Does Renal Artery Stenting Prevent Clinical Events?

Atherosclerotic renovascular disease (ARVD) continues to pose a thorny challenge for clinicians. ARVD remains themost prevalent cause of renal artery stenosis in Western countries and regularly accompanies disease in other vascular beds, including coronary, cerebral, aortic, and peripheral vessels. Not surprisingly, ARVD is associated with high risk for clinical events, including resistant hypertension, renal insufficiency, pulmonary edema, and other adverse cardiovascular outcomes. It is commonly associated with cardiovascular risk factors, including hypertension, diabetes, dyslipidemias, and tobacco use. For.80 years, reduction in perfusion pressure to the kidney beyond a stenotic lesion has been known to produce hypertension. Much of the initial impetus to revascularize the kidney derived from the failure of early antihypertensive drug therapy to treat renovascular hypertension, classically an angiotensin-dependent model of disease (1,2). Surgical renal revascularization developed as a life-saving maneuver for some malignant forms of hypertension, despite well recognized risks of the procedure itself (3). Remarkably, the recognition that renovascular occlusive disease could produce a reversible loss of kidney function was broadly appreciated only in the 1980s (4,5). Ischemic nephropathy became recognized as anunderdiagnosed form of reversible renal failure, supported by reports of occasional stunning recovery of renal function after revascularization (6). Successful intervention sometimes led to discontinuation of dialytic support. More recently, episodes of circulatory congestion described as flashpulmonary edemahave been recognized as a complication of bilateral ARVD that dramatically resolves after successful renal revascularization (7). For these patients, there is no question that renal revascularization prevents major clinical events. Widespread application ofmore effective antihypertensive drug therapy in the recent era, including agents that block the renin-angiotensin-aldosterone system, hasmade achieving BP goals possible formost patients with ARVD, often for many years. With successful hypertension treatment more often possible, the goal of preserving renal functionbecameaprimarymotivation for renal revascularization for many clinicians. Wider availabilityof sophisticatedvascular andrenal imaging tools and the introduction of endovascular stent procedures expanded the population of patients with ARVD who were considered potential candidates for both medical and interventional treatments, which we have reviewed (2). Application of renal artery stenting expanded rapidly between 1996 and 2005, even for candidates with mild, sometimes incidental, disease (8). However, these procedures introduced substantial costs, and sometimes, they were associated with complications. Some of these were catastrophic, including atheroembolic events, which could worsen kidney function irreversibly. Oneresultof theexpandeduseofvascular intervention for ARVD has been the performance of several prospective, randomized clinical trials (RCTs) to elucidate precisely what benefits endovascular stenting add to medical management. Remarkably, nearly all of these trials have failed to identify much added clinical benefit from renal revascularization, which we and others have reviewed (9,10). Recruitment of patients with clinically significant ARVD to participate in randomized trials has been difficult, however, partly because of the established success of revascularization in patients with extreme cases. This inevitably has resulted in a significant selection bias. The most recent and largest RCT to date was the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) Trial in the United States (11). Results from this trial indicated that stent revascularization did not improve cardiovascular outcomes when added to protocol–driven antihypertensive drug therapy, including an angiotensin receptor blocker (or angiotensinconverting enzyme inhibitor), to target levels combined with statin therapy and appropriate glucose control in patients with diabetes. In this issue of the Clinical Journal of the American Society of Nephrology, Tuttle et al. (12) further report the effects of stenting on eGFR and predictors of clinical events for 931 participants in the CORAL Trial. Entry in this trial depended primarily on showing .60% lumen occlusion of one or more renal arteries. Over the course of enrollment, entry criteria were loosened to allow moderate hypertension (systolic hypertension on two or more drugs, although .25% were at goal BP on entry) and/or mild reductions in eGFR (entry allowed for eGFR,60 ml/min per 1.73 m2), with mean levels of 59624 ml/min per 1.73 m2 at baseline that fell slightly to 55623 ml/min per 1.73 m2 over 3 years for the entire cohort. CKD events were defined as a 30% reduction in eGFR, need for dialysis, renal transplant, or death caused by uremia. Only 8% of subjects had stage 4 CKD (eGFR,30 ml/min per 1.73 m2). Rates of change in eGFR were 21.567 versus 22.36 6.3 ml/min per 1.73 m2 per year in the stented versus Divisions of *Nephrology and Hypertension and Interventional Radiology, Mayo Clinic, Rochester, Minnesota