Cardiovascular Outcomes In Renal Atherosclerotic Lesions Research Articles

Attempting to define a role for renal artery stenting: Another analysis of the CORAL trial

Modrall et al 1 Modrall G.J. Zhu H. Prasad T. Moe O. Dworkin L.D. Cutlip D.E. et al. Retrieval of renal function after renal artery stenting improves event-free survival in a subgroup analysis of the cardiovascular outcomes in renal atherosclerotic lesions trial.. J Vasc Surg. 2023; 77: 1685-1692 Abstract Full Text Full Text PDF Scopus (1) Google Scholar have reanalyzed data from the CORAL trial 2 Cooper C.J. Murphy T.P. Cutlip D.E. Jamerson K. Henrich W. Reid D.M. et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2014; 370: 13-22 Crossref PubMed Scopus (666) Google Scholar to identify a role for renal artery stenting (RAS) in the subset of patients with chronic kidney disease (CKD). They demonstrated, again, that stenting does not provide a benefit compared with optimal medical therapy in terms of event-free survival, the primary end point of their analysis and the parent trial. The blood pressure response was similar between their groups, although the change in serum creatinine and the percentage of change in the estimated glomerular filtration rate (eGFR) were better in the stented group, albeit modest. A larger percentage of the stented patients had had a ≥20% increase in their eGFR (responders) vs the medical group (25.6% vs 17.1%), although the percentage of those with a ≥20% decrease in the eGFR was similar. These responders had had improved event-free, non–renal event-free, and overall survival compared with the nonresponders. However, the presence of diabetes (negative) was the only predictor of a good response. Retrieval of renal function after renal artery stenting improves event-free survival in a subgroup analysis of the Cardiovascular Outcomes in Renal Atherosclerotic Lesions trialJournal of Vascular SurgeryVol. 77Issue 6PreviewThe Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, a multicenter randomized controlled trial with 947 patients, concluded that there was no benefit of renal artery stenting (RAS) over medical therapy. However, patients with chronic kidney disease (CKD) were not analyzed separately in the CORAL trial. CKD is a risk factor for cardiovascular and renal morbidity. We hypothesized that improved renal function after RAS would be associated with increased long-term survival and a lower risk of cardiovascular and renal events in patients with CKD. Full-Text PDF

Retrieval of renal function after renal artery stenting improves event-free survival in a subgroup analysis of the Cardiovascular Outcomes in Renal Atherosclerotic Lesions trial

ObjectiveThe Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, a multicenter randomized controlled trial with 947 patients, concluded that there was no benefit of renal artery stenting (RAS) over medical therapy. However, patients with chronic kidney disease (CKD) were not analyzed separately in the CORAL trial. CKD is a risk factor for cardiovascular and renal morbidity. We hypothesized that improved renal function after RAS would be associated with increased long-term survival and a lower risk of cardiovascular and renal events in patients with CKD. MethodsThis post hoc analysis of the CORAL trial included 842 patients with CKD stages 2 to 4 at baseline who were randomized to optimal medical therapy alone (OMT; n = 432) or RAS plus OMT (RAS + OMT; n = 410). Patients were categorized as responders or nonresponders based on the change in the estimated glomerular filtration rate (eGFR) from baseline to last follow-up (median, 3.6 years; interquartile range, 2.6-4.6 years). Responders were defined by a 20% or greater increase in eGFR from baseline; all others were designated as nonresponders. Event-free survival was defined as freedom from death and multiple cardiovascular and renal complications. Event-free survival was analyzed using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazards regression analysis was used to identify independent predictors of event-free survival. ResultsThe RAS + OMT group had a higher proportion of patients with improved renal function (≥20% increase in eGFR over baseline), compared with the OMT group (25.6% vs 17.1%; P = .003). However, event-free survival was no different for the two cohorts (P = .18 by the log-rank test). Multivariable Cox proportional hazards regression analysis identified four variables that independently correlated with event-free survival for the stented cohort. Higher preoperative eGFR (hazard ratio, 0.98; 95% confidence interval [CI], 0.96-0.99; P = .002) and being a responder to stenting (hazard ratio, 0.49; 95% CI, 0.26-0.95; P = .033) increased event-free survival, whereas a history of congestive heart failure (hazard ratio, 2.52; 95% CI, 1.46-4.35; P < .001) and a higher preoperative systolic BP (hazard ratio, 1.02; 95% CI, 1.01-1.03; P = .002) decreased event-free survival. Within the stented group, 105 of 410 patients (25.6%) were responders. Event-free survival was superior for responders, compared with nonresponders (P = .009 by log-rank test). The only independent preoperative negative predictor of improved renal function after stenting was diabetes (odds ratio, 0.37; 95% CI, 0.16-0.84; P = .017), which decreased the probability of improved renal function after RAS + OMT. A subset of patients (23.4%) after RAS had worsened renal function, but OMT alone produced an equivalent incidence of worsened renal function. An increased urine albumin/creatinine ratio was an independent predictor of worsened renal function after RAS. ConclusionsCORAL participants who demonstrated improved kidney function after RAS + OMT demonstrated improved event-free survival. This finding reinforces the need for predictors of outcome to guide patient selection for RAS.

