A Case of Drug‐Resistant Renovascular Hypertension due to Renal Artery Stenosis Successfully Treated by Nephrectomy of the Affected Kidney

The case favoring renal artery stenting for individuals with renal artery hypertension is largely circumstantial. At best, the clinical evidence presented in this discussion is derived primarily from nonrandomized cohort studies. It would certainly be easier to argue that medical therapy is preferred for such individuals because there are 3 published randomized clinical trials that concluded just that and none that support renal artery intervention. Nonetheless, there is considerable evidence to support the role for revascularization in general, and stenting specifically, as an important adjunctive therapy to medical therapy in the care of patients with renal artery stenosis (RAS). The argument has 3 principal components: observations about the impact on cardiovascular physiology, end-organ effects, and natural history. Response by Dworkin and Jamerson p 270 RAS is associated with and is an important cause of secondary hypertension. RAS causes endocrine activation with release of renin from renal juxtaglomerular cells. Renin catalyzes the breakdown of angiotensinogen to angiotensin I. Angiotensin I is transformed by angiotensin-converting enzyme into angiotensin II, and angiotensin II promotes the release of aldosterone from the adrenal cortex.1 Angiotensin II is a potent vasoconstrictor,2 substantially more potent than epinephrine, and is implicated in end-organ damage in the heart3 and kidney.4 RAS is suggested to cause 2 types of hypertension. With unilateral RAS and a normally perfused and normally functioning contralateral kidney, blood pressure elevation is referred to as “renin dependent” and is characterized by increased peripheral resistance.5,6 In this circumstance, renin and angiotensin levels remain elevated, but volume expansion is limited by natriuresis of the contralateral normally functioning kidney.6 Importantly, although renin levels are elevated, the value of peripheral or even renal vein renin values is limited by substantial overlap with patients having essential hypertension.7,8 When stenoses are bilateral or when the …

Atherosclerotic renal artery stenosis (RAS) is more common than has been previously appreciated1,2 and is an independent predictor of death regardless of the presence, severity, or method of revascularization of coronary artery disease.3–5 Among 1235 patients undergoing diagnostic coronary angiography, multivariate analysis demonstrated that RAS (>50%) was a stronger independent predictor of all-cause mortality (relative risk [RR], 2.9; 95% confidence interval [CI], 1.7 to 7.0) than congestive heart failure (RR, 2.3; 95% CI, 1.3 to 4.1), elevated left ventricular ejection fraction (RR, 1.7; 95% CI, 1.2 to 2.2), or decreased renal function (serum creatinine) (RR, 1.3; 95% CI, 1.1 to 1.5).3 A subsequent expansion of that study group, extended to 3987 patients undergoing abdominal aortography at the time of diagnostic cardiac catheterization, identified an incremental effect of the severity of RAS on the 4-year mortality rates. They found that a mild-to-moderate (50%) RAS was associated with a 30% 4-year mortality rate, which almost doubled (52%) with severe (>95%) RAS.4 The cause-and-effect relation between RAS and death is uncertain. It is possible that the presence of RAS is simply a marker for more diffuse or extensive atherosclerosis, which would result in more vascular-related deaths. However, there is one study5 that raises the possibility that the treatment of RAS with a renal stent in patients with renal insufficiency can improve mortality rates. In this trial, patients who improved their renal function after renal stent placement had significantly better survival rates compared with those whose renal function did not improve. A dedicated educational effort aimed at improving the diagnosis and treatment of peripheral arterial disease, including RAS, has been supported over the past 10 years by several professional societies.6–8 There is now objective evidence from the Medicare database that this effort to increase the number of patients …

The primary goal of this American Heart Association renal intervention writing group was to discuss current controversies related to renal interventions and to recommend important areas of clinical research and advocacy initiatives in this peripheral arterial bed. The 4 areas covered in this section include (1) management of asymptomatic renal artery disease, (2) treatment of ischemic nephropathy, (3) prevention and treatment of atheroembolism in renal artery interventions, and (4) treatment of renal in-stent restenosis (ISR). Atherosclerotic renal artery disease is an often unrecognized contributor to refractory hypertension, renal insufficiency, and increased risk of cardiovascular death.1,2 Renal artery disease is associated with increased cardiovascular events (myocardial infarction, stroke, and death), and when associated with symptomatic coronary artery disease, it independently doubles the risk of death.3 Additionally, the presence of bilateral renal artery stenoses is associated with a reduced 4-year survival rate when compared with unilateral disease (47% versus 59%, P <0.001).3 Hypertension, renal insufficiency, and multisystem atherosclerosis are common entities, and the independent occurrence of these conditions is frequent. Thus, the physician must distinguish between association and causation in the evaluation of patients with atherosclerotic renal artery disease and critically appraise the potential for clinical improvement in selecting patients for renal artery intervention. In contrast to other regional manifestations of atherosclerosis, it is impractical to classify patients with atherosclerotic renal artery disease into symptomatic or asymptomatic categories. Two of the cardinal manifestations of renal artery disease, hypertension and renal insufficiency, are frequently “silent” with regard to clinical manifestations until end-organ damage or uremia occurs. Thus, the majority of patients may be deemed asymptomatic. A more appropriate classification of patients with atherosclerotic renal artery disease may be to classify them in relation to potential clinical consequences. We propose the following classification scheme in patients with renal artery disease:

Background: In this article, the author discusses critical appraisals of the major randomized controlled trials on the management of Atherosclerotic Renovascular Disease (ARVD). The article will also discuss the limitations of the published trials, while highlighting the crucial aspect of appropriate patient selection, the serious flaws noted, and the quality of the main studies. Also included are the six major randomized controlled trials that compared the difference between revascularization, either surgical or PTRA (Percutaneous Renal Angioplasty), with or without stent versus conservative management (medication).The author also discusses the recommended research for the management of atherosclerotic renovascular disease. Methodology and search strategies to identify studies: A comprehensive search of PUBMED including Medical Subject Headings (MeSH) data base from 1990 to may 2012 and The Cochrane library was completed. Searching was only for relevant English papers related to the management of Atherosclerotic renovascular disease.. CASP questionnaire, Jadad scaling and (Oxford Centre for Evidence-based Medicine) levelling of evidence are used for the purpose of the critical appraisal. Criteria for considering studies for this article: To be considered, clinical studies had to be randomized trials comparing intervention; balloon angioplasty or stenting or both or surgical revascularization versus medical treatment, or surgical versus balloon angioplasty with or without stenting in hypertensive patients who had atherosclerotic renal artery stenosis with a minimum of three months of follow up after treatment Only those studies included with adult patients (age >18 years) who had uncontrolled hypertension (diastolic blood pressure ≥ 95mmHg, treated or untreated) and moderate-to-severe (≥50%) unilateral or bilateral atherosclerotic renal artery stenosis. Studies which were not randomized or those related to fibromuscular dysplasia, meta-analysis, and diagnostic studies were excluded. Objectives: Explaining a critical appraisal of six major randomized clinical trials which compared Revascularization (intervention) to medication (conservative treatment) which includes Angioplasty and Stenting for Renal Artery Lesions Trial (ASTRAL), Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function Trial (STAR), Dutch Renal Artery Stenosis Intervention Cooperative (DRASTIC), Essai Multicentrique Medicaments vs. Angioplastie trial (EMMA), Scottish and Newcastle Renal Artery Stenosis Collaborative Group trial (SNRASCG), and Prospective randomized trial of operative vs. interventional treatment for renal artery ostial occlusive disease (RAOOD) trials. We also highlighted some points about the ongoing CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) trial. Conclusions: Correction of Astherosclerotic Renal Artery Stenosis (ARAS), either by surgical revascularization or percutaneous methods, including stenting, has not been shown to be beneficial in treating Atherosclerotic RAS over conservative treatment, although some of the studies showed blood pressure control benefit in intervention groups like EMMA, SNRASCG and post hoc analysis of DRASTIC studies. Consequently, it seems reasonable to consider interventional procedures to correct Renal artery stenosis in patients who do not respond to medical therapy or with poorly-controlled or resistant hypertension; recurrent flash pulmonary edema; dialysis dependent renal failure resulting from atherosclerotic renal artery stenosis; chronic kidney disease and bilateral renal artery stenosis; or Renal artery stenosis to a solitary functioning kidney and waiting for the next available research with less flaws and biases.

Circadian blood pressure (BP) variation were studied in patients with renovascular hypertension (RVH) and primary aldosteronism (PA). Ambulatory BP (ABP) was monitored every 5 min for 24 hrs in a ward setting in 23 patients with PA and 17 patients with RVH (13 patients with unilateral renal arterial stenosis and 4 with bilateral stenosis). In patients with RVH, ABP was monitored before and after treatment with a converting enzyme inhibitor or percutaneous transluminal angioplasty. Plasma renin activity (PRA) was high before percutaneous transluminal angioplasty in almost all patients with RVH and low in those with PA. Ordinary circadian BP variation, i.e. nocturnal fall and diurnal rise in BP, was confirmed in the patients with unilateral or bilateral renal artery stenosis. Percutaneous transluminal angioplasty successfully normalized both BP and PRA in those with RVH. Normal circadian BP variation was observed in those with RVH before the treatment with a converting enzyme inhibitor or percutaneous transluminal angioplasty as well as during treatment with the former and after treatment with the latter. Circadian BP variation in the patients with RVH was affected by the pathogenesis of renal artery stenosis alone, i.e, fibromuscular hyperplasia and atherosclerosis; with fibromuscular hyperplasia normal circadian BP variation was observed, while with atherosclerosis, nocturnal BP fall was restricted or eliminated. Circadian BP variation in those with PA before and after excision of adrenal adenoma was essentially similar to that in normal subjects and essential hypertensive patients. From these it seems that in patients with RVH or PA, circadian BP variation is not affected by hypertension per se or by pathogenesis of hypertension.

