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Background Early rapid declines of kidney function may occur in patients with atherosclerotic renal artery stenosis with institution of medical therapy. The causes and consequences are not well understood. Methods and Results Patients enrolled in the medical therapy-only arm of the CORAL (Cardiovascular Outcomes With Renal Artery Lesions) study were assessed for a rapid decline (RD) in estimated glomerular filtration rate (eGFR), defined as a ≥30% decrease from baseline to either 3 months, 6 months, or both. In the medical therapy-only cohort, eGFR was available in 359 subjects at all time points, the subjects were followed for a median of 4.72 years, and 66 of 359 (18%) subjects experienced an early RD. Baseline log cystatin C (odds ratio, 1.78 [1.11-2.85]; P=0.02), age (odds ratio, 1.04 [1.00-1.07]; P<0.05), and Chronic Kidney Disease Epidemiology Collaboration creatinine eGFR (odds ratio, 1.86 [1.15-3.0]; P=0.01) were associated with an early RD. Despite continued medical therapy only, the RD group had an improvement in eGFR at 1 year (6.9%; P=0.04). The RD and nondecline groups were not significantly different for clinical events and all-cause mortality (P=0.78 and P=0.76, respectively). Similarly, renal replacement therapy occurred in 1 of 66 (1.5%) of the RD patients and in 6 of 294 (2%) of the nondecline patients. The regression to the mean of improvement in eGFR at 1 year in the RD group was estimated at 5.8±7.1%. Conclusions Early rapid declines in kidney function may occur in patients with renal artery stenosis when medical therapy is initiated, and their clinical outcomes are comparable to those without such a decline, when medical therapy only is continued.

Purpose: To perform a post-hoc analysis of the Nephropathy Ischemic Therapy (NITER) trial, which enrolled patients with atherosclerotic renal artery stenosis, to evaluate whether medical therapy plus stent placement is superior to medical therapy alone in patients without elevated albuminuria., Materials and Methods: Data from 51 patients were analyzed and stratified into 2 cohorts by median urinary albumin (UAlb) levels: cohort 1 ("low albuminuria," UAlb ≤0.04 g/24h) and cohort 2 ("high albuminuria," UAlb >0.04g/24h). Interaction effect between treatment arms and UAlb cohorts was calculated using Cox regression analysis. Survival analysis was followed by test for effect size, power analysis, and construction of a Kaplan-Meier survival table., Results: At study completion, 13 patients had an outcome event: 6 (23%) from cohort 1 and 7 (28%) from cohort 2. Patients in cohort 1 had event-free survival of 83% at 3.9 ± 0.3 years from the primary endpoints of all-cause mortality, dialysis, and cardiovascular events when treated with interventional therapy, compared to 45% when treated with medical therapy alone (P = .501), which showed a 62% treatment effect for stent placement. In cohort 2, event-free survival rates were 64% for medical therapy versus 52% for medical plus interventional therapy (P = .64). Using Cox regression analysis, the interaction effect between treatment arms and UAlb cohorts was not significant (P = .32). The power of the study to detect an interaction effect, if one existed, was only 15%., Conclusions: Inference cannot be drawn for similar populations because of inadequate sample size, but, in this sample, patients treated with stent placement who had low albuminuria had better outcomes than patients treated with medical therapy alone., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p<0.001). In addition, patients who smoke were also more likely to have bilateral renal artery stenoses and peripheral vascular disease (PVD). Longitudinal analysis showed that smokers experienced composite endpoint events (defined as first occurrence of: stroke; cardiovascular or renal death; myocardial infarction; hospitalization for congestive heart failure; permanent renal replacement; and progressive renal insufficiency defined as 30% reduction of GFR from baseline sustained for ≥ 60 days) at a substantially younger age compared to non-smokers (67.1±9.0 versus 76.1±7.9, p<0.001). Using linear regression and generalized linear modeling analysis controlled by age, sex, and ethnicity, smokers had significantly higher cystatin C levels (1.3±0.7 vs 1.2±0.9, p<0.01) whereas creatinine and estimated glomerular filtration rate (eGFR) were not different from non-smokers. From these data we conclude that smoking has a significant association with deleterious cardio-renal outcomes in patients with renovascular hypertension.