Cardiovascular Disease Prevention in Patients With Atherosclerotic Renovascular Disease-Induced Resistant Hypertension: Further Considerations for 24-Hour BloodPressure Profiles.

Cardiovascular Disease Prevention in Patients With Atherosclerotic Renovascular Disease-Induced Resistant Hypertension: Further Considerations for 24-Hour BloodPressure Profiles.

Abstract 13819: Circulating PON Lactonase Activity Predicts Major Adverse Cardiac Events in Subjects With Atherosclerotic Renal Artery Disease

Introduction: Decreased plasma lactonase activity, catalyzed by high-density lipoprotein (HDL)-associated paraoxonase (PON), is associated with increased oxidant stress and cardiovascular risk in settings such as coronary artery disease as well as some etiologies of chronic kidney disease (CKD). However, whether circulating PON lactonase activity predicts outcomes in atherosclerotic renal artery stenosis (ARAS) is unknown. We sought to determine the prognostic value of circulating PON lactonase activity in subjects with ARAS, particularly in relation to established risk factors. Methods/Results: PON lactonase activity was measured in plasma of subjects with ARAS and either systolic hypertension while taking ≥2 antihypertensive drugs or CKD (n=718) enrolled in the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study as well as a cohort of apparently healthy, normotensive non-ARAS subjects (n=33). Participants with ARAS were prospectively followed for incident major adverse cardiac events (MACE, composite of cardiovascular death, nonfatal myocardial infarction, and stroke) over a median follow-up period of 43 months (interquartile range, 31 to 55). PON lactonase activity in ARAS subjects was significantly lower compared with that in non-ARAS control subjects [mean±SD, 2466±839 vs 3514±745 pmol/min/mL, P&lt;0.001]. Next, participants were dichotomized based on the baseline plasma levels of PON lactonase activity, into high (&gt; median) or low (≤ median) groups and were used to predict incident MACE at 3 years. Participants with lower PON lactonase activity had increased MACE at 3 years [67/359 (17%) vs 44/359 (12%), p&lt;0.05]. Lower circulating PON lactonase activity (hazard ratio 1.26, 95% CI 1.0 to 1.53, p=0.016) was a predictor of MACE. After adjusting for traditional risk factors and medication use, lower PON lactonase activity (hazard ratio 1.22, 95% CI 1.01 to 1.50, p=0.04) still conferred an increased risk of MACE. Conclusions: In patients with ARAS, decreased circulating PON lactonase activity, a measure of diminished antioxidant properties of HDL, predicts higher risk of incident long-term adverse cardiovascular events in multivariate models adjusting for established clinical and biochemical risk factors.

