Introduction

Renal artery stenosis can be asymptomatic, but is also the root of a variety of syndromes caused by reduced blood perfusion to the kidney, such as renovascular hypertension and ischaemic nephropathy.[1–3] Over the past 15 years, clinical studies have suggested that medical therapy alone is equally effective to angioplasty in renal artery stenosis;[4–6] however, these studies included participants mostly on the basis of the anatomical presence of renal artery stenosis and not the presence of renal artery stenosis-associated renovascular hypertension or ischaemic nephropathy.[7] This crucial element could have led to misinterpretation of these findings by caregivers, depriving patients with renal artery stenosis-associated disease, and a clear indication for revascularization, of the procedure.

We present a case of successful revascularization of relapsing atherosclerotic renal disease, as a rescue therapy in a complex patient with previous endovascular abdominal aortic aneurysm repair (EVAR), solitary functioning kidney with progressive advanced chronic kidney disease (CKD) and uncontrolled multidrug-resistant secondary hypertension.

Case report

A 69-year-old man visited our outpatient clinic of hypertensive nephropathy for uncontrolled, multidrug-resistant, secondary hypertension. His home blood pressure (BP) had persisted in a range of 170–190/90–110 mmHg over the past few years, despite different drug combinations. Over the previous months he had been receiving long-acting nifedipine (30 mg × 2), carvedilol (12.5 mg × 2), doxazosin (4 mg × 2), clonidine (0.150 mg × 3) and furosemide (40 mg × 2) (Table 1).

His hypertension history started 10 years before this visit (in 2004), when evaluation revealed an abdominal aortic aneurysm, bilateral renal artery stenosis and CKD with an initial creatinine value of 194 μmol/l (Table 2a). He was initially treated with EVAR with suprarenal fixation, and simultaneous balloon angioplasty and stenting of the left renal artery. The patient also reported coronary heart disease treated with transdermal glyceryl trinitrate (5 mg × 1), diastolic heart failure, both diagnosed over the past 2 years, and hyperlipidaemia treated with atorvastatin (20 mg × 1) and fenofibrate (200 mg × 1). An episode of gastrointestinal bleeding 7 years ago due to multiple intestine angiodysplasiae was the reason for converting his antiplatelet clopidogrel treatment to dipyridamole (75 mg × 1). The patient was a heavy smoker, with an average of 40 cigarettes over the past 45 years.

Since receiving the diagnosis of CKD, the patient had undergone routine nephrology follow-up, with progressive deterioration of renal function. He presented a renal scintigraphy, performed 5 years ago, showing a glomerular filtration rate (GFR) calculated with the Gates method of 45 ml/min, distributed in favour of the left kidney (86%), with the right kidney appearing smaller with severely impaired blood flow and function. Renal ultrasound also suggested reduced size and cortical thinning of the right kidney, with simple cysts on both kidneys. The patient reported no follow-up of his EVAR with computed tomography (CT)–angiography, owing to his treating nephrologist fearing a deterioration in renal function.

On his first evaluation, the patient had a weight of 91 kg, height of 1.76 m and body mass index of 29.4 kg/m², with preserved muscle mass. Office BP was 174/96 mmHg and pulse rate 82 beats/min, without orthostatic hypotension. Examination of the heart revealed a systolic murmur, whereas lung auscultation was normal. The abdomen was tender with no evidence of hepatomegaly, splenomegaly or systolic bruits over the umbilicus. Peripheral pulses were normal but there was lower leg oedema. Neurological examination yielded normal findings. Standard laboratory tests revealed: haemoglobin 122 g/l, urea nitrogen 15.7 mmol/l, serum creatinine 274 μmol/l, sodium 139 mmol/l, potassium 4.1 mmol/l, calcium 2.15 mmol/l, phosphate 1.55 mmol/l, uric acid 256 μmol/l, cholesterol 5.9 mmol/l, triglycerides 1.42 mmol/l, high-density lipoprotein 1.27 mmol/l and low-density lipoprotein 4.0 mmol/l. These values reflected an estimated glomerular filtration rate (eGFR) of 21.3 ml/min/1.73 m², but 24 h urine collection showed creatinine clearance of 27.2 ml/min/1.73 m², urea clearance of 19.1 ml/min/1.73 m² and urine protein excretion of 0.49 g/24 h (Table 2). A new renal scintigraphy showed complete loss of perfusion of the right kidney and severe reduction of perfusion and function of the left kidney, with a calculated GFR of 14 ml/min. A triplex ultrasonography showed the treated aneurysm to be in a stable condition, and confirmed the absence of flow in the right kidney and reduced flow in the left kidney, but was unable to uncover the relapsed renal artery stenosis in the left kidney. An extensive consultation with the vascular surgeons resulted in focusing on BP reduction with modification of antihypertensive treatment, owing to the technical difficulties involved in any procedure, with repeat assessment in 4 months.

