Atherosclerotic Renal Artery Disease Research Articles

Approach to Renovascular Hypertension

ABSTRACT The article describes the case of a 68-year-old man with poorly controlled hypertension, diabetes, and coronary artery disease, highlighting potential underlying causes of his condition, particularly secondary hypertension due to renal artery stenosis. His clinical evaluation reveals risk factors such as prolonged smoking, obesity, and peripheral vascular disease. Clinical examinations indicate significant blood pressure discrepancies between limbs and the presence of renal bruits, leading to the suspicion of renovascular hypertension. Resistant hypertension can often stem from renal causes, specifically atherosclerotic renal artery disease. Diagnostic approaches are detailed, including various imaging techniques and criteria for assessing renal artery stenosis. Management options are discussed, exploring both medical and interventional therapies. Although recent trials like ASTRAL, CORAL, and STAR showed limited benefits of revascularisation over medical management, selected patients may still benefit from intervention. The case underscores the importance of individualised patient evaluation for managing secondary hypertension and renovascular disease, considering both clinical presentation and renal parenchymal viability.

Endovascular interventions in symptomatic atherosclerotic renal artery disease

Endovascular interventions in symptomatic atherosclerotic renal artery disease

Inflammation and Oxidative Damage in Ischaemic Renal Disease.

Ischaemic renal disease as result of atherosclerotic renovascular disease activates a complex biological response that ultimately leads to fibrosis and chronic kidney disease. Large randomised control trials have shown that renal revascularisation in patients with atherosclerotic renal artery disease does not confer any additional benefit to medical therapy alone. This is likely related to the activation of complex pathways of oxidative stress, inflammatory cytokines and fibrosis due to atherosclerotic disease and hypoxic injury due to reduced renal blood flow. New evidence from pre-clinical trials now indicates a role for specific targeted therapeutic interventions to counteract this complex pathogenesis. This evidence now suggests that the focus for those with atherosclerotic renovascular disease should be a combination of revascularisation and renoprotective therapies that target the renal tissue response to ischaemia, reduce the inflammatory infiltrate and prevent or reduce the fibrosis.

Coexistent atherosclerotic renal artery and lower limb peripheral artery disease in patients with symptomatic triple vessel coronary artery disease

Coexistent atherosclerotic renal artery and lower limb peripheral artery disease in patients with symptomatic triple vessel coronary artery disease

AIUM Practice Parameter for the Performance of Duplex Sonography of Native Renal Vessels

AIUM Practice Parameter for the Performance of Duplex Sonography of Native Renal Vessels

Blood pressure decreases after revascularization in atherosclerotic renal artery disease: A cohort study based on a multidisciplinary meeting

BackgroundIn atherosclerotic renal artery disease, the benefit of revascularization is controversial. A clinical decision-making process based on a multidisciplinary meeting was formalized in the Lyon university hospital.ObjectivesTo investigate whether this decisional process ensured a clinical benefit to patients assigned to renal revascularization.MethodsSingle-centre retrospective cohort study, including patients diagnosed from April 2013 to February 2015 with an atherosclerotic renal artery disease with a peak systolic velocity >180cm/s. For each patient, the decision taken in multidisciplinary meeting (medical treatment or revacularization) was compared to the one guided by international guidelines. Blood pressure values, number of antihypertensive medications, presence of an uncontrolled or resistant hypertension, and glomerular filtration rate at one-year follow-up were compared to baseline values. Safety data were collected.ResultsForty-nine patients were included: 26 (53%) were assigned to a medical treatment and 23 (47%) to a renal revascularization. Therapeutic decision was in accordance with the 2013 American Health Association guidelines and with the 2017 European Society of Cardiology guidelines for 78% and 22% of patients who underwent revascularization, respectively. Patients assigned to revascularization presented a significant decrease in systolic blood pressure (-23±34mmHg, p = 0.007), diastolic blood pressure (-12±18mmHg, p = 0.007), number of antihypertensive medications (-1.00±1.03, p = 0.001), and number of uncontrolled or resistant hypertension (p = 0.022 and 0.031) at one-year follow-up. Those parameters were not modified among patients assigned to medical treatment alone. There was no grade 3 adverse event.ConclusionBased on a multidisciplinary selection of revascularization indications, patients on whom a renal revascularization was performed exhibited a significant improvement of blood pressure control parameters with no severe adverse events.

Cardiac function response to stenting in atherosclerotic renal artery disease with and without heart failure: results from the Carmel study.

