Managing acute presentations of atheromatous renal artery stenosis

Atherosclerotic renovascular disease (ARVD) often follows an asymptomatic chronic course which may be undetected for many years. The prevalence of ARVD ranges depending on the population studied. In the general asymptomatic population, it is estimated that 6.8% of the population over the age of 65 years have evidence of 50% or greater renal artery stenosis (RAS) on duplex ultrasound [1]. In those with established cardiovascular disease or significant risk factors the prevalence increases to up to 54% in those with congestive heart failure [2].

However, there are certain critical acute presentations associated with ARVD and these require a high index of suspicion for underlying high-grade RAS to improve patient outcomes. These acute presentations, which include decompensated heart failure syndromes, accelerated hypertension, rapidly declining renal function, and acute kidney injury (AKI), are usually associated with bilateral high-grade RAS (> 70% stenosis), or high-grade RAS in a solitary functioning kidney in which case the contralateral kidney is supplied by a vessel demonstrating renal artery occlusion (RAO). As the latter presentations are rarely associated with flank pain or haematuria, the consensus is that these RAO are usually chronic.

In contrast, acute RAO is a rare and organ threatening condition with varied presentations. The potential causes include thromboembolic disease, renal artery thrombosis, dissection and iatrogenic during endovascular procedure. One of the leading causes of acute occlusion is atherosclerosis. The majority of patients with acute RAO present with flank pain or with features such as fever, nausea, uncontrolled hypertension, haematuria or acute renal injury [3]. Nonspecific features can result in a delay in diagnosis which leads to delayed management and long-term sequelae such as chronic kidney disease (CKD).

Functional MRI studies measuring tissue oxygenation by blood oxygenation level dependant (BOLD) MRI have shown that when increasing severity of RAS occurs beyond 70% there is risk of progressive reduction in perfusion leading to cortical ischaemia [4]. This in turn leads to reduced renal blood flow and oxygenation within the affected kidney, with consequent activation of inflammatory pathways with increased levels of biomarkers such as neutrophil gelatinase- associated lipocalin (NGAL) ultimately leading to fibrosis [5]. For optimal patient outcome a haemodynamically significant atheromatous lesion must be identified and addressed early before the inflammatory pathway is activated.

Our centre has specialised in the management of patients with ARVD for over 3 decades, treating over 1000 patients with the condition during this time. The vast majority of patients have a sub-acute or chronic presentation. These are the patient phenotypes highly represented in the large scale randomised control trials (RCT) of stenting and medical care versus medical care alone in ARVD, namely ASTRAL and CORAL, that failed to show a benefit of revascularization to outcomes of renal function, cardiovascular events and death. Acute presentations in patients with ARVD are much less common and such patient phenotypes only had minority representation in the RCTs. Expert opinion suggests that these patients are more likely to derive a positive benefit from renal revascularization procedures, and we wish to draw attention to the classical phenotypes which should not be overlooked by describing our experience of acute ARVD presentations over the last 15 years.

In this review we have described all patients referred to our institution with acute presentations of atheromatous RAS and have characterised their presentation, imaging, treatment, and long-term outcome. We describe 9 individual patients with 3 classic presentations including accelerated phase hypertension, heart failure syndromes, anuric AKI and a fourth category of patients who suffered recurrent presentations.

The electronic health records of patients referred to Salford Royal for renal artery intervention between 2005 and 2020 were reviewed for diagnosis of “critical renal artery stenosis” or “renal artery occlusion”. Patients were included if they had complete occlusion of the renal artery or if they had an acute presentation with clinical features consistent with high-risk clinical phenotypes. This initially yielded 14 patients; 5 were excluded based on presence of trauma or other conditions such as vasculitis or fibromuscular dysplasia. In addition, their imaging in terms of CT or MR angiography was reviewed and patients were included if this confirmed the clinical suspicion of RAS which was deemed suitable for intervention. No MRA with gadolinium was performed in those with an eGFR of < 30 ml/min/1.73m² to avoid risk of nephrogenic systemic fibrosis; contrast free MRA or CTA was performed in such patients. If CTA was indicated in those with eGFR of < 30 ml/min/1.73m² a standard protocol of pre-hydration with normal saline given at a rate of 250 ml/hour for one hour pre-procedure and continued until one hour post CTA was employed to reduce the risk of contrast induced injury. Patients with ARVD without symptoms or features consistent with RAS were excluded. Data collected included demographics, co-morbidities, presentation, method of diagnosis, intervention, immediate outcomes, and long terms outcomes where available.

The 16 acute presentations of atherosclerotic RAS, treated by renal stenting, which are described in this report equated to 10% of all revascularisation procedures performed in our patients, highlighting that acute presentations are relatively uncommon (in our experience an average of one case per year in a total referral population of > 1 million) and that they necessitate a high index of suspicion and timely intervention.

