Refractory hypertension with massive proteinuria may be reversed in renal artery stenosis patients with low proteinuria selectivity index after stenting.

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

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

Objectives The selectivity index has been proposed in predicting the response to immunosuppressive therapy in nephrotic syndrome and other primary kidney disorders. The aim of this study was to elucidate the predictive value of the selectivity index for the treatment response and renal outcome in patients with lupus nephritis. Methods Forty-four patients with lupus nephritis with selectivity index available at the time of renal biopsy were divided into two groups according to the cut-off value of the selectivity index determined by a receiver operating characteristics curve to differentiate treatment responders from non-responders. The baseline characteristics, overall response rate and renal functional outcome were studied retrospectively, and compared between the two groups. Prognostic factors for achieving remission were identified. Results The cut-off value of the selectivity index was 0.167. The low selectivity index (<0.167) and the high selectivity index (≥0.167) group included 24 and 20 patients, respectively. The overall response rate was significantly higher (88% vs. 50%, P = 0.007) and the rate of progression to end-stage renal disease was lower in the low selectivity index group (0% vs. 15%, P = 0.049). More patients in the high selectivity index group had chronic lesions on renal biopsy ( P = 0.002). The selectivity index was the prognostic factor for achieving overall response based on a multivariate analysis ( P = 0.020). Conclusions A selectivity index ≥0.167 was a strong predictor for a poor treatment response and the presence of chronic lesions on renal biopsy. Further exploration with a larger cohort and longer follow-up period is warranted.

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 artery stent revascularization with embolic protection in patients with ischemic nephropathy

Atherosclerotic renal artery stenosis (ARAS) causes hypertension (HTN) and threatens renal function (RF). The HERCULES Trial is a prospective, multicenter trial of renal stenting in patients with uncontrolled HTN and ARAS evaluating the safety and effectiveness of the RX Herculink Elite Renal Stent System (Abbott Vascular, Santa Clara, CA). A total of 202 patients (241 total lesions; 78 bilateral lesions) were enrolled between August 2007 and October 2009. The primary endpoint was 9-month binary restenosis determined by duplex ultrasound and/or angiography. Secondary endpoints included changes in blood pressure, antihypertensive medications, and RF between baseline and 9 months. Brain natriuretic peptide (BNP) was measured at baseline, 24 hr and 30 days postprocedure. Mean systolic blood pressure (SBP) at baseline was 162 mm Hg. Nearly 70% of patients were receiving three or more antihypertensive medications (mean 3.4 medications per patient). Baseline serum creatinine was 1.2 ± 0.4 and 61.5% of subjects had estimated glomerular filtration <60. The restenosis rate was 10.5% at 9 months. The study device, procedure, and clinical success rates were 96.0, 99.2, and 98.0%, respectively. Freedom from major adverse events was 94.8%. At 9 months, the mean SBP significantly decreased (mean 145, paired t test P < 0.0001) after stenting with no change in medications. There was no correlation between SBP reduction and baseline BNP or BNP reduction. HERCULES demonstrates clinically and statistically significant SBP reduction in patients with uncontrolled HTN, low in-stent restenosis, and complication rates. This study highlights that when appropriate patients are selected for renal artery stenting, impressive reductions in blood pressure may be anticipated. Although the magnitude of absolute reduction in SBP was related to baseline SBP, elevated baseline BNP levels were not predictive of reduction in SBP. Further studies for predictors of clinical response following percutaneous renal revascularization are needed.

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 …

The proteinuria selectivity index (SI) is a valuable marker of glomerular permeability. Traditionally, SI has been calculated using the clearance ratio of immunoglobulin G (IgG) to transferrin-SI (Tf)-due to historical limitations in albumin measurement accuracy. However, recent advances have enabled precise quantification of albumin, raising the possibility of using an albumin-based SI-SI (Alb)-in clinical practice. This study aimed to evaluate the correlation between SI (Alb) and SI (Tf) and to compare their diagnostic utility in patients with proteinuria. We retrospectively analyzed 265 patients with proteinuria > 0.15g/g·Cr who visited Ehime University Hospital between January 2014 and April 2024. SI (Alb) and SI (Tf) were calculated as the clearance ratios of IgG to albumin and IgG to transferrin, respectively. Linear regression was used to assess their correlation. Diagnostic performance for minimal change disease (MCD) in patients with nephrotic-range proteinuria (≥ 3.5g/g·Cr) was evaluated using ROC curves, and AUCs were compared using DeLong's test. SI (Alb) strongly correlated with SI (Tf) in patients with proteinuria ≥ 3.5 and < 3.5g/g·Cr. Among patients with nephrotic-range proteinuria, both indices effectively identified MCD, yielding comparable areas under the ROC curve. Sensitivity and specificity at optimal thresholds were similarly high. SI (Alb) shows a high degree of concordance with SI (Tf) and offers comparable diagnostic accuracy for identifying MCD. Given its practical advantages, SI (Alb) may serve as a reliable and convenient alternative to SI (Tf) for assessing glomerular selectivity in patients with proteinuria.

