renal artery stenoses.5 Correction of a renal stenosis does not predictably improve renal function, whereas deterioration of function after stenting has potentially dire consequences. Mortality rates at an average of 21 months were The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Munroe Regional Medical Center, Ocala, Fla. Correspondence to John A. Bittl, MD, Ocala Heart Institute, 13013 Hwy 475, Ocala, FL 34480. E-mail [email protected] (Circulation. 2008;117:2724-2726.) © 2008 American Heart Association, Inc.