Clinical predictors of blood pressure response after renal artery stenting

ObjectiveThe Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, a multicenter randomized controlled trial, failed to demonstrate a benefit of renal artery stenting (RAS) over medical therapy in patients with renal artery stenosis and hypertension. However, there are patients for whom RAS is a consideration because of failure of medical therapy. Unfortunately, selection of patients for RAS is complicated by a lack of validated predictors of blood pressure (BP) response. A previous single-center study identified three preoperative markers of BP response to RAS: requirement for four or more antihypertensive medications, preoperative diastolic BP >90 mm Hg, and preoperative clonidine use. To date, these markers of outcome have not been independently validated. The aim of this study was to validate these markers using data from the CORAL trial. MethodsAll patients randomized in the CORAL trial to RAS were included. American Heart Association guidelines were used to categorize patients as BP responders or nonresponders to RAS. BP responders were defined by a postoperative BP <160/90 mm Hg with a reduced number of antihypertensive medications or a reduction in diastolic BP to <90 mm Hg with the same medications after RAS. Patients with stable or worsened BP were labeled nonresponders. Variables associated with a favorable BP response were identified by multivariable logistic regression analysis. ResultsThere were 436 patients who underwent RAS with a median age of 70 years (interquartile range [IQR], 63-76 years). The median systolic and diastolic BPs of the stented cohort at baseline were 149 mm Hg (IQR, 132-164 mm Hg) and 78 mm Hg (IQR, 70-87 mm Hg), respectively. A positive BP response occurred in 284 of 436 (65.1%) stented patients. Multivariable logistic regression analysis identified three independent markers of a positive BP response: requirement for four or more medications (odds ratio, 5.9; P < .001), preoperative diastolic BP >90 mm Hg (odds ratio 13.9; P < .001), and preoperative clonidine use (odds ratio, 4.52; P = .008). The percentage of patients with a positive BP response increased incrementally as the number of markers per patient increased, based on the Cochran-Armitage test for trend (P < .0001). ConclusionsIn patients from the CORAL trial who underwent RAS, the previously reported clinical markers of BP response were validated. A prospective trial to validate their utility as predictors of BP response to RAS is warranted.

Prediction of cardiovascular outcomes with machine learning techniques: application to the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study.

BackgroundData derived from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study were analyzed in an effort to employ machine learning methods to predict the composite endpoint described in the original study.MethodsWe identified 573 CORAL subjects with complete baseline data and the presence or absence of a composite endpoint for the study. These data were subjected to several models including a generalized linear (logistic-linear) model, support vector machine, decision tree, feed-forward neural network, and random forest, in an effort to attempt to predict the composite endpoint. The subjects were arbitrarily divided into training and testing subsets according to an 80%:20% distribution with various seeds. Prediction models were optimized within the CARET package of R.ResultsThe best performance of the different machine learning techniques was that of the random forest method which yielded a receiver operator curve (ROC) area of 68.1%±4.2% (mean ± SD) on the testing subset with ten different seed values used to separate training and testing subsets. The four most important variables in the random forest method were SBP, serum creatinine, glycosylated hemoglobin, and DBP. Each of these variables was also important in at least some of the other methods. The treatment assignment group was not consistently an important determinant in any of the models.ConclusionPrediction of a composite cardiovascular outcome was difficult in the CORAL population, even when employing machine learning methods. Assignment to either the stenting or best medical therapy group did not serve as an important predictor of composite outcome.Clinical Trial RegistrationClinicalTrials.gov, NCT00081731

Renal Artery Stenosis: New Findings from the CORAL Trial.

The goal of this review is to summarize recent advances in the field and highlight important new insights from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial regarding the optimal management of patients with renal artery stenosis (RAS). The CORAL trial demonstrated that subjects with RAS had similar outcomes whether randomized to optimal medical therapy alone or optimal medical therapy plus renal artery stenting. Subgroup analyses have failed to demonstrate that baseline blood pressure or lesion gradients can predict which subjects may have improved response after stent intervention. Importantly, urine albumin to creatinine ratio appears to different subjects that may benefit from stent intervention versus subjects that are unlikely to achieve any benefit. In addition, there was a trend toward increase benefit in subjects with greater percent stenosis. Atherosclerotic RAS is a frequent finding and is often seen in patients with resistant hypertension, congestive heart failure, chronic kidney disease, and rarely those who need renal replacement therapy. Risk factors for RAS overlap with those of generalized atherosclerosis including hyperlipidemia, smoking, hypertension, and diabetes. Patients with CAD or PVD frequently have co-existing RAS. The management of RAS has been controversial for many years. The CORAL trial provides important insights into the optimal management of subjects with RAS.