AimsConsensus‐derived guidelines recommend renal stenting for patients with atherosclerotic renal artery disease (ARAD) and heart failure (HF). The aim of this prospective multi‐centre observational study was to verify our hypothesis that changes in E/e′, an echocardiographic correlate of left ventricular (LV) filling pressure, following renal stenting may differ between ARAD patients with and without HF.Methods and resultsThis study enrolled de novo ARAD patients undergoing renal stenting at 14 institutions. The primary endpoint was the difference in E/e′ change between ARAD patients with and without HF. Clinical and echocardiographic data were prospectively collected at baseline, the day following renal stenting, and 1 month and 6 months afterwards. ARAD patients with HF were defined as patients with New York Heart Association (NYHA) Class 2 and more, or a history of HF hospitalization. A total of 76 patients were included, and 39% were ARAD patients with HF. ARAD patients with HF had significantly lower estimated glomerular filtration rate (P = 0.028) and higher NYHA functional class (P < 0.001) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score (P = 0.001) than ARAD patients without HF. Also, ARAD patients with HF had significantly lower LV ejection fraction (P = 0.003) and e′‐velocity (P = 0.003) and higher E/e′ ratio (P = 0.001), left atrial volume index (LAVI) (P = 0.046), LV end‐diastolic volume (LVEDV) (P = 0.001), LV end‐systolic volume (LVESV) (P = 0.001), and LV mass index (P = 0.009) than ARAD patients without HF. All procedures were successful. In contrast to blood pressure and renal function, there was a significant interaction in E/e′ (P interaction < 0.001) between time and HF, and ARAD patients with HF showed a significant (P < 0.001) decrease in E/e′ albeit those without HF. By the same token, there was a significant interaction in NYHA class (P interaction < 0.001), MLHFQ score (P interaction = 0.018), E‐velocity (P interaction = 0.002), LAVI (P interaction = 0.001), LVEDV (P interaction = 0.003), and LVESV (P interaction = 0.001) between time and HF with a significant improvement in all these variables in ARAD patients with HF (NYHA class, P = 0.001; MLHFQ score, P = 0.002; E‐velocity, P = 0.005; LAVI, P = 0.001; LVEDV, P = 0.017; and LVESV, P = 0.011).ConclusionsChange in LV filling pressure after renal stenting differed between ARAD patients with and without HF, with a significant improvement in LV filling pressure in patients with HF‐ARAD. These unique findings might support clinical cardiac benefits of renal stenting in ARAD patients with HF.

Abstract 16991: Relationship Between Restenosis After Percutaneous Transluminal Renal Angioplasty for Atherosclerotic Renal Artery Disease and the Preprocedural Renal Resistance Index in the Contralateral Kidney

Introduction: Percutaneous transluminal renal angioplasty (PTRA) is an established treatment for atherosclerotic renal artery disease. Renal resistive index (RRI) is known as an indicator of renovascular atherosclerosis, and several studies reported that high preoperative RRI in the target kidney predicts poor response in hemodynamics and renal function after PTRA. However, RRI is elevated not as a sequence of proximal renal artery stenosis, and relationship between the patency after PTRA and RRI still has not been clarified. Methods: The CARMEL study (Cardiac Benefits of Renal Artery Stenting: A Prospective Multicenter Observational study) is a study of patients with de novo symptomatic ARAD who underwent PTRA between September 2012 and December 2015 at 14 institutions in Japan. Of the 76 patients who included in the final analysis of the CARMEL study, 46 patients (71.8±9.9 years) whose bilateral RRI were recorded before PTRA procedure were retrospectively analyzed. We evaluated renal ultrasonographic data collected before PTRA, and at 1-day, 1-month and 6-month follow-up. Results: 55 lesions of the 46 patients were treated, and preprocedural RRI in the target kidney (tRRI) were higher than 0.8 in 16 lesions (High-tRRI group) and preprocedural RRI in the contralateral kidney (cRRI) were higher than 0.8 in 18 lesions (High-cRRI group). Preprocedural peak systolic velocity (PSV) and renal/aorta ratio (RAR) of the lesions were comparable between High-tRRI group and the rest, and also between High-cRRI group and the rest. However, in High-cRRI group, PSV of the target lesion is significantly higher than the rest at every follow up exam (at 6-month follow up: PSV 224.4±126.5 cm/s vs 113.7±53.7 cm/s, p&amp;lt;0.001; RAR 3.91±2.68 vs 1.99±1.07, p=0.009). (Table 1, Table 2) Conclusion: High preprocedural RRI in the contralateral kidney could be a predictor of restenosis after PTRA.