Over the following 2 months, careful adjustments were made to the patient’s antihypertensive treatment, aiming to gradually reduce BP. A renin–angiotensin system blocker was clearly contraindicated. Furosemide, nifedipine and carvedilol were increased to a total daily dose of 120 mg, 150 mg and 37.5 mg, respectively. He also started on tamsulosin (0.4 mg × 1), for symptoms of prostatic hyperplasia. Despite 24 h urine sodium at a level of 141 mmol/day, the patient received further counselling on additional careful sodium reduction. The patient also received counselling on smoking cessation and he drastically reduced his smoking to about 10 cigarettes/daily. These changes achieved a significant drop in the patient’s BP to a range of values 140–160/80–95 mmHg. However, over this period his kidney function slightly deteriorated, with creatinine and urea nitrogen levels of 336 μmol/l and 19.7 mmol/l, reflecting an eGFR of 16.9 ml/min/1.73 m². At 3 months, patient had further increases in serum creatinine to 442 μmol/l and urea nitrogen to 23 mmol/l. He was then admitted to our nephrology department, where no apparent cause of acute renal failure was noted and kidney function recovered to previous levels within 4 days (creatinine 282.9 μmol/l, urea nitrogen 18.3 mmol/l) only with a reduction of furosemide to 60 mg/day. During his admission the intake of all drugs was witnessed and ambulatory BP monitoring confirmed inadequate control of BP.

At the 4 month visit, the patient reported another hospitalization due to an acute ischaemic stroke, starting with the acute onset of hemiparesis, dysarthria and diplopia. A magnetic resonance imaging brain scan revealed multiple ischaemic lesions, and therapy with low-molecular-weight heparin and acetylsalicylic acid (100 mg × 1) was started. Triplex ultrasonography of the carotid arteries revealed 50% stenosis bilaterally. At 4 days, only diplopia persisted, which fully reversed within 20 days. His BP and renal function were unchanged during hospitalization. At his follow-up appointment, his home BP levels averaged 140–150/80–95 mmHg but his creatinine and urea nitrogen values reached 442 μmol/l and 23.7 mmol/l, respectively, reflecting an eGFR of 12.3 ml/min/1.73 m².

On this basis, we had a new consultation with the vascular surgery team and decided that an intervention coupled with three haemodialysis sessions to remove contrast media was justified as an attempt to rescue the renal function. The patient was fully informed and consented. Under local anaesthesia, an intraoperative angiography revealed relapse of the stenosis at the proximal left renal artery, where the previous stent had been placed (Figure 1). A renal double curve guiding catheter was inserted, after a challenging procedure, owing to the suprarenal fixation of the aortic endograft, which impeded the direct intraluminal access. A premounted balloon-expandable stent was deployed internally to the pre-existing one, and dilatations with balloons were performed before and after its placement. A non-tunnelled dual-lumen central venous catheter was also placed in the left femoral vein and three daily haemodialysis sessions were performed to reduce the risk of nephrotoxicity from the contrast medium.

Postoperatively, kidney function rapidly improved and creatinine levels dropped by 175 μmol/L within 24 h. Similarly, a significant improvement in BP occurred during the first day, with mean values of 120–150/80–90 mmHg coupled with orthostatic hypotension during the first 3 days, despite the interruption of furosemide, clonidine and doxazosin, and reduction of nifedipine and carvedilol to 60 mg and 25 mg per day, respectively (Table 1). Double antiplatelet therapy was started with acetylsalicylic acid (100 mg × 1) and clopidogrel (75 mg × 1). On the fourth postoperative day, the patient was transferred to our department for polyuria and adjustment of pharmacological therapy, as orthostatic hypotension persisted. At this point, creatinine (283 μmol/l) and urea nitrogen levels (15.8 mmol/l) remained stable without dialysis, reflecting an eGFR of 20.6 ml/min/1.73 m², while creatinine clearance was 36.5 ml/min/1.73 m². As expected, there was an increase in protein urine excretion, with a total amount of 4.4 g/24 h. The patient was discharged at 8 days postoperatively with stable renal function and BP levels of 120–130/70–80 mmHg with amlodipine (10 mg × 1) and carvedilol (12.5 mg × 2).

Approximately 7 months after his surgery, the patient’s renal function has further improved, with creatinine and urea nitrogen values of 265 μmol/l and 15 mmol/l, respectively (eGFR = 22.2 ml/min/1.73 m²). His BP remains well controlled with gradual additions of tamsulosin 0.4 mg and doxazosin 4 mg daily. His haemoglobin level is constant at 119 g/l, and no episodes of intestinal blood loss have been reported under the double antiplatelet therapy.