Renal Salvage with Renal Artery Stenting Improves Long-term Survival

The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) Trial castdoubt on the benefits of renal artery stenting (RAS). However, the outcomes for patients with chronic kidney disease (CKD) were not analyzed separately in the CORAL Trial. We hypothesized that patients who experienced a significant improvement in renal function after RAS would have improved long-term survival, compared with patients whose renal function was not improved by stenting. This single-center retrospective study included 60 patients with stage 3 or worse CKD and renal artery occlusive disease who were treated with RAS for renal salvage. Patients were categorized as "responders" or "nonresponders" based on postoperative changes in estimated glomerular filtration rate (eGFR) after RAS. "Responders" were those patients with an improvement of at least 20% in eGFR over baseline; all others were categorized as "nonresponders." Survival was analyzed using the Kaplan-Meier method. Cox proportional hazards regression was used to identify predictors of long-term survival. The median age of the cohort was 66years (interquartile range [IQR], 60-73). Median preoperative eGFR was 34mL/min/1.73m2 (IQR, 24-45). At late follow-up (median 35months, IQR, 22-97months), 16 of 60 patients (26.7%) were categorized as "responders" with a median increase in postoperative eGFR of 40% (IQR, 21-67). Long-term survival was superior for responders, compared with nonresponders (P=0.046 by log-rank test). Cox proportional hazards regression identified improved renal function after RAS as the only significant predictor of increased long-term survival (hazard ratio=0.235, 95% confidence interval = 0.075-0.733; P=0.0126 for improved versus worsened renal function after RAS). Successful salvage of renal function by RAS is associated with improved long-term survival. These data provide an important counter argument to the prior negative clinical trials that found no benefit to RAS.

BR 05-2 ANGIOPLASTY OF ATHEROSCLEROTIC RENAL ARTERY STENOSIS

Abstract Atherosclerotic renal artery stenosis is an increasingly recognized medical problem especially in elderly patients. It commonly occurs with systemic manifestations including hypertension (HTN), chronic kidney disease (CKD) or atherosclerotic diseases including coronary or peripheral artery disease. Significant renal artery stenosis may result in HTN, ischemic nephropathy, however it is still in debate about the benefit of revascularization. Although several randomized controlled trials including Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) and Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study has failed to reveal a significant benefit of angioplasty, angioplasty with medical therapy is increasingly accepted in some patients with certain clinical conditions.For determining appropriate candidates for renal artery angioplasty, anatomical evaluation of renal artery stenosis and atherosclerotic change of abdominal aorta should be preferentially undergone. Angiographic stenosis more than 50% with physiologic significance, or ≥70% stenosis is considered significant. Translesional pressure gradient with or without hyperemia should be routinely assessed in intermediate stenosis (50-70%). Intravascular ultrasound assessment may be used to evaluate luminologic severity or characteristics.Global renal ischemia caused by renal artery stenosis should be an appropriate indication of revascularization, however unilateral and solitary ischemia would be considerable. Patients with cardiac disturbance syndrome or pulmonary edema relevant to renal artery stenosis can be managed with renal artery angioplasty. Several prospective randomized trials have failed to show a significant difference in blood pressure (BP) response after revascularization or medical treatment, nevertheless resistant HTN with global renal ischemia would be a proper indication of revascularization. Both patient groups with revascularization and medication alone in CORAL showed similar BP response about 15 mmHg. Such BP responders with optimal medication may be not appropriate candidates for revascularization for controlling BP. Patients with reduced renal function and global renal ischemia may be also good candidates for renal artery stenting. However, evidences to support revascularization in unilateral renal artery stenosis are limited. Revascularization would be considered if renal artery stenosis is relevant to hemodynamic significance. Although revascularization with stenting have been commonly used for patients with renal artery stenosis, previous results are inconclusive and lacking to support comprehensive indications of current clinical application. Selection of candidates who benefits with angioplasty should be carefully conducted with sufficient diagnostic evaluation.

