Our study showed that in patients with RAS and clinically high-risk features, renal artery stenting resulted in a very good short-term survival, without recurrence of cardiac destabilization syndromes.

Since most of the patients included in our analysis presented an acute or subacute clinical picture, the short-term effect of revascularization was evident during the hospital stay, as cardiac destabilization syndromes resolved and creatinine level stabilized. No major cardiovascular events (death or myocardial infarction) occurred. Stenting procedure was safe, with only one periprocedural vascular access complication, managed medically.

Nevertheless, long-term mortality was high, around 33% at two years of follow-up, suggesting the severe general cardiovascular disease burden of these patients. However, the high long-term mortality was consistent with other previous studies; Ritchi et al. showed a mortality of 56% in the medical group and 52% in the stenting group, at 3.8 years of follow-up [3].

Regarding the impact of stenting on renal function, some improvement was observed with respect to preprocedural creatinine levels. Yet, when compared to baseline levels (renal function before the rapid decline that had precipitated the hospitalization), pre-discharge median creatinine levels were somewhat higher. It seems that the initial acute rise of creatinine level is not fully reversible in all patients, with a few having their status aggravated by the procedure itself. However, significant creatinine level fall was noted in patients with initial rapidly declining renal function, suggesting the curative nature of the procedure in these patients. In the absence of revascularization, evolution would probably have been very fast toward end-stage renal disease (ESRD) in this subgroup, as suggested by the evolution of the patient with late stent occlusion.

Data from both randomized and observational trials underlie the need for appropriate selection of patients undergoing renal artery revascularization [6]. Randomized trials [9,10,11,12] have shown that revascularization does not alter clinical outcomes, compared to medical therapy alone, especially because the low-risk patients have little benefit [6, 9].

Nevertheless, observational studies provide consistent evidence of benefit of revascularization concerning different outcomes (major adverse events, ESRD, recurrence of cardiac destabilization syndromes) in RAS patients with high-risk features [3, 8, 13]. The discrepancy between randomized and observational trials is probably driven by the difference between patients included [4, 14].

In a large group of patients with RAS treated medically, Ritchie et al. showed that of the three high-risk presentations (FPE, rapidly declining renal function, and refractory hypertension), only FPE is a significant adverse prognostic marker [3]. We did not use refractory hypertension as high-risk criterion because it has various definitions and the data on its appropriateness as a high-risk feature are contradictory.

An important concept for a good selection of patients most likely to benefit after revascularization is "global renal ischemia" [1]. In unilateral RAS, the hypertension induced by angiotensin-aldosterone activation is partially compensated by pressure natriuresis in the contralateral, non-ischemic kidney [15]. This is not the case in severe bilateral RAS (Fig. 2). Vassallo et al. [8] underlined the importance of severe bilateral RAS in predicting a revascularization benefit, showing that, even in high-risk patients, likelihood of benefit is higher in patients with severe bilateral RAS and low levels of proteinuria. Therefore, we also included in our research patients with chronic renal failure and significant, bilateral renal artery disease (or unique functional kidney).

Bilateral renal artery stenosis in a patient with flash pulmonary edema and rapidly declining renal function. The tight stenosis on the right renal artery (panel A) was stented (panel C) with a good final result (panel D). The subocluded left renal artery (Panel B) subtended a small kidney (presumably, non-viable). Serum creatinine normalized 72 h after the procedure, there were no recurrences of pulmonary edema at 2 years of follow-up and hypertension was controlled with a single drug

Timely revascularization reduces renal ischemia and renin–angiotensin–aldosterone system activation, reducing blood pressure and leading to clinical stabilization [8], finally, increasing survival and reducing further hospitalizations in these patients [16, 17]. A large study showed that in patients with RAS and history of recurrent heart failure, 82% of the successfully stented patients had no hospitalization during follow-up [13]. Patients with FPE due to RAS showed marked weight reduction following stenting, due to the intense diuresis [18].

Different studies showed long-term high mortality rates in RAS patients presenting with high-risk features, reaching 12% per year and up to 56% at four years [3, 19, 20]. In some studies, the survival benefit was observed only in patients with FPE [3] and, inconsistently between studies, in those with rapidly declining renal function [3]. In our group of high-risk RAS patients undergoing stenting, 33% mortality was observed on a follow-up of roughly 2 years.

Regarding postprocedural renal function, in our group was observed a rather equivocal response to angioplasty. Overall, improvement of the preprocedural renal function was observed in half of the patients. The expected result was somewhat masked by CIN, which occurred in a third of patients, entirely reversible in the majority of patients, but a net positive effect of angioplasty became finally visible only in two of six patients with CIN. On the other hand, when compared to baseline renal function (before the index hospitalization decline), pre-discharge creatinine levels were steady.

Similarly, renal failure improvement after stenting was inconsistent across different studies [21], with no change [22, 23] or even worsening in a significant proportion of the patients [19, 20]. However, there are studies showing that stenting improves or at least stabilizes renal function, especially in RAS patients with a rapid decline of function in the year before intervention [24,25,26], usually in patients with bilateral or solitary kidney stenosis [24]. Non-responders to revascularization are generally patients with stable reduced renal function before intervention [2].

Different studies showed inconsistent results regarding the progression to ESRD [3, 8, 13, 19, 23]. Ritchie et al. showed 18% progression to ESRD at 3.8 years, without difference between stenting and medical approach, in patients with high-risk features [3]. In our small group of stented high-risk RAS patients, roughly a quarter ended-up on hemodialysis after two years of follow-up. The predictors of ESRD were diabetes and baseline renal failure, suggesting as cause the progression of underlying renal parenchymal disease rather than renal vascular disease. Diabetes is an established independent cause of ESRD due to microvascular complications [8]. There was no improvement after revascularization in patients with proteinuria > 1 g/day [8]. In order to estimate the benefit of revascularization in ischemic nephropathy, the relative contribution of RAS and intrinsic nephropathy to renal failure should be assessed by urinalysis (proteinuria), renal size (by imaging), renal resistive indexes, serum creatinine or estimated glomerular filtration rate. Pre-treatment eGFR of < 30 ml/min and severely increased albumin to creatinine ratio were each independent predictors of worse outcome [27].

Predictors of a positive response to stenting are deterioration of renal function after angiotensin converting enzyme inhibitors, rapid decline of renal function, kidney dimension > 8 cm, no signs of cortical or interstitial fibrosis [7], or preoperative resistive index up to 0.75 [28, 29].

Studies have shown that revascularization has little impact on hypertension control (1–20%) [30, 31]. However, our study demonstrated better hypertension control after two years of follow-up, but this could not be entirely attributed to revascularization.

Retrospective nature of the research and the low number of patients are the main drawbacks of our study. The results are attributed to procedures performed during a long period, implying different renal angioplasty techniques and devices. Baseline data on renal disease reversibility, as proteinuria, resistivity index and kidney size were lacking for analysis. In addition, functional evaluation of the severity of RAS was not available; however, in general, we treated tight stenoses (> 70%), leaving little doubt on their significance. We did not have a medically treated controlled group, because in patients with high risk RAS there is no equipoise between the two possible treating strategies (stenting vs. conservative treatment), hence the descriptive nature of our study. As the follow-up was made by telephone contact, no direct clinical or laboratory data could be obtained.