Randomized clinical trials have not shown an additional clinical benefit of renal artery stent placement over optimal medical therapy alone. However, studies of renal artery stent placement have not examined the relationship of albuminuria and treatment group outcomes. The CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) is a prospective clinical trial of 947 participants with atherosclerotic renal artery stenosis randomized to optimal medical therapy with or without renal artery stent which showed no treatment differences (3(5.8% and 35.1% event rate at mean 43-month follow-up). In a post hoc analysis, the study population was stratified by the median baseline urine albumin/creatinine ratio (n=826) and analyzed for the 5-year incidence of the primary end point (myocardial infarction, hospitalization for congestive heart failure, stroke, renal replacement therapy, progressive renal insufficiency, or cardiovascular disease- or kidney disease-related death), for each component of the primary end point, and overall survival. When baseline urine albumin/creatinine ratio was ≤ median (22.5 mg/g, n=413), renal artery stenting was associated with significantly better event-free survival from the primary composite end point (73% versus 59% at 5 years; P=0.02), cardiovascular disease-related death (93% versus 85%; P≤ 0.01), progressive renal insufficiency (91% versus 77%; P=0.03), and overall survival (89% versus 76%; P≤0.01), but not when baseline urine albumin/creatinine ratio was greater than median (n=413). These data suggest that low albuminuria may indicate a potentially large subgroup of those with renal artery stenosis that could experience improved event-free and overall-survival after renal artery stent placement plus optimal medical therapy compared with optimal medical therapy alone. Further research is needed to confirm these preliminary observations., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00081731., (© 2016 American Heart Association, Inc.)

Background and Objectives: Atherosclerotic renal artery stenosis may cause kidney function loss, but effects of stenting on eGFR and clinical events associated with CKD are uncertain. Our study objectives were to determine effects of stenting on eGFR and predictors of clinical events., Design, Setting, Participants, & Measurements: Participants (n=931) in the Cardiovascular Outcomes in Renal Artery Stenosis Trial (from May of 2005 to September of 2012) had >60% atherosclerotic renal artery stenosis and systolic hypertension on two or more antihypertensive drugs and/or stage ≥3 CKD. The intervention was stenting versus no stenting on a background of risk factor management: renin-angiotensin system inhibition, statin, antiplatelet therapy, and smoking cessation education. The effect of stenting on eGFR by the serum creatinine-cystatin C Chronic Kidney Disease Epidemiology Collaboration equation was the prespecified analysis of kidney function. Predictors of eGFR and CKD outcomes (≥30% eGFR loss, ESRD, and death) and cardiovascular disease outcomes (stroke, myocardial infarction, heart failure, and death) controlling for eGFR and albuminuria were also determined., Results: eGFR was 59±24 ml/min per 1.73 m(2) (mean±SD) at baseline. Over 3 years, eGFR change, assessed by generalized estimating equations, was -1.5±7.0 ml/min per 1.73 m(2) per year in the stent group versus -2.3±6.3 ml/min per 1.73 m(2) per year in the medical therapy only group (P=0.18). eGFR predictors (multiple variable generalized estimating equations) were age, albuminuria, systolic BP, and diabetes (inverse associations) as well as men, total cholesterol, and HDL cholesterol (positive associations). CKD outcomes events occurred in 19% (175 of 931), and predictors (Cox proportional hazards models) included albuminuria (positive association), systolic BP (positive association), and HDL cholesterol (inverse association). Cardiovascular disease outcomes events occurred in 22% (207 of 931), and predictors included age, albuminuria, total cholesterol, prior cardiovascular disease, and bilateral atherosclerotic renal artery stenosis (positive associations)., Conclusions: Stenting did not influence eGFR in participants with atherosclerotic renal artery stenosis receiving renin-angiotensin system inhibition-based therapy. Predictors of clinical events were traditional risk factors for CKD and cardiovascular disease., (Copyright © 2016 by the American Society of Nephrology.)