Discussion

Renal artery stenosis ranges from an asymptomatic presence to a variety of syndromes due to reduced renal blood flow beyond the level of autoregulatory compensation.[1] Renovascular hypertension is suggested to account for 30% of patients with secondary hypertension,[8] with atherosclerotic stenosis and fibromascular dysplasia representing 90% and 10% of cases, respectively.[9,10] In addition, atherosclerotic renal artery stenosis may lead to ischaemic renal disease with reduced renal mass, usually when luminal occlusion exceeds 70%; ischaemic nephropathy is currently a major health problem, estimated to affect 5–20% of patients older than 50 years with advanced CKD.[2,3] Bilateral atherosclerotic renal artery stenosis is not uncommon, with an occurrence ranging between 20% and 46% of patients with renal artery stenosis.[5,6]

Treatment of atherosclerotic renal artery stenosis and relevant complications has gained increased attention over the past 15 years. Following evidence from small studies,[4] large-scale randomized clinical trials have suggested that there is no significant improvement in renal function, mean BP and mortality by revascularization compared with medical therapy.[5,11,12] Apart from various confounders limiting interpretation, these studies suffer from important selection bias as they included subjects on the basis of the anatomical presence of renal artery stenosis (angiographical stenosis of >60%) and not solely patients with renal artery stenosis-associated disease (i.e. renovascular hypertension effectively proven with functional testing or progressive ischaemic nephropathy).[5–11] The inclusion of patients with asymptomatic renal artery stenosis may have considerably diluted the results.

Our patient’s history indicated ischaemic renal disease as the primary cause of CKD. It is noticeable that even though bilateral renal artery stenosis was known and resistant hypertension persisted, angioplasty of both renal arteries within a time-frame of some months was not considered. Furthermore, restenosis of atherosclerotic renal artery stenosis lesions after percutaneous renal angioplasty is an important problem, as 12–14% of patients may develop restenosis within 9 months to 2 years of follow-up.[13,14] Placement of a stent during angioplasty is suggested to reduce the restenosis rate,[14] but even so, patients should be monitored through BP and renal function measurements, as well as triplex ultrasonography every 3 months.[15] In this case, no consideration or repeat angioplasty took place, despite important deterioration of renal function and refractory hypertension. Another issue in this patient was abdominal aneurysm repair. Suprarenal stents are usually used for better fixation to abdominal aneurysms with short or complicated necks, although they seem to be equally effective to infrarenal fixation.[16,17] In addition, we have recently shown that patients with suprarenal grafts have a 13% lower eGFR in 12 months and a threefold decrease rated in 24 months, compared with infrarenal fixation.[18,19] This information should also be considered in such patients with important GFR decline.

From the patient’s first visit to our department, a vascular surgeon appointment was booked and the technical difficulties of a possible endovascular repair in a solitary kidney with previous artery stenting and reduced renal function, through an aorta with previous suprarenal EVAR, were extensively discussed. A decision was made to guide therapy based on BP control, after careful modifications of antihypertensive agents, based on available evidence.[5,11,12] Indeed, important BP reduction was achieved with careful changes and the patient’s informed consent and increased compliance. From a diagnostic point of view, we considered the diagnosis of relapsed left renal artery stenosis highly possible, but we opted not to check it with CT angiography owing to the high risk of renal function progression to end-stage renal disease. Magnetic resonance angiography was also not a preferred option because of the possibility of nephrogenic systemic fibrosis and the need for acute haemodialysis.

Despite the significant improvement in BP from practically small drug adjustments, within a few months of follow-up, our patient experienced an acute ischaemic stroke, i.e. a severe complication from one hypertension target organ. Moreover, his renal function progressively deteriorated towards end-stage renal disease and suggested that renal replacement therapy was an inevitable solution. Although the patient was relatively stable, without major complications of stage 5 CKD and preserved creatinine clearance, his renal function could have deteriorated from simple prerenal causes (e.g. a systolic BP drop to levels of 100–110 mmHg). At this point, the cost–benefit ratio was in favour of an intervention trial, with acute haemodialysis to remove constant media. Apart from the clear-cut benefit of immediate BP reduction and the decreased need for antihypertensive medications, an important delay in the need for renal replacement therapy may be possible, since the patient’s renal function has practically doubled and remains stable several months after the procedure.

In conclusion, recent evidence from studies including subjects with anatomical renal artery stenosis should not be extrapolated to patients with clear evidence of renal artery stenosis-associated complications, such as renovascular hypertension and/or ischaemic nephropathy. Revascularization is a routine procedure that should be offered without delay in specific individuals, as it may confer undisputed benefit towards BP control and preservation of renal function even in the most complex or seemingly hopeless cases, as in the case of our patient.

Disclosure statement

This paper was not supported by any source and represents an original effort by the authors. No potential conflict of interest was reported by the authors.