Predictors of cardiac benefits of renal artery stenting from a multicentre retrospective registry

ObjectivesThere have been limited data regarding the prediction of cardiac benefits after renal artery stenting for patients with atherosclerotic renal artery disease (ARAD). The aim of this multicentre retrospective study...

To Stent or Not to Stent? Update on Revascularization for Atherosclerotic Renovascular Disease.

Renal artery stenosis (RAS) is increasingly encountered in clinical practice. The two most common etiologies are fibromuscular dysplasia (FMD) and atherosclerotic renal artery disease (ARAS), with the latter accounting for the vast majority of cases. Significant RAS activates the renin-angiotensin-aldosterone system and is associated with three major clinical syndromes: ischemic nephropathy, hypertension, and destabilizing cardiac syndromes. Over the past two decades, advancements in diagnostic and interventional techniques have led to improved detection and the widespread use of endovascular renal artery revascularization strategies in the management of ARAS. However, renal artery stenting for ARAS remains controversial. Although several studies have demonstrated some benefit with renal artery revascularization, this has not been to the extent anticipated or predicted. Moreover, these trials have significant flaws in their study design and are hampered with inherent bias which make their interpretation challenging. In this review, we evaluate the existing body of evidence and offer an approach to the management of patients with ARAS in light of the current literature. From the data provided, identification of subgroup of patients, namely, those with a hemodynamically significant RAS in the context of progressive renal insufficiency and/or deteriorating arterial hypertension, seems possible and may derive clinical benefit from ARAS stent revascularization. Appropriate patient selection is therefore the key and more robust studies are required.

Renovascular heart failure: heart failure in patients with atherosclerotic renal artery disease.

Atherosclerotic renal artery disease presents with a broad spectrum of clinical features, including heart failure as well as hypertension, and renal failure. Although recent randomized controlled trials failed to demonstrate renal artery stenting can reduce blood pressure or the number of cardiovascular or renal events more so than medical therapy, increasing attention has been paid to flash pulmonary edema and congestive heart failure associated with atherosclerotic renal artery disease. This clinical entity "renovascular heart failure" is diagnosed retrospectively. Given the increasing global burden of heart failure, this review highlights the background and catheter-based therapeutic aspects for renovascular heart failure.

THE RELATIONSHIP BETWEEN RENAL ARTERY STENOSIS AND ISCHEMIC NEPHROPATHY

Article type Review article Article history Ischemic nephropathy is defined as a clinically significant progressive reduction in glomerular filtration rate that is usually associated with significant renal artery stenosis (unilateral or bilateral involvement). Atherosclerotic renal artery disease is known as the most common cause of the ischemic nephropathy. These patients may develop secondary hypertension. In addition, epidemiologic data has showed a clear association between atherosclerotic renal artery stenosis and coronary artery disease and other cardiovascular disease. Despite the preserving function of kidney on various autoregulation processes, unusual microvascular function will be resulted due to sustained decline in renal perfusion. The ischemic nephropathy of asymptomatic cases may result in renovascular hypertension and renal failure. The reduction of renal function in these patients might be decreased or stopped by early appropriate diagnosis and also might be treated with renal artery angioplasty or surgery, after medical management. There is a debate about the occurrence of ischemic nephropathy as a result of atherosclerotic renal artery stenosis. In this study we aimed to review the prevalence of ischemic nephropathy due to atherosclerotic renal artery stenosis.

Renal artery stenosis: epidemiology and treatment.

Renal artery stenosis (RAS) is a frequently encountered problem in clinical practice. The disease encompasses a broad spectrum of pathophysiologies and is associated with three major clinical syndromes: ischemic nephropathy, hypertension, and destabilizing cardiac syndromes. The two most common etiologies are fibromuscular dysplasia and atherosclerotic renal artery disease with atherosclerotic disease accounting for the vast majority of cases. Atherosclerotic renovascular disease has considerable overlap with atherosclerotic disease elsewhere and is associated with a poor prognosis. A wide range of diagnostic modalities and treatment approaches for RAS are available to clinicians, and with the advent of endovascular interventions, selecting the best course for a given patient has only grown more challenging. Several clinical trials have demonstrated some benefit with revascularization but not to the extent that many had hoped for or expected. Furthermore, much of the existing data is only marginally useful given significant flaws in study design and inherent bias. There remains a need for further identification of subgroups and appropriate indications in hopes of maximizing outcomes and avoiding unnecessary procedures in patients who would not benefit from treatment. In recent decades, the study of RAS has expanded and evolved rapidly. In this review, we will attempt to summarize the amassed body of literature with a focus on the epidemiology of RAS including prevalence, overlap with other atherosclerotic disease, and prognosis. We will also outline existing diagnostic and treatment approaches available to clinicians as well as summarize the findings of several major clinical trials. Finally, we will offer our perspective on future directions in the field.

