A Case of Surgical Revascularization in a Patient with Uncontrolled Renovascular Hypertension and Renal Dysfunction after Repeated Percutaneous Transluminal Renal Angioplasty (PTRA) for More Than 10 Years

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 …

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

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:

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

The aim of this study was to evaluate renal function changes after percutaneous transluminal renal artery angioplasty (PTRA) done to treat atheromatous renal artery stenosis with renal failure. Between 1990 and 1995, PTRA was performed in 99 renal failure patients (creatinine clearance less than 80 ml/min) with atheromatous stenosis of one or more native renal arteries. Indications for PTRA were chronic renal failure with poorly controlled hypertension (group A, 67 patients) or rapidly deteriorating renal function (group B, 32 patients). Renal function changes after PTRA were evaluated based on the percentages of patients with improved, stabilized, and worsened serum creatinine and creatinine clearance values, and on mean differences between final and baseline creatinine clearances. At the end of follow-up (19+/-10 months), group A had a significantly smaller creatinine clearance gain (42.9 ml/min before PTA to 44.5 ml/min after PTA, D=1.6 ml/min, in group A, vs 24.1-28.4 ml/min, D=4.3, in group B, p=0.03), and a significantly smaller percentage of improved patients (36 vs 62%) than group B. Most stenoses in group B either were bilateral or occurred on a solitary kidney ( p=0.001). Percutaneous transluminal renal artery angioplasty combined with aggressive medical treatment may be useful in maintaining or improving renal function, particularly in patients with a recent, sharp deterioration in renal function.

Hypertension Following Kidney Transplantation

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

To evaluate the use of percutaneous transluminal renal angioplasty (PTRA) in the treatment of renal vascular hypertension. Sequential prospective PTRA treatment of severe arterial hypertension, screening by the captopril test, confirmed by renal arteriography, and the result evaluated by post-PTRA arteriography, blood pressure measurement and renal function. SITE: Vascular Surgery, angioradiology sector, and Nephrology outpatients department of the Federal University of São Paulo-Paulista School of Medicine, São Paulo, Brazil, a tertiary health-care institution. PTRA was employed on 32 patients screened by clinical examination, captopril test and renal arteriography. PTRA results were evaluated by the criteria of the Cooperative Study of Renovascular Hypertension. After PTRA the completion arteriography showed no renal stenosis in 24 patients (75%), residual stenosis (20-50%) in 3 (9.4%) and no change in 5 (15.6%). The blood pressure results were: 3 patients (9.4%) were cured, 24 (75%) improved and 5 (15.6%) were unchanged. We observed normal renal function before and after PTRA in 25 patients (78%); altered pre- and improved post-PTRA in 2 (6.3%); post-PTRA remained unaltered in 2 (6.3%); and altered pre- and worsened post-PTRA in 3 (9.4%). Recurrence of stenosis occurred in one patient after 8 months. PTRA is a convenient procedure, relatively safe and an effective complementary method of medical therapy for controlling renovascular hypertension.

Objective: To evaluate the efficacy and the related factors of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH) by a systematic review and meta-analysis. Methods: A systematic search was performed on international and domestic databases (Pubmed, Excerpt Medical Database (EMBASE), Cochrane library, Clinical trial.gov, Medline, China Biology Medicine (CBM), China national knowledge infrastructure (CNKI), VIP database and Wanfang) which included studies on PTRA for pediatric RVH from the establishment of the databases to March 2019. Key words of "pediatric" "children" "renal artery stenosis" "renovascular hypertension" "angioplasty" and "intervention" were used. Meta-analysis was made on the rate of technical success, clinical blood pressure improvement, complication and restenosis of PTRA as well as the predictors of its efficacy. The data consolidation, analysis of heterogeneity and sensitivity, and publication bias were performed using Comprehensive meta analyst and Open meta analyst software. Results: Seventeen observational non-controlled studies comprising 384 patients with RVH who underwent PTRA were identified. The technical success rate of PTRA was 93.9% (95% confidence interval (CI) 89.3%-97.5%). The improvement rate of blood pressure was 68.4% (95%CI 57.2%-78.7%), and the cure rate was 40.0% (95%CI 25.0%-55.8%). The subsequent subgroup analysis showed that there was no significant difference in the improvement rate of blood pressure after PTRA among the patients with RVH caused by fibromuscular dysplasia, Takayasu arteritis and neurofibromatosis type 1, respectively (P>0.05). The improvement rate of blood pressure in patients with combined lesions in renal artery branches was significantly lower than that in patients with lesions only in main renal artery (RR=1.659, 95%CI 1.023-2.689, P=0.040). It was found that 25.5% (95% CI 19.3%-32.2%) of patients required repeat procedure because of restenosis of lesions. Procedural complication of PTRA occurred in 8.3% (95%CI 3.5%-14.4%) of patients. In terms of clinical blood pressure improvement rate after PTRA, there was heterogeneity among the enrolled studies, but the results of meta-analysis were robust with low risk of publication bias (t=1.690, 95%CI -0.363-3.124, P=0.110). Conclusion: The result of the Meta-analysis suggests that PTRA may provide a safe and effective treatment for pediatric RVH, and patients with stenosis of renal arterial branches are associated with relatively poor clinical outcomes.