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

Renal angioplasty for treatment of hypertensive patients with fibromuscular dysplasia. No country for old men

Percutaneous revascularization for ischemic nephropathy: the past, present, and future

Medium-term Results of Renal Artery Revascularization in the Post-astral Era

Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy

Treatment of Renovascular Hypertension with Percutaneous Transluminal Angioplasty: Experience in Spain

Date written: December 2008Final submission: October 2009

Symptomatic renal artery stenosis (RAS) is mainly treated with pharmacological blood pressure control, sometimes with percutaneous transluminal renal angioplasty (PTRA). It is unclear if PTRA benefits these patients over time. To determine long-term renal function, morbidity, and mortality in patients with symptomatic RAS treated with PTRA, and whether long-term outcomes are associated with angiographic restenosis. Retrospective single-center, long-term follow-up of 57 patients with atherosclerotic RAS treated with PTRA with stent during 1995-2004 and investigated for restenosis with angiography after one year. Outcomes were retrieved from medical records and from mandatory healthcare registries. Mortality rates were related to expected survival in an age- and gender-matched population, using a life-table database. Surviving patients were assessed with blood pressures, laboratory tests, duplex ultrasonography, and radioisotope renography. Median follow-up was 11 years 7 months. Major indications for PTRA were therapy-resistant hypertension and declining renal function. Angiographic restenosis at one year was found in 21 of 57 patients (37%). Thirty-six patients (60%) died during follow-up. Main cause of death was cardiovascular events (54%). Mortality was significantly increased, and morbidity and healthcare utilization were high. Hypertension control during follow-up was stable with persistent need for anti-hypertensive medication, and renal function remained moderately reduced with no long-term difference between patients with vs. without restenosis. Long-term prognosis after PTRA for atherosclerotic RAS is dismal, with high mortality and morbidity and reduced renal function, despite maintained hypertension control. Restenosis does not appear to affect late outcome.

Objective To explore the short term efficacy and safety of percutaneous transluminal renal artery stenting in patient with renal artery stenosis.Methods From January 2003 through June 2012,fifty hypertension patients with unilateral or bilateral renal artery stenosis ≥70％ were successfully treated by percutaneous translumminal renal angioplasty with stent (PTRAS).There were 32 males and 18 females with an average age of (51.2 ± 12.3) years ranged from 21 ～78 years.The blood pressure level,dosage of anti-hypertension drugs and serum creatinine (Scr) of patients were documented and analyzed before and after stenting.All patients were clinically followed up for 6 months after stenting.Continuous variables were analyzed by using t-test for comparison among patients.Results The technical success rate was 100％.Of them,16 patients were cured,30 patients improved and 4 patients ineffective.There were significant differences in blood pressure,sCr and dosage of anti-hypertension drugs between post-stenting and prestenting [SBP (145.7 ±11.3) vs.(179.1 ±22.3) mmHg; DBP [(75.1±9.2) vs.(112.5 ±19.2)mmHg],sCr [(138.2 ±20.3) vs.(191.1 ±36.5) μmol/L] (P＜0.01) and the dosage of antihypertension drug was dramatically decreased.And there were no adverse events found during follow-up period.Conclusions The success rate of PTRAS technique was high,and the blood pressure of patients could be effectively controlled by it,being beneficial to renal function. Key words: Hypertension; Renal artery stenosis; Renal angioplasty with stent

Introduction Whilst renal involvement in Alagille syndrome is common, its manifestation is varied, and bilateral renal artery stenosis is relatively rare. Patients with Alagille syndrome are at increased risk of bleeding and this must be taken into account when planning invasive procedures such as percutaneous transluminal angioplasty (PTA). We reviewed four cases of children with Alagille syndrome and renal artery stenosis who were referred to the renovascular service at a large tertiary paediatric nephrology centre for management of hypertension. We aimed to determine whether PTA was safe and effective for the treatment of renovascular hypertension in such patients. Methods A retrospective search was conducted of a local database of all patients with confirmed Alagille syndrome and renovascular hypertension treated with PTA. Data for each patient was then collected from medical and electronic records. Results Four patients were identified with Alagille syndrome and renovascular hypertension. In total, 8 PTA procedures were carried out including one for management of renal artery aneurysm. There were no intra or peri-operative complications including significant bleeding. In addition, two patients needed unilateral nephrectomies for non-functioning kidneys. 75% of patients had improvement in blood pressure at last follow up. There was a peri-procedural rise in serum creatinine of 10–73% in 57% of PTA procedures, the majority of which normalised at last follow up. Conclusions In a tertiary paediatric renovascular centre, PTA can be safely performed in patients with Alagille syndrome. Improvement in blood pressure was observed in 75% of cases. Furthermore, this study confirms that patients with Alagille syndrome and renovascular hypertension might need more than one PTA and these should be done in a specialist centre with experience in this patient cohort.