Endovascular Treatment of Renal Artery Stenosis in the Post CORAL Era.

Atherosclerotic renal artery stenosis (RAS) is highly associated with hypertension and renal insufficiency. Determining causation and who may benefit from RAS treatment remains difficult. The role of endovascular management of atherosclerotic RAS was challenged by several recent randomized controlled trials (RCT) which failed to demonstrate benefit of stenting. In the largest RCT to date, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study did not find benefit of revascularization compared to medical therapy alone. While such RCTs represent the highest level of evidence to date, the conclusions drawn from them should be interpreted with caution due to substantial flaws in study design, inclusion, and exclusion criteria. The current AHA/ACC recommendations for RAS management are supported by many level-II evidence cohort studies which consistently found benefit of revascularization in groups with the highest likelihood of clinically significant RAS. Further study of these patient groups are needed to define a clear role for endovascular therapy of renal artery stenosis.

Renal Artery Stent Outcomes: Effect of Baseline Blood Pressure, Stenosis Severity, and Translesion Pressure Gradient

BackgroundMultiple 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. ObjectivesThe study sought to test the hypothesis that pressure gradients, stenosis severity, and/or baseline blood pressure affects outcomes after renal artery stent placement. MethodsUsing 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. ResultsThere were no statistically significant differences in outcomes based on the examined variables nor were there any consistent nonsignificant trends. ConclusionsBased 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)

Abstract 17358: Stenting of Atherosclerotic Renal Artery Stenosis Does Not Prevent Congestive Heart Failure, an Analysis of the Coral Trial

Introduction: In current guidelines congestive heart failure (CHF) is an indication for renal artery stenting, however there is no data on the utility of stenting for the prevention of CHF. We sought to determine the effect of renal artery stenting in patients with atherosclerotic renal artery stenosis (ARAS) without a history of CHF. Hypothesis: In ARAS renal artery stenting does not prevent incident CHF in patients with no history of CHF. Design and method: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial is a prospective, international, multicenter clinical trial that randomized participants with ARAS, who received optimal medical therapy plus stenting versus no stenting. Optimal medical therapy included treating blood pressure and diabetes to goal, use of an angiotensin receptor-blocking drug, statin, and anti-platelet therapy. Glomerular filtration (eGFR) was estimated using the MDRD-GFR equation. Patients were followed for a median of 43 months (IQR, 31 to 55). Results: At enrollment, there were 795 out of 931 patients without a history of CHF, 395 were in the medical therapy group and 400 were in the medical therapy plus stenting group. In this group 117/795 had global renal ischemia. The rate of CHF admission (7% vs. 6%. p=0.74) and the pulmonary edema rate within those admitted for CHF were not different (82% vs. 64%, p=0.21). The rate of incident CHF was not different in patients with global renal ischemia and renal stenting did not prevent CHF events in this subgroup. Neither the composite event rate (35% vs. 34%, p=0.72), nor the rate of cardiovascular death (8% vs. 8%, p=0.96) differed between the two groups. At 3-year follow-up no differences were observed between medical therapy and medical therapy plus stenting for systolic blood pressure (SBP) (135±19 vs. 134±21 mmHg, p=0.74) or eGFR (56±22 vs. 55±23 ml/min, p=0.50). Conclusions: Renal artery stenting and optimal medical therapy, when compared to optimal medical therapy only, did not reduce the risk of CHF, or other cardio-renal events in patients that were enrolled without history of CHF in the CORAL trial.

Regional and physician specialty–associated variations in the medical management of atherosclerotic renal–artery stenosis

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.

CORAL: Similar Outcomes with Intervention, Medical Therapy in Renal Stenosis

Revascularization with stenting added to optimal medical therapy did not prevent clinical events in patients with atherosclerotic renal artery stenosis in the prospective, randomized, open-label, international, multicenter Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study. This article details the results.