All of the RAS lesions were detected by CTA or MRA, techniques which have high sensitivity and specificity for detecting significant RAS. Doppler ultrasound is also an important diagnostic and screening tool for evaluating RAS with a sensitivity and specificity for diagnosing significant RAS up to 90% and 95% respectively [19]. It is acknowledged that duplex ultrasound requires significant operator time and is not currently available in many UK centres including our own.

All our patients were revascularized using percutaneous techniques involving RAS dilatation and stent placement. Prior to availability of angioplasty surgical repair was the only option for correction of atherosclerotic renal artery disease. In modern practice percutaneous intervention has replaced surgical intervention for the management of most cases of RAS due to the associated morbidity and mortality risk of surgery. Surgery is now reserved for more complex anatomical cases, such as those with multiple small renal arteries or where aortic reconstruction is required at the origin of the renal arteries in association with aneurysm repair, where severe aortoiliac disease co-exists, and in patients in whom stenting procedures have failed [20].

The predominant acute presentation was that of acute ischaemic nephropathy as manifest by AKI or deteriorating renal function, accounting for 56% (9/16) of the presentations. Accelerated hypertension accounted for 25% (4/16) of cases with heart failure accounting for 19% (3/16) of cases. Although the characteristic presentation of acute RAO is a patient presenting with loin pain and anuric AKI this classic presentation was seen on just 2 occasions and in only one individual patient, and only in subsequent presentations rather than the original one.

Severe hypertension accounted for 25% of our acute presentation cases. Hypertension is a common co-morbidity worldwide and a leading cause of mortality. Prevention and control of hypertension decreases mortality and incidence of heart failure. The prevalence in the past two decades has been increasing possibly due to increased consumption of processed food and changes in lifestyle [21]. Up to 15% of those with hypertension will develop resistant hypertension [22].

In the general population there is a high prevalence of resistant hypertension amongst those with CKD with increasing prevalence seen with reducing renal function, ranging from 15% in those with eGFR ≥ 60 ml/min/1.73m² to 33.4% in those with eGFR < 45 ml/min/1.73m² [23]. Previous RCT such as STAR, CORAL and ASTRAL [8, 2425] have failed to demonstrate a significant benefit to patient outcome in patients with poorly controlled blood pressure or progressive renal impairment.

Other smaller studies of patients with high grade RAS that was managed medically without revascularisation found that more anti-hypertensive medications were required to effectively control blood pressure and that 5.8% of patients eventually required revascularisation [26]. In our case series, those with severe hypertension were receiving an average of 5 anti-hypertensive agents before stenting, which improved to an average of 3 agents to achieve target blood pressure post revascularisation. Our case series emphasises the need for monitoring patients with hypertension and other vascular risk factors such as atherosclerosis, smoking and dyslipidaemia to identify those most likely to benefit from revascularisation so as to reduce morbidity and mortality.

Previous studies have highlighted the benefit of revascularisation in those with heart failure with a substantial reduction in all-cause mortality and hospital admission [27]. The presence of an acute heart failure syndrome was the indication for revascularisation in 19% of the acute RAS presentations to our unit. In two of these patients there was a significant improvement in volume overload, blood pressure and renal function. One of the patients who did not benefit from stenting had previously benefitted from revascularisation on two separate occasions. There is a high prevalence of RAS amongst those with more chronic congestive heart failure ranging from 15 to 54% depending on the cohort studied and imaging modality used to identify the presence of RAS. In those with heart failure the presence of RAS is associated with worse renal outcomes and higher mortality [28].

We believe that three important considerations are necessary when contemplating renal revascularization for patients with atherosclerotic RAS. The clinical presentation is key but so too is the severity of the RAS lesion and the extent of parenchymal damage within the kidney (with better results anticipated when there is minimal proteinuria and absence of significant renal atrophy). Our case series highlighted cases compatible with the recommendations of the ACC/AHA 2018 guidelines that suggest revascularisation should be reserved for those patients with “high risk” presentations such as recurrent flash pulmonary oedema, rapidly declining renal function and refractory hypertension [29] (Fig. 3).

Acute presentations of atheromatous RAS are relatively uncommon but should be considered in patients presenting with severe hypertension, acute heart failure syndromes or with rapidly deteriorating renal function, especially AKI, particularly if there is evidence of widespread atheromatous disease. A high index of suspicion is required for the diagnosis of RAS in these instances so that timely revascularization can be undertaken to restore or preserve renal function and reduce the incidence of hospital admissions for heart failure syndromes. These are situations in which targeted early renal revascularization has a genuine chance of improving survival.