Background: Multiple randomized clinical trials comparing renal artery stent placement plus medical therapy with medical therapy alone have not shown any benefit of stent placement. However, debate continues whether patients with extreme pressure gradients, stenosis severity, or baseline blood pressure benefit from stent revascularization., Objectives: The study sought to test the hypothesis that pressure gradients, stenosis severity, and/or baseline blood pressure affects outcomes after renal artery stent placement., Methods: Using data from 947 patients with a history of hypertension or chronic kidney disease from the largest randomized trial of renal artery stent placement, the CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) study, we performed exploratory analyses to determine if subsets of patients experienced better outcomes after stent placement than the overall cohort. We examined baseline stenosis severity, systolic blood pressure, and translesion pressure gradient (peak systolic and mean) and performed interaction tests and Cox proportional hazards analyses for the occurrence of the primary endpoint through all follow-up, to examine the effect of these variables on outcomes by treatment group., Results: There were no statistically significant differences in outcomes based on the examined variables nor were there any consistent nonsignificant trends., Conclusions: Based on data from the CORAL randomized trial, there is no evidence of a significant treatment effect of the renal artery stent procedure compared with medical therapy alone based on stenosis severity, level of systolic blood pressure elevation, or according to the magnitude of the trans-stenotic pressure gradient. (Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions [CORAL]; NCT00081731)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

For people enrolled in Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL), we sought to examine whether variation exists in the baseline medical therapy of different geographic regions and if any variations in prescribing patterns were associated with physician specialty. Patients were grouped by location within the United States (US) and outside the US (OUS), which includes Canada, South America, Europe, South Africa, New Zealand, and Australia. When comparing US to OUS, participants in the US took fewer anti-hypertensive medications (1.9 ± 1.5 vs. 2.4 ± 1.4; P < .001) and were less likely to be treated with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (46% vs. 62%; P < .001), calcium channel antagonist (37% vs. 58%; P < .001), and statin (64% vs. 75%; P < .05). In CORAL, the identification of variations in baseline medical therapy suggests that substantial opportunities exist to improve the medical management of patients with atherosclerotic renal-artery stenosis., (Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Renal artery fibromuscular dysplasia (FMD) may be underdiagnosed. We evaluated the prevalence of FMD in CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) renal artery stent trial participants, in which FMD was an exclusion criterion for inclusion. We also evaluated the prevalence of FMD in a relatively healthy population of patients undergoing computed tomographic angiographic (CTA) screening for renal donor evaluation. All renal donor CTAs performed at our institution from January 2003 through November 2011 were retrospectively reviewed for the presence of FMD along with patient sex and age. These results were compared to angiographic core lab (ACL) findings for the CORAL trial. The CORAL ACL database contained 997 patients (mean age 69.3 years; 50% female). Fifty-eight (5.8%) CORAL trial patients (mean age 71.8 years; 75.9% female) demonstrated incidental FMD. The renal donor cohort included 220 patients (mean age 40.5 years; 64.5% female). Five (2.3%) demonstrated FMD (mean age 48.6 years; all female). The odds of FMD in the CORAL cohort were 2.65 times that seen in the renal donor cohort (95% CI: 1.12, 7.57). In C: onclusion, the 5.8% prevalence of renal artery FMD in the CORAL trial population, the presence of which was biased against, suggests underdiagnosis., (© The Author(s) 2014.)

