Key Facts

RAS is an important but often over-treated cause of secondary hypertension. The ASTRAL and CORAL trials changed practice, demonstrating that most atherosclerotic RAS should be managed medically.

Epidemiology

• Atherosclerotic RAS: found in 7% of patients >65 years at autopsy; 15-30% of patients with peripheral vascular disease
• FMD: much rarer; predominantly young women
• Prevalence increases with age and cardiovascular risk factors

Aetiology

• Atherosclerosis (90%): ostial/proximal stenosis; associated with generalised atherosclerosis
• FMD (10%): medial fibroplasia (most common subtype); mid/distal renal artery; "string-of-beads" appearance
• Other rare causes: Takayasu arteritis, neurofibromatosis, radiation, aortic dissection

Pathophysiology

• Stenosis reduces renal perfusion → activation of RAAS
• Increased renin → angiotensin II → aldosterone → sodium/water retention → hypertension
• Chronic ischaemia → ischaemic nephropathy → renal atrophy
• GFR maintained by angiotensin II-mediated efferent arteriolar vasoconstriction → ACEi/ARB removes this compensation → AKI
• Bilateral RAS or RAS in solitary kidney: severe renal impairment

Hypertension

• Resistant hypertension: uncontrolled on 3+ antihypertensives
• Severe/accelerated hypertension: particularly if onset age >55 or <30
• Abrupt onset of hypertension in previously normotensive patient

Renal

• AKI precipitated by ACEi/ARBs: >20-30% rise in creatinine
• Asymmetric kidney size (>1.5cm difference on USS)
• Progressive CKD despite good BP control

Cardiovascular

• Flash pulmonary oedema: bilateral RAS; recurrent sudden-onset APO
• Abdominal bruit: heard in 40-50% (epigastric/flank)
• Generalised atherosclerosis: peripheral vascular disease, coronary artery disease, carotid disease

Red Flags

• Flash pulmonary oedema → bilateral RAS
• AKI on ACEi → stop and investigate
• Young woman with severe hypertension → FMD

Bloods

• U&Es: creatinine (may be elevated), potassium (hypokalaemia suggests secondary hyperaldosteronism)
• Lipid profile: cardiovascular risk
• Plasma renin and aldosterone: elevated renin (but not routinely measured)

Imaging

• Duplex renal ultrasound: first-line screening; peak systolic velocity >180cm/s suggests >60% stenosis; resistance index >0.8
• MR angiography (gadolinium-enhanced): gold standard non-invasive; 90-95% sensitivity/specificity
• CT angiography: alternative if MRI contraindicated; excellent for atherosclerotic disease
• Catheter angiography: gold standard but invasive; reserved for intervention
• Captopril renography: functional test; sensitivity ~90% for unilateral RAS; less used now

Special Tests

• Renal USS: asymmetric kidney size (>1.5cm difference suggests significant RAS on the smaller side)
• 24h ambulatory BP: confirm resistant hypertension

Medical Management (First-Line for Atherosclerotic RAS)

• Antihypertensives: calcium channel blocker (amlodipine) + thiazide-like diuretic (indapamide) first-line
• ACEi/ARB: can be used cautiously for unilateral RAS (monitor creatinine/K+ at 1-2 weeks); contraindicated in bilateral RAS or single kidney with RAS
• Statin: atorvastatin 80mg for cardiovascular risk reduction
• Antiplatelet: aspirin 75mg or clopidogrel
• Smoking cessation: essential

Revascularisation

Atherosclerotic RAS:

• ASTRAL (2009) and CORAL (2014) trials: stenting provided no additional benefit over medical therapy for BP control or renal function preservation
• Stenting reserved for: flash pulmonary oedema, rapidly declining renal function despite medical therapy, failure of medical BP control, or recurrent AKI

Fibromuscular dysplasia:

• Percutaneous transluminal angioplasty (PTA) without stenting: curative in 60-80%
• First-line treatment for FMD
• Screen for FMD in other vascular beds (carotid, iliac)

Referral Criteria

• Suspected RAS → nephrology/vascular
• FMD → specialist vascular centre
• Flash pulmonary oedema with suspected bilateral RAS → urgent referral

• Atherosclerotic RAS: progressive; 10-20% of stenoses progress to occlusion over 5 years
• Medical therapy: adequate BP control achieved in 70-80% with multi-drug regimen
• FMD after angioplasty: cure of hypertension in 30-50%, improvement in 30-40%
• Ischaemic nephropathy: progressive CKD despite treatment in many patients with bilateral disease
• Cardiovascular events: leading cause of death in atherosclerotic RAS patients

Atherosclerotic RAS vs FMD

ASTRAL and CORAL Trials