Renal Artery Stenosis

Renal artery stenosis is narrowing of the main renal artery or its branches, causing reduced renal perfusion, activation of the renin angiotensin aldosterone system, and renovascular hypertension and ischaemic nephropathy.

Causes

• Atherosclerosis (about 90%): older patients, usually ostial or proximal third of the main artery, often bilateral, with coexisting coronary, carotid or peripheral arterial disease. Present in 6 to 7% of people over 65, and up to 25 to 30% of those with coronary or peripheral arterial disease.
• Fibromuscular dysplasia (about 10%): young to middle-aged women, mid and distal artery and branches, with a string of beads appearance.
• Others: Takayasu arteritis, aortic dissection, neurofibromatosis type 1, radiation, polyarteritis nodosa, thromboembolism, trauma, and transplant renal artery stenosis.

Haemodynamically significant stenosis is generally 70% or more by diameter, or 50 to 70% with a translesional gradient.

Pathophysiology

• Reduced perfusion pressure stimulates renin release, with angiotensin II-mediated vasoconstriction and aldosterone-induced sodium retention.
• Unilateral stenosis with a normal contralateral kidney (two kidney, one clip model) causes renin-dependent hypertension, with pressure natriuresis in the opposite kidney and often hypokalaemia.
• Bilateral stenosis or stenosis to a solitary kidney causes volume-dependent hypertension and is susceptible to flash pulmonary oedema.
• Angiotensin II maintains glomerular filtration through efferent arteriolar constriction. ACE inhibitors and ARBs remove this and may precipitate acute kidney injury.
• Chronic ischaemia produces atrophy, parenchymal fibrosis, and ischaemic nephropathy.

Natural history: progression of atherosclerotic stenosis occurs in 10 to 20% over 3 years, and total occlusion in a minority. Renal function and survival are determined chiefly by cardiovascular comorbidity.

Clinical clues to renovascular hypertension

• Resistant hypertension (uncontrolled on three agents including a diuretic).
• Abrupt onset of hypertension before 30 years (suggesting fibromuscular dysplasia) or after 55 years.
• Sudden worsening of previously stable hypertension, accelerated or malignant hypertension.
• Recurrent flash pulmonary oedema or refractory heart failure with preserved ejection fraction (Pickering syndrome).
• Unexplained renal impairment, or a rise in creatinine of more than 30% within 2 weeks of starting an ACE inhibitor or ARB.
• Unequal kidney sizes (a difference of more than 1.5 cm) on imaging.
• Hypokalaemia with raised renin and aldosterone.
• Epigastric or flank systolic-diastolic bruit (heard in about 40% of cases), and evidence of atherosclerosis elsewhere.

Fibromuscular dysplasia features

• Headache, pulsatile tinnitus, neck bruit, spontaneous arterial dissection (carotid, vertebral, coronary), aneurysm.

Differential diagnosis

• Essential hypertension, primary aldosteronism, phaeochromocytoma, coarctation, renal parenchymal disease, obstructive sleep apnoea, drug-induced hypertension (NSAIDs, decongestants, oral contraceptives), and chronic kidney disease.
• Flash pulmonary oedema should also prompt consideration of ischaemic heart disease and valvular disease.

Screen when the clinical probability is high and a revascularisation decision would follow.

Laboratory tests

• Creatinine and eGFR, electrolytes (hypokalaemia), urinalysis (bland sediment, proteinuria usually under 1 g/day), plasma renin and aldosterone with aldosterone to renin ratio to exclude primary aldosteronism.
• BNP in heart failure presentations.

Imaging

• Renal duplex ultrasound is the first test (sensitivity and specificity of 85 to 95% in experienced hands):
• Peak systolic velocity above 180 to 200 cm/s indicates 60% or greater stenosis.
• Renal to aortic velocity ratio above 3.5 indicates a significant lesion.
• Tardus parvus waveform in the intrarenal arteries with an acceleration time over 0.07 seconds.
• Resistive index above 0.80 predicts poor response to revascularisation.
• Kidney length below 8 cm suggests irreversible atrophy.
• CT angiography has 95% sensitivity and specificity. Accompanies contrast risk in renal impairment.
• MR angiography with gadolinium (use group II agents, gadobutrol 0.1 mmol/kg, with caution when eGFR is below 30) or non-contrast techniques. It overestimates stenosis.
• Catheter angiography is the reference standard. A translesional systolic pressure gradient above 20 mmHg, or a distal to aortic pressure ratio below 0.9, indicates a haemodynamically significant lesion.
• Captopril renography is no longer favoured because of low sensitivity in chronic kidney disease.

Evaluate for atherosclerosis at other sites, and screen young women with fibromuscular dysplasia with imaging of the head, neck and pelvis for dissections and aneurysms.

Medical therapy (all patients)

• Blood pressure target below 130/80 mmHg.
• ACE inhibitors or ARBs are effective and renoprotective in unilateral disease: ramipril 2.5 mg daily titrated to 10 mg, or losartan 25 mg daily titrated to 100 mg. Check creatinine and potassium at 1 to 2 weeks after starting and after each dose change. Accept a rise of up to 30%, and stop if it is exceeded or hyperkalaemia occurs.
• Use with great caution in bilateral stenosis or stenosis in a solitary kidney.
• Add amlodipine 5 to 10 mg daily, a thiazide-like diuretic (chlorthalidone 12.5 to 25 mg daily, or furosemide 40 to 80 mg in eGFR below 30), and a beta blocker (bisoprolol 2.5 to 10 mg daily) as needed.
• Statin (atorvastatin 40 to 80 mg daily), aspirin 75 to 100 mg daily, smoking cessation and glycaemic control.
• Randomised trials show that renal artery stenting added to optimal medical therapy does not improve blood pressure, renal function or cardiovascular events in most patients with stable atherosclerotic disease.

Indications for revascularisation

• Recurrent flash pulmonary oedema or refractory heart failure with bilateral stenosis or a solitary functioning kidney.
• Resistant hypertension with preserved renal size and haemodynamically significant stenosis despite maximum medical therapy.
• Rapidly progressive loss of renal function with bilateral stenosis or stenosis to a solitary kidney, and an acute kidney injury precipitated by ACE inhibitor or ARB.
• Fibromuscular dysplasia with hypertension.
• Transplant renal artery stenosis with hypertension or graft dysfunction.

Techniques

• Fibromuscular dysplasia: percutaneous balloon angioplasty alone, without stent, which gives cure or marked improvement of hypertension in about 60 to 80%. Stent for dissection or recoil.
• Atherosclerotic ostial disease: angioplasty with balloon-expandable stent. Dual antiplatelet therapy (aspirin 75 to 100 mg with clopidogrel 75 mg) for 1 month then aspirin alone. Use embolic protection in selected patients. Restenosis occurs in 10 to 30%.
• Surgical revascularisation (aortorenal bypass with saphenous vein, splenorenal or hepatorenal bypass, endarterectomy, ex vivo repair with autotransplantation) for complex branch lesions, failed endovascular treatment, or concurrent aortic surgery.
• Nephrectomy of a small, non-functioning kidney (under 7 to 8 cm with minimal function on renography) causing refractory hypertension.

Contrast and procedural precautions

• IV isotonic saline 1 mL/kg/h for 6 to 12 hours before and after contrast in eGFR below 30, minimise contrast volume, and hold nephrotoxins.
• Complications include dissection, perforation, cholesterol embolism, contrast nephropathy and access site injury.

Follow-up

• Duplex at 1, 6 and 12 months after intervention, then annually. Monitor blood pressure, creatinine, potassium and the number of antihypertensive agents. Cardiovascular risk reduction continues lifelong.