No. 322: Percutaneous transluminal renal angioplasty for renovascular hypertension in pediatric patients with moyamoya disease

Background: We have previously shown in patients with renovascular hypertension (RVH) that elevated urinary mtDNA copy numbers represent surrogate markers of renal mitochondrial injury. Revascularization with percutaneous transluminal renal angioplasty (PTRA) can lead to acute renal reperfusion injury. However, whether PTRA induces renal mitochondrial injury remains unknown. Methods: We prospectively measured urinary copy number of the mtDNA genes cytochrome-c oxidase-3 (COX3) and NADH dehydrogenase subunit-1 (ND1) by qPCR in 5 RVH patients before and 24hrs after PTRA. Five additional patients were treated before and during PTRA with the mitoprotective drug elamipretide (ELAM, 0.05 mg/kg/hr IV infusion). Healthy volunteers (HV) served as controls (n=5). Results: Baseline blood pressure was similarly elevated in both RVH groups, and eGFR lower than HV (Table). Baseline urinary COX3 and ND1 levels were similarly higher in both RVH groups compared with HV (Fig. A), and directly correlated with serum creatinine levels (R 2 =0.74, p=0.001 and R 2 =0.45, p=0.033, respectively). Over 3 months, eGFR increased only in ELAM-treated patients (Fig. B). Furthermore, the rise in urinary mtDNA 24hrs after PTRA was blunted in PTRA+ELAM versus PTRA+Placebo, and inversely correlated with the change in eGFR of 3 months after PTRA (Fig. C). Conclusion: PTRA induces an acute rise in urinary mtDNA levels, likely reflecting renal mitochondrial injury due to reperfusion injury that inhibits renal recovery. Mitoprotection in this cohort limited PTRA-associated mitochondrial injury and improved renal outcomes after revascularization.

To evaluate the efficacy and safety of percutaneous transluminal renal angioplasty (PTRA) in children. We performed aortography and attempted PTRA in 35 consecutive children (age 5 to 14 years, mean 10.8 +/- 2.5 years) with severe hypertension having > or = 75% renal artery stenosis (RAS). The stenosis was caused by aortoarteritis in 31 (88.6%) cases and by juvenile idiopathic fibromuscular disease (FMD) in four (11.4%) cases. Twenty-seven (77.1%) patients, including three having RAS of solitary functioning kidney with total occlusion of contralateral renal artery, had bilateral RAS and eight (22.9%) had unilateral RAS. PTRA was technically successful in 54 (91.5%) of 59 stenotic lesions in 31 (88.6%) of 35 patients. Both aortoarteritis and FMD patients had significant decrease in RAS after PTRA. One patient had acute reocclusion of one renal artery after bilateral PTRA, which could be successfully opened by reangioplasty. Postangioplasty angiographic restudy performed in 18 patients at 4 to 72 months (mean 23.1 +/- 27.9 months) after successful angioplasty showed restenosis in 8 (25.8%) of 31 lesions initially dilated and de novo lesions of aorta in two patients. All seven restenotic renal artery lesions attempted and both stenosis of aorta were successfully dilated. Twenty-nine of 31 patients with successful PTRA have been followed up from 4 to 108 months (mean 41.0 +/- 29.3 months). Mean systolic blood pressure decreased from 185.1 +/- 27.4 to 120.6 +/- 19.2 mm Hg and mean diastolic blood pressure decreased from 118.4 +/- 13.2 to 84.6 +/- 10.4 mm Hg after PTRA. Twenty seven (93.1%) of these 29 patients had benefical blood pressure response. Seventeen (58.6%) patients improved, 10 (34.5%) were cured, although 2 (6.9%) patients failed to respond to PTRA. Blood pressure response was better in FMD as compared to aortoarteritis group. Patients with unilateral RAS, discrete stenosis, and post-PTRA stenosis < or = 20% also identified good blood pressure response. Aortoarteritis is the most common cause of renovascular hypertension in South Asian children. PTRA is safe and highly effective and therefore should be the treatment of choice in pediatric renovascular hypertension.

Tc99m-dimercaptosuccinic acid renal uptake (DMSA uptake) was examined to assess the changes in split renal function following percutaneous transluminal renal angioplasty (PTRA) in 9 patients with a total of 12 renal artery stenoses and renovascular hypertension (RVH). The results were studied with respect to age, degree of renal artery stenosis, and renal vein renin ratio (RVRR) before PTRA. Although the degree of renal artery stenosis, systolic blood pressure, and peripheral blood plasma renin activity were improved 3 months after PTRA, neither the DMSA uptake of the affected kidneys nor that of the contralateral kidneys improved. Although restenosis occurred during the long follow-up period in one patient, DMSA uptake did not change in parallel with the degree of stenosis or RVRR. The degree of improvement in DMSA uptake, blood pressure, and plasma renin activity after PTRA in patients aged under 70 years was significantly higher than that in patients 70 years or older. Good improvement of renal function was attained in a 4-year-old boy, despite the fact that split renal function prior to PTRA was so poor that nephrectomy had been considered instead of PTRA. These results suggest that several factors before PTRA, such as DMSA uptake, degree of renal artery stenosis, and RVRR, are not absolutely predictive of results after PTRA, and that the effect of PTRA on blood pressure and renal function is greater in younger patients.