Long-term follow-up of patients with atherosclerotic renal artery disease

Atherosclerotic renal artery stenosis (ARAS) is a predictor of increased morbidity and mortality. However, whether ARAS itself accelerates the arteriosclerotic process or whether ARAS is solely the consequence of atherosclerosis is unclear. We imaged renal arteries of 1561 hypertensive patients undergoing coronary angiography and followed this cohort for 9 years (range, 2.4–15.1 years; median, 31.2 months, interquartile range, 13.4/52.9 months). All patients received aspirin, renin-angiotensin system blockade, statins, and beta blockade as indicated. One hundred seventy-one patients had ARAS >50% diameter stenosis and 126 patients an arteriosclerotic plaque (ARAP) without significant stenosis. Blood pressures were not different in ARAS, ARAP, and non-ARAS patients. After adjustment for cardiovascular risk factors by propensity scores and matched pair analysis, ARAS patients had a lower ejection fraction and more coronary artery disease (CAD) than non-ARAS patients. The same was true for brain natriuretic peptide values, troponin I, and highly sensitive C-reative protein. Over 9 years, more ARAS patients died of any cause (34% vs 23%; P < .05). The prevalence of CAD in ARAP patients was higher than in non-ARAS patients and lower than in ARAS patients. The mortality of the ARAP patients at 9 years was 37%, not different from the ARAS patients. Atherosclerotic renal artery disease appears to be a marker for the severity of atherosclerosis rather than a causative factor for atherosclerosis progression.

Prospective monitoring N-terminal pro-brain natriuretic peptide during natural progression of atherosclerotic renal artery stenosis in elderly

Prognostic values of N-terminal pro-brain natriuretic peptide (NT-proBNP) in myriad diseases have been studied. During the natural progression of atherosclerotic renal artery disease (ARVD) changes of NT-proBNP levels and its significance is not understood. A prospective longitudinal follow-up study was conducted among 61 ARVD patients (77.7±5.2 years old). NT-proBNP was determined at baseline and six month intervals over 25.89±12.44 months and its correlation with death and/or newly occurred CVEs were assessed. Level of NT-proBNP increased from baseline median 210.0pg/mL (25th–75th percentile, 98.0pg/mL–540.0pg/mL) to 900.9pg/mL (25th–75th percentile, 704.5pg/mL–1583.5pg/mL) (p=0.032) at the end of follow-up. Among 44.26% of the cohort (n=27) NT-proBNP level ≥450pg/mL was detected, which 6 deaths happened (22.22% death rate) and CVEs occurred to 62.96% of patients, comparing to 0% death rate (p=0.077) and 8.82% affected by CVEs (p=0.019) in other 55.74% of cohort (n=34) whose NT-proBNP <450pg/mL. Kaplan–Meier analysis showed that NT-proBNP level ≥450pg/mL was a risk factor related to CVEs (HR=3.96, p=0.03). Cox regression analysis found NT-proBNP level ≥450pg/mL was an independent risk factor of CVEs (HR=5.12, p=0.022) after adjustment of body mass index, blood pressure, kidney function. The negative predictive value was 90.9% of NT-proBNP levels ≥450pg/mL for new CVEs. NT-proBNP levels diverge throughout ARVD natural progression in elderly males over 75 years of age. Elevated NT-proBNP level of ≥450pg/mL was predictive for CVEs with 90.9% of negative predictive value.

Cryo-treatment of the renal nerve to the clipped kidney in 2K1C Hypertensive rats: Hemodynamic and neural responses

