Study design and population

All patients presenting to our centre and its referring hospitals with radiological findings of at least one renal artery stenosis lesion > 50% between January 2015 and January 2020 were reviewed at the renovascular multidisciplinary team meeting in accordance with international guidelines from both the European Society of Cardiology (ESC) [11] and American Heart Association (AHA) [12].

The diagnosis of atherosclerotic renal artery stenosis was established based on computed tomography angiographic or magnetic resonance angiographic findings consistent with a renal artery lesion of ≥ 50% of the lumen based on visual assessment. Computed tomography or contrast enhanced magnetic resonance angiography were the preferred screening investigations, however, in those with stage 4 chronic kidney disease (CKD) or worse (i.e. glomerular filtration rate (GFR) < 30 ml/min), non-contrast magnetic resonance angiography was utilised. The sequence used for non contrast magnetic resonance angiography was a 3D steady state free precession with in-flow inversion recovery (Inhance, GE Healthcare).

Patients with findings consistent with fibromuscular dysplasia or large vessel vasculitis were excluded in this analysis. Patients with a significant atherosclerotic lesion and a clinical phenotype of severe hypertension, decompensated heart failure syndrome or deteriorating renal function were referred to the nephrology team by specialists in cardiology, nephrology, stroke medicine and general medicine and then discussed at the multidisciplinary team meeting along with the relevant imaging.

Description of the multi-disciplinary meeting

The multidisciplinary team meeting was held once a month. The team consisted of at least two nephrologists, an interventional radiologist and, when required, a referral was made to vascular surgery. Many of the referrals originated from colleagues in cardiology reviewing patients with hypertension or cardiomyopathy.

The discussion of each patient’s case involved a review of their electronic patient record taking note of the clinical presentation, their medical history and co-morbidities, blood pressure, laboratory data (notably prior renal function changes and level of proteinuria), and any cardiac history/complaints.

The interventional radiologist presented the radiological findings and description of the renal artery stenosis lesion and whether or not it would be amenable to renal artery stenting. The referring physician highlighted whether the patient was asymptomatic or whether a clinical indication for revascularization existed. The decision regarding whether to proceed to revascularization was based on three components, all of which were considered relevant:

High-grade renal artery stenosis lesion.

the state of the kidney beyond the renal artery stenosis (kidney size ≥ 8 cm, and review of level of proteinuria).

the clinical presentation of the patient.

Clinical aspects favouring revascularization included resistant hypertension (blood pressure ≥ 140/90 despite the use of three or more anti-hypertensive agents), deteriorating renal function not otherwise explained, sudden onset pulmonary oedema or recurrent admissions for heart failure, a renal artery stenosis lesion ≥ 75% affecting a solitary kidney. A high-grade renal artery stenosis was a lesion > 75% of the lumen diameter or those with radiologic evidence suggesting compromised blood flow [13].

Patients were revascularized according to priority, with inpatients with acute kidney injury (AKI) or those with severe renal artery stenosis and worse clinical picture being expedited.

Proteinuria is a significant marker of established renal parenchymal damage and has been shown as an independent predictor of worse outcomes in those with ischaemic nephropathy. Significant albuminuria (urine albumin creatinine ratio, (ACR), > 30 mg/mmol) or proteinuria (urine protein creatinine ratio, (PCR), > 50 mg/mol) are independent predictors of worse outcomes in patients revascularized for hypertension [14].

Clinical aspects that would argue against revascularization were clinical frailty, multiple co-morbidities, lesions of 100% without clinical features of renal artery sclerosis or an atrophic kidney with length < 8 cm.

Multiple comorbidity refers to disease in several organ systems, which in the opinion of the managing physician implied that a revascularization procedure would be high risk or futile. Frailty was assessed by the Clinical Frailty Scale [15].

Each member of the multi-disciplinary team gave their opinion regarding the risks and potential benefits of revascularization followed by a comprehensive discussion to reach a consensus. If the computed tomography or magnetic resonance angiography image quality was inadequate, further imaging was arranged with a planned discussion at a subsequent meeting.

If the decision was to proceed with revascularization, then the patient was notified, and the interventional radiologist made arrangements to meet with them to counsel on risks and benefits of the procedure before proceeding with renal artery angioplasty and stenting at a later date. Those patients with no clinical indication for revascularization were informed of the decision and if they had significant anatomical renal artery stenosis, they remained under long term follow up in our centre’s renovascular clinics, where note would be taken of any change in clinical circumstances that might lead to a change of plan.