Atherosclerotic renal arterial stenosis (ARAS) is a common complication in elderly patients with chronic kidney disease (CKD). It has been reported that 5–22% of elderly CKD patients are affected by ARAS [1]. ARAS often causes severe renovascular hypertension that is difficult to treat with antihypertensive combination regimens. As angiotensin is generally recognized to be responsible for renovascular hypertension, a recent report has suggested that treatment with angiotensinconverting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) is beneficial for RAS patients by leading to lower cardiovascular event rates and reducing the requirement for dialysis [2]. However, these benefits come with considerable risk for hospitalization for rapidly progressive renal dysfunction in some ARAS population by excessive reduction of glomerular filtration pressure [2, 3]. Moreover, ARAS is associated with a high annual death rate of 16%, mainly due to cardiovascular events [4], and is a predictor for death independent of other conventional cardiovascular risk factors [5, 6]. ARAS is a clinical condition that is distressing to nephrologists or interventional cardiologists engaged in treatment, because the benefits of percutaneous transluminal renal angioplasty (PTRA) and stenting of the renal arteries in ARAS patients has been a topic of debate. A meta-analysis of three randomized trials [7–9] comparing conventional medication with PTRA revealed that PTRAwas not therapeutically beneficial to blood pressure control in ARAS patients, even though it had a significant effect in reducing the dosage of medication [10]. In focusing on renal deterioration, two large trials showed that renal arterial stenting had no benefit over medical therapy in outcomes relating to blood pressure, preservation of renal function and mortality [11, 12]. Thus, there is yet no evidence from clinical trials that revascularization reduces the incidence of end-stage renal disease in patients with ARAS. A possible reason for these negative findings is that some of the subjects in the trials had no room for renal improvement by PTRA at the time of entry. Although insufficient efficacy of revascularization on renal outcome in ARAS patients has been evidenced in several clinical trials, there may be hope that revascularization improves renal function in some populations of ARAS patients. Development of an examination to evaluate renal function is needed to determine which ARAS patients might benefit from revascularization and subsequent follow-up management until therapeutic intervention. The severity of RAS is assumed to be a predictor for ischemic nephropathy, but it has been documented that severity of RAS only weakly relates to the presence of ischemic nephropathy, as reported in a previous study showing that the severity of proximal renal artery lesions was often unassociated with renal dysfunction in ARAS patients [13]. Thus, other feasible mechanisms beyond hemodynamic decrement seem to influence the pathogenesis of RAS-mediated parenchymal damage, and this should be considered in deciding when and to whom therapeutic intervention should be applied. Lerman et al. [14–22] at the Mayo Clinic, Rochester, MN, have consistently and intensively investigated the efficient evaluation and treatment for post-stenotic kidneys in ARAS by using immunological approaches. These investigators have recently demonstrated the significance of elevated inflammatory cytokines/chemokines, including interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6, and of CD68+ macrophage expansion for the evaluation of severity of damage to the human post-stenotic kidney with ARAS [16, 19]. Lerman et al. also showed a strong association between reduction of these elevated cytokines/chemokines in stenotic kidneys and renal functional recovery after revascularization in an experimental swine model of ARAS [15]. Therefore, it is anticipated that treatments to modulate pro-inflammatory cytokines/chemokines in post-stenotic kidneys can attenuate renal dysfunction in post-stenotic kidneys and improve renal prognosis after revascularization in the ARAS population. IN F O C U S

This study evaluated the long-term effects of percutaneous transluminal renal angioplasty (PTRA) on blood pressure and renal function in patients with renovascular hypertension. Seventy-eight patients with hypertension and unilateral or bilateral stenoses of the renal arteries (16 with fibromuscular dysplasia and 62 with atherosclerosis) were studied. All patients with fibromuscular dysplasia (group A) had normal renal function, while 27 of the 62 patients with atherosclerosis (group B) presented with various degrees of renal failure. PTRA was technically successful in 87.5% patients of group A. The overall technical success rate (complete plus partial) was 72.3% (55/76 renal arteries) in group B. Mean follow-up (range) in months was 42 (12-108) for group A and 39 (13-106) for group B. After successful PTRA, the overall benefit rate (cure plus improved) for hypertension was 100% in group A; 10 of 14 patients were cured and 4 of 14 were improved. In group B, the overall benefit rate was 70.8%; 9 of 48 were cured and 25 of 48 were improved. PTRA was technically successful in 18 of 27 patients with renal failure. Renal function improved in 4 of 18 patients, remained stable in 9 of 18, and deteriorated in 5 of 18 patients. The above results suggest that PTRA is an effective method for the long-term management of patients with renovascular hypertension, although the results were less favorable in the presence of bilateral renal artery stenoses: in addition to improved control of blood pressure, PTRA might improve renal function or delay its progressive deterioration.