R renal denervation (DNX) is gaining increasing interest as a modality for treating resistant hypertension. The two-kidney one-clip (2K1C) hypertensive rat is a model of renovascular hypertension. In addition to activation of the reninangiotensinsystem, 2K1C rats display elevated sympathetic activity. Earlier work reported that surgical renal denervation (DNX) decreases mean arterial pressure (MAP) in this model. Since radiofrequency ablation may be problematic in atherosclerotic renal artery disease, we hypothesized that cryo-treatment of the renal nerve to the clipped kidney of 2K-1C rats would decrease MAP, decrease contralateral renal sympathetic nerve activity (RSNA), and improve baroreflex sensitivity. Male Sprague-Dawley rats had sham (SC) or right renal artery clipping (2K1C) and hemodynamic monitoring by telemetry. They were pair fed a 0.4% NaCl diet. Six weeks later,2K1C rats were stratified to moderate (MAP≥140 mmHg) or mild (MAP<140 mmHg) hypertension, instrumentedand underwent sham-DNX or cryo-DNX. All rats were studied in the conscious state. MAP decreased by 16±5 mmHg in the 2K1C cryo-DNXmoderate hypertension group (P<0.05). Cryo-DNX exerted only a small depressor effect in mildly hypertensive 2K1C rats. In the moderately hypertensive 2K1C cryo-DNX rats, contralateral RSNA decreased from 12.2±1.5 to 3.1±3.5 μV.s (P<0.05), a value no different from SC rats 3.3 μV.s. Baroreflex sensitivity of both heart rate and RSNA increased in the cryo-DNX 2K1C rats. Renal tissue norepinephrine decreased by 73% in the DNX kidney; renal tissue Ang II was not altered. Approaches using cryo-treatment to ablate renal nerves may provide an adjunctive therapeutic modality in resistant renovascular hypertension.

Atherosclerotic renal artery stenosis and renal artery stenting: an evolving therapeutic option

Atherosclerotic renal artery stenosis is a common clinical problem for which the optimal therapeutic strategy remains to be defined. However, renal artery stenting procedures have significantly increased as one approach to treat this clinical problem. Despite improvements in device design and technical performance of the procedure, the benefits and results of randomized clinical trials of renal artery stenting as a therapy remain confusing. Understanding the epidemiology, pathophysiology and natural history of renal artery stenosis are central to improving the outcomes of renal artery stenting. Developing both noninvasive and invasive predictive tools to better identify which patient will respond to renal revascularization will also be beneficial. In this article, we will present an overview of atherosclerotic renal artery disease. The results of renal artery stenting will be discussed and from this, the available noninvasive and invasive tools available to assess the clinical and hemodynamic significance of renal artery stenosis will be presented.

Acute renal artery occlusion: making the case for renal artery revascularization

Atherosclerotic renal artery disease is a common disease entity that may be identified in patients with difficult-to-control hypertension and/or chronic kidney disease but is probably underdiagnosed. Current evidence from both observational and randomized studies offers mixed results regarding the support for renal artery revascularization. There is lack of equipoise with regard to the efficacy of renal artery revascularization among the interventional and renal communities, as well as disagreements on the appropriate endpoints to measure in clinical trials, which have led to selection bias confounding the scant available data. We report a patient who does not fit any clinical trial inclusion criteria with acute on chronic kidney injury and new-onset heart failure whose symptoms and renal function improved significantly after renal artery intervention.

Is There an Indication for Embolic Protection in Renal Artery Intervention?

The role of endovascular treatment of atherosclerotic renal artery disease is uncertain, particularly after the publication of the Angioplasty and Stenting for Renal Artery Lesions trial and other randomized trials. These trials have shown that nonselective treatment of patients with renal artery stenosis does not result in a benefit when compared with best medical therapy. However, all trials have identified a subgroup of patients who do respond favorably to revascularization. In particular, patients with a degree of chronic renal insufficiency, critical renal artery stenosis, and a recent decline in renal function are likely to respond positively to revascularization. Endovascular treatment of renal artery stenosis must be performed safely, particularly in the high-risk patient group with background chronic renal insufficiency. Atheroembolization occurs during renal artery revascularization, as demonstrated by ex vivo studies and the high embolic yield obtained in published series of protected renal artery revascularization. The evidence supporting embolic protection includes single-center series wherein excellent results for renal function preservation have been reported. One small, randomized, controlled trial demonstrated a significant benefit if both embolic protection and abciximab were used. There are unique demands on an embolic protection device in the renal artery circulation and a dedicated device has not been developed. Both distal filters and occlusion balloons have been successfully used. Both devices can normally be primarily passed through the stenosis, allowing the remainder of the procedure to be protected. Filters have the advantage of maintaining renal perfusion throughout the procedure. Distal occlusion balloons can capture embolic particles of all sizes although the clinical advantage is uncertain.