The Need for Randomized Trials to Prove the Safety and Efficacy of Parachutes, Bulletproof Vests, and Percutaneous Renal Intervention

Renal artery stenosis may play a significant role in the pathogenesis of secondary hypertension, renal dysfunction, and flash pulmonary edema. Currently correction of renal arterial inflow stenosis is reserved for resistant hypertension patients who have failed maximal medical therapy, have worsening renal function and/or unexplained proximal congestive failure. With the recent advances in minimally invasive percutaneous stent placement techniques, open surgical revascularization has been largely replaced by renal artery stenting. The potential benefit of revascularization seemed intuitive; however, the initial enthusiasm and rise in the number of percutaneous interventions have been tempered by many subsequent negative randomized clinical trials that failed to prove the proposed benefits of the percutaneous intervention. The negative randomized trial results have fallen under scrutiny due to trial design concerns and inconsistent outcomes of these studies compared to pivotal trials undertaken under US Food and Drug Administration scrutiny. Treatment of atherosclerotic renal artery occlusive disease has become one of the most debatable topics in the field of vascular disease. The results from recent randomized clinical trials of renal artery stenting have basically limited the utilization of the procedure in many centers, but not every clinical scenario was covered in those trials. There are potential areas for improvement focusing mainly on procedural details and patient selection with respect to catheter based treatment of atherosclerotic renal artery stenosis. We believe, limiting patient selection, enrollment criteria and outcomes measured functioned to reduce the benefit of renal artery stenosis stenting by not enrolling patients likely to benefit. Future studies incorporating potential procedural improvements and that include patients more likely to benefit from renal stenting than were included in ASTRAL and CORAL are needed to more carefully examine specific patient subgroups so that "the baby is not thrown out with the bath water." We also discuss several other concerns related to renal artery stenting which include diagnostic, procedure, indication, and reimbursement issues.

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

Analysis of the Third National Health and Nutrition Examination Survey (1988 to 1994) suggests that chronic kidney disease (CKD) is a major public health problem (1). Approximately 11% of the US population has CKD. Roughly half have a GFR <60 ml/min per 1.73 m2 with or without kidney damage (stages 3 to 4), and half have exclusively kidney damage as manifested by microalbuminuria (stages 1 to 2) (2). It is widely recognized that the prevalence of stage 5 CKD is also increasing at a rapid rate, and it is estimated that the number of patients who have ESRD may reach 2.24 million by 2030 (3). Evidence to establish reduced GFR as an independent risk factor for cardiovascular disease (CVD) mortality has emerged. Analysis of data from several population-based epidemiologic studies (4,5) demonstrates poorer outcomes regarding stroke, myocardial infarction, and congestive heart failure (CHF) in patients with even mild compromise of kidney function. The morbidity of this group of patients constitutes an economic burden both directly in terms of resource utilization and indirectly through loss of productivity and impaired quality of life (2). Atherosclerotic renovascular disease (ARVD) can result in renovascular hypertension. However, ARVD is an increasingly recognized cause of CKD (6,7). In this article, we focus mainly on ARVD or renal artery stenosis (RAS) secondary to atherosclerosis as a cause of ischemic nephropathy. ARVD is a disease of aging, and several studies have shown its strong association with extrarenal atherosclerotic disease (8–10). Patients with ARVD seem to be at a much greater risk for cardiovascular death than for progressing to renal replacement therapy (11). Whether renal revascularization can benefit renal and cardiovascular outcomes has not been established. Atherosclerosis is the cause of approximately 90% of RAS in adults who are older …

A New Era of Renal Denervation Trials for Patients With Hypertension?

When and How Should We Revascularize Patients With Atherosclerotic Renal Artery Stenosis?