Abstract 18388: Albuminuria Determines Event-Free Survival in Atherosclerotic Renal-Artery Stenosis

Introduction: Stenosis severity and revascularization may have little relation to outcomes in patients with atherosclerotic renal artery stenosis (ARAS). Albuminuria is a direct indicator of glomerular injury and kidney health. The effect of albuminuria on survival in people with ARAS is not well characterized. Hypothesis: Proteinuria predicts clinical events in people with ARAS. Methods: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) clinical trial is a prospective trial of individuals with ARAS. Patients were followed to a maximum of 8 years. Urine albumin and creatinine were measured at a single core lab and the ratio was log transformed (LUACR). The composite endpoint included: cardiovascular (CV) or renal mortality, myocardial infarction (MI), stroke, chronic heart failure (CHF), progressive renal insufficiency (PRI), and renal replacement therapy (RRT). Utilizing receiver operating characteristic (ROC) curves, we developed 3 cutoff points for the LUACR using three methods: Youden’s, closest to the top-left point and the sample median. In order to verify the cutoff point we randomly divided the sample into a training set and a verification set of equal size. Cross verification was applied and the simulation was repeated 5000 times. The analyses are controlled by age, gender, cystatin-c, and systolic blood pressure. Results: Cross verification shows that Youden’s method gives the highest specificity and accuracy. It yields an optimal cutoff point of LUACR=3.83 (UACR is exp(3.83)=46.06). Subjects with values above this threshold, in the verification sample, had higher rates of the composite event rate (50% vs. 27%), PRI (27% vs. 13%), and CHF (16% vs. 5%), all p&lt;0.001; CV death (13% vs. 7%), and all-cause mortality (14% vs. 7%), both p&lt;0.01. Conclusions: Albuminuria powerfully predicts adverse cardiovascular and renal events, including all-cause mortality, in people with ARAS.

Abstract 20258: Stenosis Severity and Kidney Function in Atherosclerotic Renal Artery Stenosis

Introduction: Ischemic nephropathy due to atherosclerotic renal artery stenosis (ARAS) is associated with poor event free survival. However, previous studies suggest that stenosis severity has a poor relation to kidney function. We sought to test the interactions of stenosis severity, and revascularization, on kidney function in people with ARAS. Hypothesis: Stenosis severity is associated with poor renal function in people with ARAS. Methods: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) clinical trial is a prospective trial of individuals with atherosclerotic renal-artery stenosis. Patients were followed to a maximum of 8 years. Angiographic images were measured at a single core lab (University of Virginia) using quantitative computer-assisted angiography. Estimated glomerular filtration rate (eGFR) was measured using creatinine and cystatin-C, performed at a single core lab (University of Minnesota), and calculated using the CKD-EPI Creatinine-Cystatin C formula. The analyses are controlled by age and gender. Results: At baseline CKD-EPI eGFR was strongly and negatively correlated with percent stenosis (-0.2472, p&lt;0.0001) and positively correlated with minimal luminal diameter (0.2974, p&lt;0.0001). Interestingly, peak systolic pressure gradient and mean pressure gradients were not (p=ns for both). At three years follow-up baseline percent stenosis remained significant by univariate analysis (0.1380, p=0.01), however, it was not significant by multivariate analysis. Conclusions: Stenosis severity is strongly related to kidney function at the time of presentation in patients with atherosclerotic renal artery stenosis. However, by three years follow-up, this relationship appears to be lost.

Angioplastie rénale : état des lieux en 2014

Atherosclerotic renal artery stenosis can cause ischaemic nephropathy and arterial hypertension. Renal artery stenosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Many patients with RAS may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the cardiovascular outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of RAS for cardiologists in the context of recent randomized clinical trials. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary edema, rapidly declining renal function and severe resistant hypertension.

Renal artery stenting in patients with uncontrolled hypertension: should we? And to whom?