Baseline and follow-up data

For this study, all medical records and medical correspondence of the patients considered in the renovascular multidisciplinary team meeting were reviewed. Resistant hypertension was defined as blood pressure > 140/90 mmHg despite three different classes of anti-hypertensive agents, one of which was a diuretic.

Renal function was based on estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease-Epidemiology Collaboration formula (CKD-EPI). Deteriorating renal function was defined as a decrease in eGFR of ≥ 30% from baseline in the absence of an alternative aetiology.

Blood pressure readings were the most recent clinical measurement at the time of multidisciplinary team discussion. Our standard protocol is to obtain three consecutive blood pressure readings when sitting quietly for a period of ten minutes with the lowest reading being recorded. Follow-up data included blood pressure readings taken at our unit 1 month post-revascularisation and annually thereafter. In the non-revascularized group, annual blood pressures were recorded from our centre’s electronic patient record or clinical correspondence from referring units. For patients with bilateral renal artery stenosis, the worst affected side was recorded.

For each patient, the decision of either medical management or revascularization made during the multidisciplinary meeting was noted and compared to international guidelines.

Clinical events recorded at annual follow-up included cardiovascular events and renal events in the preceding 12 months. Non-fatal cardiovascular events included acute coronary syndrome (myocardial infarction/unstable angina), cerebrovascular event (stroke or transient ischaemic event), admission for heart failure syndrome or new-onset atrial fibrillation. Renal events included severe hypertension, acute kidney injury, requirement for renal replacement therapy (RRT) (temporary or long term), transplantation or nephrectomy.

Treatment

Medical treatment of all patients was optimised according to current guidelines which included lipid-lowering agents, antiplatelet agents, anti-hypertensives agents targeting clinic blood pressure of ≤ 130/80 with the use of renin-angiotensin blocking agents where tolerated, and lifestyle modifications such as smoking cessation [16]. Patients were reviewed at regular intervals ranging from 3–6 months.

Renal artery revascularization protocol

Elective renal artery stenting procedures were usually carried out on a day case basis. The standard renal artery stenting technique consisted of ultrasound-guided common femoral arterial access secured with a 45 cm 5F Flexor ® sheath (Cook Medical). Following a renal angiogram, the stenotic lesion was crossed with an 0.35 Glidewire ® (Terumo) and catheter. An 0.18 SV-5 (Cordis) support wire would be placed in the renal artery distally. The stenotic lesion was then primarily stented with a Palmaz blue ™ (Cordis) cobalt-chromium balloon mounted bare metal stent with 1:1 sizing with the normal renal artery. Variations include arterial access from the arm (brachial or radial artery); use of a steerable sheath (OSCOR) for challenging procedures, and pre-dilatation of the lesion with a small angioplasty balloon for very tight lesions. Note was taken of any immediate complications of revascularization at the time of the procedure (e.g. dissection of the renal artery, puncture site haematoma), or complications occurring in the days post-procedure (e.g. cholesterol embolization).

At yearly follow-up, the following data were collected: systolic and diastolic blood pressure, number of anti-hypertensive agents, eGFR, urine PCR, haemoglobin, the incidence of major cardiovascular events (myocardial infarction or coronary revascularization, stroke, heart failure admission or peripheral vascular disease procedure), renal events, and mortality.

Statistical analysis

In the descriptive analysis continuous variables were reported as median and interquartile range after checking for normality of distribution with the Mann–Whitney U test. Categorical variables were expressed as number and percentage with Chi-square test used as required.

The annual rate of decline in eGFR was calculated by using all the available eGFRs between the study start and end date using linear regression analysis. Only patients with a minimum of three eGFR values and one year follow-up data were included in the linear regression analysis. The association between revascularization and all-cause mortality was shown in Kaplan–Meier plots.

Throughout the analysis a p < 0.05 was considered as statistically significant. All analyses were carried out by SPSS Version-24, registered with the University of Manchester.

Ethical considerations

The study complies with the declaration of Helsinki and was registered with the Research and Innovation department of the Northern Care Alliance NHS Group (Reference Number: 22HIP25), who approved the methodological protocol as outlined above. As this was a retrospective observational study using measurements routinely collected and fully anonymized data, the need for individual patient consent was waived by the Research and Innovation review committee, who granted study approval.