Atherosclerotic renal artery stenosis (ARAS) is the most common cause of renal artery stenosis (RAS) and is associated with severe comorbidities such as resistant hypertension, ischemic nephropathy, and end-stage renal disease [1,2]. Common therapeutic strategies for RAS include medical therapy, angioplasty with or without stenting, and bypass surgery. Percutaneous transluminal angioplasty (PTA) is a highly effective modality for correction of RAS. However, two recent randomized controlled trials (RCT) of PTA for ARAS failed to demonstrate any advantages compared with conventional medical therapy regarding renal protection or prevention of cardiovascular events [3–6]. Nevertheless, ARAS frequently progresses despite adequate medical management and results in irreversible renal atrophy. Thus, timely corrections of RAS through PTA with stent insertion (PTA/S) may have a beneficial effect on long-term renal outcomes in selected patients.

Current guidelines for ARAS recommend PTA as a reasonable option for patients with haemodynamically significant RAS with clinical manifestations such as resistant hypertension, unexplained pulmonary edema, or progressive chronic kidney disease [7,8]. However, patient selection for renal revascularization is sometimes challenging, because limited comparative data are available on the specific phenotype of patients who would benefit from the procedure [9–11]. In this study, we investigated the effects of renal revascularization in terms of kidney function and blood pressure (BP) control in patients who received PTA/S for ARAS, classifying subjects into low-risk and high-risk groups. High-risk was defined by clinical presentation including a history of pulmonary edema, refractory hypertension, or rapid deterioration of kidney function accompanied by RAS.

The present study demonstrated that patients with ARAS presenting with high-risk clinical manifestations might benefit from revascularization, which is consistent with previous studies [9,22]. We found that subjects with rapid deterioration of kidney function showed kidney function improvement, and those with refractory hypertension achieved better control of BP, with a decrease in the number of antihypertensive medications after PTA/S, compared to the low-risk group. In addition, this study suggested that, even if baseline eGFR is < 30 mL/min/1.73 m², PTA/S may be considered as a treatment option in patients with clinically significant ARAS.

Optimal medical treatment without revascularization has been the ‘gold standard’ for low-risk and stable ARAS, according to a previously reported RCT and meta-analysis [10]. Recently, the two largest RCTs evaluating percutaneous renal artery intervention for RAS, the CORAL trial and the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial, demonstrated that revascularization did not offer significant benefits over medical therapy in patients with ARAS and stable chronic kidney disease [3,4]. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, such as episodic pulmonary edema, rapid decline of kidney function, and hypertension [23].

In the ASTRAL trial [3], the primary outcome measure was change in renal function over time. During a median follow-up period of 34 months, the rate of progression of renal impairment differed, being lower in the revascularization group at 0.06 × 10⁻³ L/μmol per year (95% confidence interval, −0.002 to 0.13; P = 0.06). There were no between-group differences in the following secondary outcomes: SBP/DBP, rates of renal events, major cardiovascular events, and death. However, the majority of the patients in the ASTRAL trial had only mild-to-moderate RAS, and about 40% of subjects had a stenosis < 50% and were least likely to benefit from revascularization. Twenty-five percent of subjects had normal renal function and a further 15% almost-normal renal function at baseline. The aim of the CORAL trial [4] was to evaluate “hard” clinical endpoints using cardiovascular or renal events. Over a median follow-up period of 43 months, there were no significant differences between the treatment groups in primary outcomes and overall survival. The original study protocol included patients with 60% to 100% RAS on angiography, with an SBP above 155 mmHg, and taking two or more anti-hypertensive medications. However, there have been changes in the original inclusion criteria due to slow enrollment. As a result, 25% to 30% of patients have shown well-controlled BP, 55% of subjects had < 70% stenosis, and approximately 50% of the cohort presented normal kidney function.

There have been several studies reporting the benefits of revascularization in high-risk patients with ARAS [8,9,22,24]. Patients presenting with a combination of rapidly declining kidney function and refractory hypertension may benefit from revascularization [22]. Vassallo et al. [9] have recently demonstrated that high-risk patients, especially those presenting with rapidly deteriorating renal function and concurrent bilateral ≥ 70% RAS and low levels of proteinuria (< 1 g/day) at the time of diagnosis, benefited from revascularization. In their study, high-risk patients were defined as those presenting with ≥ 70% unilateral or bilateral angiographic RAS with at least one high-risk clinical manifestation such as flash pulmonary edema, stage 2 hypertension, or rapidly deteriorating renal function. The study used stricter inclusion criteria for uncontrolled or severe hypertension (SBP ≥ 160 mmHg and/or DBP ≥ 100 mmHg) than the present study. In addition, the definition of rapidly declining kidney function differed from that of the present study, as the eGFR slope was defined as less than −3.0 mL/min/1.73 m²/year. In our study, 58% of subjects with baseline uPCR < 1 mg/mg Cr showed an improvement in kidney function or better control of BP. None of the patients with baseline uPCR > 1 g/g Cr showed any increase in kidney function after PTA/S (data not shown), but this was not statistically significant, which was likely due to the limited number of patients. Proteinuria may imply the presence of comorbid renal parenchymal disease [25,26]. In this circumstance, the revascularization of RAS may have little impact on the outcome of kidney disease. In addition, none of the patients with a targeted arterial stenosis < 75% showed any benefit on revascularization in the present study. These results are consistent with the finding that a RAS greater than 70%–80% is necessary to activate intra-renal RAS [23], although identification of haemodynamic significance by anatomical stenotic severity is limited [11,27–29].

There are several limitations to be mentioned. First, as this was a retrospective study, patients were not randomized to revascularization; hence, selection bias and potential hidden confounders may affect the results. However, considering that recruitment to renal stenting trials is very challenging (e.g., the recruitment phase in the ASTRAL study lasted seven years and approximately two patients per year were enrolled) [3], our findings based on retrospective data are worthy of attention. Second, this study was a small single-arm registry study without comparison with an optimal medical therapy arm. Thus, the generalizability of our findings remains to be determined. Third, because of the relatively short follow-up period, we did not examine the effects of revascularization on the long-term effects on the kidney or the patient. Instead, immediate changes in BP and kidney function were evaluated in detail.

The present study investigated the clinical efficacy of revascularization in patients with ARAS and suggested beneficial effects of revascularization on hypertension and kidney function in patients who presented with high-risk clinical features. Patients with stenosis < 75% showed poorer responses to PTA/S, while an advanced chronic kidney disease stage was not a predictor of poor response to PTA/S. Two recent RCTs of PTA for ARAS failed to demonstrate any advantages on renal protection or prevention of cardiovascular events compared with conventional medical therapy. This study implied that the optimal application of PTA/S should be based on individual assessment of the clinical significance of RAS.