Background and Objectives: People with atherosclerotic renal artery stenosis may benefit from renin-angiotensin inhibitors, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers, but little is known about the factors associated with their use., Design, Setting, Participants, & Measurements: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions study (ClinicalTrials.gov identified: NCT00081731) is a prospective, international, multicenter clinical trial that randomly assigned participants with atherosclerotic renal artery stenosis who received optimal medical therapy to stenting versus no stenting from May 2005 through January 2010. At baseline, medication information was available from 853 of 931 randomly assigned participants. Kidney function was measured by serum creatinine-based eGFR at a core laboratory., Results: Before randomization, renin-angiotensin inhibitors were used in 419 (49%) of the 853 participants. Renin-angiotensin inhibitor use was lower in those with CKD (eGFR<60 ml/min per 1.73 m(2)) (58% versus 68%; P=0.004) and higher in individuals with diabetes (41% versus 27%; P<0.001). Presence of bilateral renal artery stenosis or congestive heart failure was not associated with renin-angiotensin inhibitor use. Although therapy with renin-angiotensin inhibitors varied by study site, differences in rates of use were not related to the characteristics of the site participants. Participants receiving a renin-angiotensin inhibitor had lower systolic BP (mean ± SD, 148 ± 23 versus 152 ± 23 mmHg; P=0.003) and more often had BP at goal (30% versus 22%; P=0.01)., Conclusions: Kidney function and diabetes were associated with renin-angiotensin inhibitor use. However, these or other clinical characteristics did not explain variability among study sites. Patients with renal artery stenosis who received renin-angiotensin inhibitor treatment had lower BP and were more likely to be at treatment goal., (Copyright © 2014 by the American Society of Nephrology.)

Purpose: To describe the experience and results from the roll-in phase of the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study., Materials and Methods: The CORAL roll-in database was used to describe the baseline characteristics of the patients in the roll-in cohort, all of whom underwent renal artery stent placement; to evaluate CORAL site performance; to compare estimates of lesion (stenosis) severity made by site interventionalists with the central CORAL angiographic core laboratory readings; and to report outcomes after renal artery stent placement. During the roll-in phase, 239 patients (mean age, 70.2 y ± 9.0; 49% male) underwent renal artery stent procedures. Angiographic core laboratory analysis of renal arteriograms was done, and participants were followed at 1 month and 9 months., Results: Major angiographic complications were identified in 28 (13%) subjects. Kidney function remained unchanged at the short (2-4 weeks) follow-up interval. Improvement in systolic blood pressure with use of distal embolic protection devices (n = 161) did not show any clinical benefit over nonuse of such devices (n = 78) in this small series. At 9 months, there were significantly more endpoints reported by site in subjects with bilateral renal artery stenosis (P = .01) and prior history of stroke (P = .03)., Conclusions: In the roll-in phase of the CORAL study, a significant number of angiographic complications were identified. No effect was seen on estimated glomerular filtration rate after renal artery stent placement, but systolic blood pressure decreased significantly., (© 2013 Published by SIR on behalf of The Society of Interventional Radiology.)

Background: Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain., Methods: We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy)., Results: Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03)., Conclusions: Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.).

Background: Preservation of renal function is an important objective of renal artery stent procedures. Although atheroembolization can cause renal dysfunction during renal stent procedures, whether adjunctive use of embolic protection devices or glycoprotein IIb/IIIa inhibitors improves renal function is unknown., Methods and Results: One hundred patients undergoing renal artery stenting at 7 centers were randomly assigned to an open-label embolic protection device, Angioguard, or double-blind use of a platelet glycoprotein IIb/IIIa inhibitor, abciximab, in a 2x2 factorial design. The main effects of treatments and their interaction were assessed on percentage change in Modification in Diet in Renal Disease-derived glomerular filtration rate from baseline to 1 month using centrally analyzed creatinine. Filter devices were analyzed for the presence of platelet-rich thrombus. With stenting alone, stenting and embolic protection, and stenting with abciximab alone, glomerular filtration rate declined (P<0.05), but with combination therapy, it did not decline and was superior to the other allocations in the 2x2 design (P<0.01). The main effects of treatment demonstrated no overall improvement in glomerular filtration rate; although abciximab was superior to placebo (0+/-27% versus -10+/-20%; P<0.05), embolic protection was not (-1+/-28% versus -10+/-20%; P=0.08). An interaction was observed between abciximab and embolic protection (P<0.05), favoring combination treatment. Abciximab reduced the occurrence of platelet-rich emboli in the filters from 42% to 7% (P<0.01)., Conclusions: Renal artery stenting alone, stenting with embolic protection, and stenting with abciximab were associated with a decline in glomerular filtration rate. An unanticipated interaction between Angioguard and abciximab was seen, with combination therapy better than no treatment or either treatment alone.