Revascularization versus medical therapy for renal-artery stenosis. The ASTRAL Investigators. The New England Journal of Medicine 2009; 361: 1953—1962

Study objective: The objective of ASTRAL was to determine whether percutaneous revascularization combined with medical therapy compared to medical therapy alone improves renal function and other outcomes, such as blood pressure, time to first renal event, time to first major cardiovascular event, and mortality. Study population: ASTRAL enrolled 806 patients with atherosclerotic renovascular disease from 57 centers. Patients were screened if treating clinicians felt they had clinical features suggestive of underlying atherosclerotic renovascular disease (i.e. hypertension refractory to medical therapy, or renal impairment as suggested by laboratory measurements). All patients had to have an imaging modality (i.e. computed tomographic angiography (CTA), magnetic resonance angiography (MRA) or renal artery ultrasound). This imaging had to convey that the patient had ‘substantial’ anatomical atherosclerotic stenosis in at least one renal artery that was suitable for endovascular therapy. Also, the treating clinician had to be ‘uncertain’ that the patient would benefit from revascularization. Fifty-nine percent of patients were reported to have renal artery stenosis of &gt; 70%, and 60% had a serum creatinine of ≥ 150 mmol per liter. Design and methods: ASTRAL was a randomized, unblinded study of patients with atherosclerotic renal artery disease who were assigned to percutaneous revascularization plus best medical therapy or best medical therapy alone. The primary outcome of the ASTRAL trial was the change of renal function over time, as determined by the mean slope of the reciprocal of serum creatinine. Secondary outcomes included blood pressure, time to first renal event (defined as: new onset of kidney injury, dialysis, renal transplantation, nephrectomy, or death from renal failure), time to first major cardiovascular event (defined as: myocardial infarction, stroke, death from cardiovascular cause, hospitalization for angina, fluid overload or congestive heart failure, coronary artery revascularization, or another peripheral arterial procedure), and all-cause mortality. Randomization was 1:1 via computer algorithm and was stratified by serum creatinine, glomerular filtration rate (GFR), severity of renal artery stenosis, kidney length on ultrasound, and rate of progression of renal impairment. Patients who were assigned to the revascularization plus medical therapy arm underwent percutaneous revascularization within 4 weeks. The procedure type (angioplasty alone or with stenting), was left to the discretion of the local operator. Distal protection devices were not used. Medical therapy in both arms consisted of antihypertensive drugs, statins, and antiplatelet agents. The trial was powered to detect a 20% reduction in the mean slope of the reciprocal of serum creatinine. Based on low crossover rates, it was determined that at least 750 patients would have to be enrolled. Analysis was by intention to treat. Continuous variables were subject to repeated measures analysis. Time-to-event data were expressed via Kaplan Meier curves and compared via log-rank testing. Prespecified subgroup analyses included baseline serum creatinine, GFR, severity of renal artery stenosis, kidney length, and progression of renal disease. Results: Of the 806 patients included, 403 were randomized to the revascularization arm and 403 to medical therapy only. The median follow-up was 34 months. Only 337 (83%) patients randomized to revascularization underwent the procedure, whereas 24 patients (6%) randomized to the medical therapy arm underwent revascularization. The number of antihypertensive medications used was greater in the medical therapy group than in the revascularization group at the 12-month follow-up: 2.97 versus 2.77 ( p = 0.03). The mean slope of the reciprocal of the serum creatinine concentration was —0.07 × 10— 3 liters per micromole per year in the revascularization group versus —0.13 × 10—3 liters per micromole per year in the medical-therapy group (difference of 0.06 × 10 —3 liters per micromole per year) (95% confidence interval [CI], —0.002 to 0.13, p = 0.06) with a trend favoring revascularization. After 5 years of follow-up, there was a trend toward lower mean systolic blood pressure (1.6 mmHg lower, p = 0.06) in the revascularization group. However, the mean diastolic blood pressure was significantly lower in the medical therapy group at long-term follow-up (divergence of slope of mean diastolic blood pressure: 0.61 mmHg per year, p = 0.03). There was no significant difference between renal events, time to first renal event, acute kidney injury, or development of end-stage renal disease in either group. Further, there was no difference in major cardiovascular events or overall survival in either group. The periprocedural complication rate within the revascularization group was 9% (31/359 patients). Fifty-five out of 280 patients (20%) had an adverse event by 1 month post procedure. Overall, there were 31 serious complications of revascularization in 23 patients. Per protocol analysis of patients suggested that there was no significant difference in outcomes between patients who received revascularization versus medical therapy. No differences between treatment groups were identified in any of the pre-specified subgroup analyses. Conclusions: Renal artery stenting combined with medical therapy did not improve renal function compared to medical therapy alone in patients with atherosclerotic renal artery disease.