In this issue of the Journal, Chrysant and colleagues evaluated the longer-term efficacy of renal artery stenting with respect to blood pressure (BP) control by analyzing the results of the Safety and Effectiveness Study of the Herculink Elite Renal Stent to Treat Renal Artery Stenosis (HERCULES) trial after 36 months of follow-up. 1 The HERCULES trial was a multicenter, single-arm trial of 202 patients with uncontrolled hypertension caused by atherosclerotic renovascular disease (ARVD) treated by percutaneous renal artery dilatation and renal stent placement. In the original HERCULES trial, the authors found that the absolute reduction in systolic BP (SBP) after 9 months was related to the severity of the baseline hypertension before intervention. In ARVD patients with preprocedure SBP >180 mm Hg and a postprocedure reduction in SBP, the mean reduction recorded at 9 months was 48 mm Hg, while patients with ARVD with a baseline SBP between 140 mm Hg and 160 mm Hg had a decrease of only 23 mm Hg in SBP at 9 months. In addition, this trial demonstrated excellent procedurerelated safety, with a 30-day composite safety endpoint rate of 1.5%. 2 Chrysant and colleagues further hypothesized that if the renal stent used in the initial HERCULES trial maintained renal artery patency over time, then the clinical benefit confirmed in the initial trial should be sustained over time. Based on this hypothesis, the

Stenting for atherosclerotic renal-artery stenosis: A blind alley?

Renal-artery stenosis, a common disease among persons older than 65 years,may result in hypertension, ischemic nephropathy, and multiple long-term complications [1]. Early studies [2] suggested that renal-artery angioplasty or stentingmay result in significant reductions in systolic blood pressure. However, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial [3] recently presented a definitive test of the usefulness of renal-artery stents for moderately severe renalartery stenosis and made a conclusion that renal-artery stenting is no better than medical therapy alone in preventing clinical events. It seems that stenting for renal-artery stenosis after years of its clinical use hits a blind alley. However, pathophysiological changes after stenting include not only improvement in the diameter of the stenotic renal artery but also the tissues of and around the artery, particularly the sympathetic nerve fibers which lie in the adventitia of the renal artery (Fig.1). A recent research [4] demonstrated that balloon angioplasty can reduce the number of sympathetic nerve fibers of the renal artery. So this may be more than just a theoretical consideration. Renal-artery stenosis is characterized not onlybyactivationof the renin–angiotensin system, but also byheightened sympathetic drive [5] which contributes to the pathophysiology of numerous chronic cardiovascular diseases such as essential hypertension, heart failure, chronic kidney disease, diabetes and so on. Nowadays percutaneous catheter-based renal denervation (RDN) is emerging as a new, effective and safe approach to achieve sustained blood pressure reduction in patients with resistant hypertension which can decrease sympathetic activity by interrupting the afferent and efferent renal sympathetic nervous fibers located in the adventitia of the renal arteries by delivery of radiofrequency energy. Herein, we hypothesize that RDN on patients with prior renal stents may enhance the damages of renal sympathetic nervous fibers and reduce the sympathetic activities to a much lower level. However, renal-artery stenosis and prior renal stents are considered a contraindication in routine clinical practice of RDN due to technological unavailability and a worry of deterioration of stenosis. Nevertheless, one case report [6] explored and demonstrated the feasibility and potential effectiveness of the combination of RDN and renal stenting. What's more, a recent small animal study [7] proved that vascular brachytherapy which has been approved for the treatment of in-stent restenosis can also cause renal sympathetic nerve fibrosis while avoiding significant damage to the renal artery. All theseexplorationsmaybreak new ground of therapy with renal-artery stenosis.

Management of atherosclerotic renovascular disease after Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL).

Many patients with occlusive atherosclerotic renovascular disease (ARVD) may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial and the Stent Placement and Blood Pressure and Lipid-Lowering for the Prevention of Progression of Renal Dysfunction Caused by Atherosclerotic Ostial Stenosis of the Renal Artery (STAR) and ASTRAL. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Although hemodynamically significant, ARVD can reduce renal blood flow and glomerular filtration rate; adaptive mechanisms preserve both cortical and medullary oxygenation over a wide range of vascular occlusion. Progression of ARVD to severe vascular compromise eventually produces cortical hypoxia, however, associated with active inflammatory cytokine release and cellular infiltration of the renal parenchyma. In such cases ARVD produces a loss of glomerular filtration rate that no longer is reversible simply by restoring vessel patency with technically successful renal revascularization. Each of these trials reported adverse renal functional outcomes ranging between 16 and 22% over periods of 2-5 years of follow-up. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of ARVD for clinical nephrologists in the context of recent randomized clinical trials and experimental research.