Renal artery stenosis (RAS) is usually caused by atherosclerosis or fibromuscular dysplasia. RAS leads to activation of the renin-angiotensin-aldosterone system and may result in hypertension, ischemic nephropathy, left ventricular hypertrophy and congestive heart failure. Management options include medical therapy and revascularization procedures. Recent studies have shown angiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACE-I) to be highly effective in treating the hypertension associated with RAS and in reducing cardiovascular events; however, they do not correct the underlying RAS and loss of renal mass may continue. Renal artery angioplasty was first performed by Gruntzig in 1978. The routine use of stents has increased technical success rates compared with angioplasty, and surgery is now only rarely performed. Although numerous case series claimed benefit in terms of blood pressure control, no adequately powered randomized, controlled, prospective study of renal artery interventions has reported their effect on cardiovascular morbidity or mortality. The CORAL trial, an ongoing study of renal artery stent placement and optimal medical therapy (OMT) funded by the National Institutes of Health, is the first study to attempt to do so. Until the CORAL trial results are in, physicians will continue to be faced with difficult choices when determining the optimal management for RAS patients and deciding which, if any, patients should be offered revascularization.

Distal or embolic protection has intuitive appeal for its potential to prevent embolization of materials generated during interventional procedures. Distal protection devices (DPDs) have been most widely used in the coronary and carotid vascular beds, where they have demonstrated the ability to trap embolic materials and, in some cases, to reduce complications. Given the frequency of chronic kidney disease in patients with renal artery stenosis undergoing stent placement, it is reasonable to propose that these devices may play an important role in limiting distal embolization in the renal vasculature. Careful review of the literature reveals that atheroembolization does occur during renal arterial interventions, although it often goes undetected. Early experience with DPDs in the renal arteries in patients with suitable anatomy suggests retrieval of embolic materials in approximately 71% of cases and renal functional improvement/stabilization in 98% of cases. The combination of platelet inhibition and a DPD may provide even greater benefit. Given the critical importance of renal functional preservation, it follows that everything that can be done to prevent atheroembolism should be undertaken including the use of DPDs when anatomically feasible. The data available at this time support a beneficial role for these devices.

Background: Atherosclerotic renal artery stenosis is a problem with no consensus on diagnosis or therapy. The consequences of renal ischemia are neuroendocrine activation, hypertension, and renal insufficiency that can potentially result in acceleration of atherosclerosis, further renal dysfunction, myocardial infarction, heart failure, stroke, and death. Whether revascularization improves clinical outcomes when compared with optimum medical therapy is unknown., Methods: CORAL is a randomized clinical trial contrasting optimum medical therapy alone to stenting with optimum medical therapy on a composite cardiovascular and renal end point: cardiovascular or renal death, myocardial infarction, hospitalization for congestive heart failure, stroke, doubling of serum creatinine, and need for renal replacement therapy. The secondary end points evaluate the effectiveness of revascularization in important subgroups of patients and with respect to all-cause mortality, kidney function, renal artery patency, microvascular renal function, and blood pressure control. We will also correlate stenosis severity with longitudinal renal function and determine the value of stenting from the perspectives of quality of life and cost-effectiveness. The primary entry criteria are (1) an atherosclerotic renal stenosis of > or = 60% with a 20 mm Hg systolic pressure gradient or > or = 80% with no gradient necessary and (2) systolic hypertension of > or = 155 mm Hg on > or = 2 antihypertensive medications. Randomization will occur in 1080 subjects. The study has 90% power to detect a 28% reduction in primary end point hazard rate., Conclusions: CORAL represents a unique opportunity to determine the incremental value of stent revascularization, in addition to optimal medical therapy, for the treatment of atherosclerotic renal artery stenosis.

Objective: Digital subtraction angiography quantitative vessel analysis (QVA) to assess percent renal arterial stenosis (RAS) is the reference standard. Quantitative vessel analysis is not ideal for screening purposes. Renal artery duplex ultrasonography (RADUS) is a noninvasive method to screen for RAS using well-known parameters. We investigated the direct correlation between several RADUS parameters and QVA to evaluate the acceptability of RADUS as a RAS screening and surveillance tool., Methods: We performed a multicenter retrospective study. Stenoses were evaluated in all patients with arteriograms and RADUS examinations within 30 days of each other in the span of 1 year. Percent stenosis of each stenotic renal artery segment was calculated digitally with QVA and correlated with the corresponding peak systolic velocity (PSV) and renal-aortic ratio (RAR) obtained with RADUS. Descriptive statistics and receiver operating characteristic curves were calculated. Correlation of percent stenosis, PSV, and RAR was performed. Sensitivity, specificity, and accuracy of diagnostic cut points for each RADUS parameter were calculated., Results: Sixty-seven renal arteries were included. Thirty-three arteries had less than 60% stenosis; 34 had stenosis of 60% or greater. The mean values were PSV, 272.791 cm/s; RAR, 3.716; and angiographic percent stenosis, 51.731%. Receiver operating characteristic curves showed higher accuracy for RAR with stenoses of 60% or greater versus PSV., Conclusions: Renal artery duplex ultrasonographic parameters for 60% or greater RAS correlate well with QVA. For detecting stenosis of 60% or greater, RAR is the most accurate parameter at a threshold of 2.5. Renal-aortic ratio is more accurate than PSV. Peak systolic velocity may be a useful RADUS alternative parameter for hemodynamically important stenoses in the setting of aortic disease when aortic velocities are less than 40 or greater than 100 cm/s.

Chronic renal ischemia caused by atherosclerotic renal artery stenosis (RAS) is gaining recognition as a potentially important risk factor for cardiovascular (CV) morbidity and mortality. The etiology of increased risk of CV events is multifaceted and includes direct physiologic changes that increase risk as well as intermediate clinical effects that are associated with worse outcome. Physiologic changes associated with increased CV risk in patients with RAS include increased production of fibrogenic and vasoactive peptides such as renin, angiotensin, endothelin, and catecholamines, as well as endothelial cell dysfunction. Clinical intermediate conditions associated with higher incidences of CV events seen in patients with renal ischemia include hypertension, systemic atherosclerosis, chronic renal failure, and left ventricular hypertrophy and dysfunction. More thorough understanding of the myriad physiologic changes seen in patients with RAS will likely improve patient selection for renal artery revascularization. Clinical trials should examine a full range of CV and renal outcomes, not just blood pressure, to adequately assess the merits of revascularization.

Chronic renal ischemia caused by renal artery stenosis (RAS) elicits a complex biologic response. Although the traditional pathophysiologic pathways underlying renal ischemia have been well studied, there is emerging evidence that additional mechanisms may be responsible for producing many of the hemodynamic alterations and end-organ injury seen in patients with RAS, including persistent hypertension, renal insufficiency, and cardiac disturbance syndromes. A better understanding of these mechanisms may allow earlier identification of RAS, provide markers to predict the response to revascularization, or allow unique therapeutic targets for drug development. This and a subsequent article will explore the pathophysiologic and clinical implications of chronic renal ischemia.