Renal artery stenosis and ischaemic nephropathy

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Renal hypoperfusion activates the renin-angiotensin-aldosterone system, raising systemic vascular resistance and sodium retention. In unilateral disease the other kidney can often excrete the extra sodium, so filtration may remain stable. With bilateral severe stenosis or a solitary functioning kidney, both pressure-dependent filtration and volume control can fail. Chronic hypoxia, atheroembolism and parenchymal loss then contribute to ischaemic nephropathy, a clinical syndrome rather than an imaging label.

Atherosclerotic renal-artery stenosis travels with coronary, cerebrovascular and peripheral arterial disease. The main benefit for many patients comes from blood-pressure control, lipid lowering, smoking cessation and treatment of CKD and diabetes. Large randomised trials did not support indiscriminate renal-artery stenting in stable disease, and the procedure carries contrast, access-site, cholesterol-embolisation, dissection and restenosis risks.

Assessment therefore asks two questions in sequence: is renovascular disease sufficiently plausible to justify arterial imaging, and is there a high-risk, potentially reversible phenotype if a severe lesion is found? Local renal-vascular MDT review is essential before invasive angiography or intervention, particularly when the kidney is small or scarred and physiological benefit is unlikely.

Key points

Most renal-artery stenosis in older adults is ostial atherosclerotic disease; fibromuscular dysplasia more often affects younger women and the mid-to-distal artery, and is considered separately.
Suspect a renovascular contribution when hypertension is genuinely resistant, starts abruptly or worsens unexpectedly, accompanies an abdominal bruit, or coexists with asymmetrical kidney size, widespread atherosclerosis or otherwise unexplained kidney decline.
A creatinine rise of 30% or more, or eGFR fall of 25% or more, after starting or increasing an ACE inhibitor or ARB should prompt repeat testing and a search for depletion, NSAIDs and renovascular disease rather than an automatic lifelong drug-allergy label.
Bilateral severe disease, or stenosis supplying a solitary functioning kidney, is the pattern most associated with salt retention, rapid loss of filtration and flash pulmonary oedema.
Duplex ultrasound is a useful first-line anatomical and haemodynamic test when performed by an experienced vascular laboratory; an inconclusive scan does not exclude a technically difficult ostial or branch lesion.
CT angiography usually gives the clearest arterial map, while contrast-enhanced or non-contrast MR angiography may be selected when iodinated contrast or radiation is problematic; modality choice belongs with renal and radiology teams.
An imaging stenosis is not by itself proof that hypertension or CKD is caused by that lesion. Correlate severity, kidney viability, clinical trajectory and the physiological phenotype.
For most atherosclerotic stenoses with stable kidney function and controlled blood pressure, optimal medical therapy and surveillance are preferred because routine stenting has not improved major renal or cardiovascular outcomes.
Revascularisation is an expert-MDT decision for selected high-risk presentations, including recurrent flash pulmonary oedema, truly resistant hypertension with severe stenosis, or severe functional decline while the supplied kidney remains viable.
Treat the whole vascular patient: confirm smoking status, blood pressure, lipids, diabetes, albuminuria and antithrombotic indication instead of focusing solely on the angiographic percentage.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Atherosclerotic renal artery disease

Calcified ostial plaque is the common pattern in older adults with smoking, diabetes or widespread vascular disease and may affect both kidneys.

Fibromuscular dysplasia

A non-atherosclerotic, non-inflammatory arteriopathy more often affects younger women and mid-distal renal arteries, producing focal narrowing or multifocal beading.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Reduced renal perfusion pressure
A haemodynamically important stenosis lowers pressure beyond the lesion and is sensed by the juxtaglomerular apparatus.
2
Renin-mediated hypertension
Renin–angiotensin activation increases vasoconstriction, aldosterone and sodium retention, sustaining hypertension and sometimes episodic or flash pulmonary congestion.
3
Filtration dependence on efferent tone
In bilateral severe disease or a solitary supplied kidney, filtration may depend on angiotensin-mediated efferent constriction and fall when that support changes.
4
Chronic ischaemic nephropathy
Sustained underperfusion causes parenchymal loss and kidney shrinkage, eventually limiting reversibility even if arterial patency is restored.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Atherosclerotic phenotype

An older smoker or patient with diabetes, coronary, carotid or peripheral arterial disease develops difficult hypertension, an epigastric or flank bruit, falling eGFR or unequal kidney sizes. Absence of a bruit does not rule disease out.

True resistant hypertension

Blood pressure remains above the agreed target despite confirmed adherence to optimal tolerated doses of at least three complementary agents, after excluding white-coat effect, measurement error, excess salt and interfering medicines.

RAAS-blockade signalRed flag

Kidney function deteriorates substantially soon after ACE-inhibitor or ARB initiation or dose escalation, particularly with little albuminuria, no obvious hypovolaemia and bilateral disease or a solitary kidney on imaging.

Cardiac destabilisation syndromeRed flag

Sudden pulmonary oedema recurs with severe hypertension and acute kidney injury, sometimes despite preserved left-ventricular systolic function. Bilateral haemodynamically important disease is a key, treatable possibility.

Ischaemic nephropathy

Progressive non-proteinuric or modestly proteinuric CKD occurs with vascular risk and a shrinking kidney. Marked albuminuria, active urine sediment or systemic inflammation should redirect attention towards parenchymal disease.

Incidental stable stenosis

Cross-sectional imaging finds a renal ostial lesion in a patient whose blood pressure and kidney function are stable. This common scenario usually calls for risk-factor treatment, not automatic catheter angiography or stenting.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Standardised clinic and out-of-office blood pressureFirst step
Why
Confirm severity and distinguish sustained resistance from technique, adherence or white-coat effects.
Interpretation and limitations
Use appropriate cuff size, standing measurements where indicated and ABPM or HBPM. Review dispensing, doses, salt, liquorice, NSAIDs, sympathomimetics and other causes before declaring treatment failure.
02
Serial creatinine, eGFR, potassium and urine ACR
Why
Define functional trajectory, treatment safety and the likelihood of competing renal parenchymal disease.
Interpretation and limitations
Retrieve pre-illness and pre-RAAS-blockade values. A large early haemodynamic fall merits prompt reassessment; heavy albuminuria or haematuria is less typical of isolated ischaemic nephropathy and requires parallel renal evaluation.
03
Renal-artery duplex ultrasound
Why
Screen arterial velocities, waveforms, renal-aortic ratio, kidney size and intrarenal resistance without contrast or radiation.
Interpretation and limitations
Results are operator- and patient-dependent. A high peak systolic velocity, raised renal-aortic ratio or distal tardus-parvus waveform supports stenosis, but local validated laboratory criteria should determine grading.
04
CT or MR angiography
Why
Confirm location, severity, accessory vessels, aortic disease and anatomy relevant to possible treatment.
Interpretation and limitations
CTA offers high spatial resolution but uses iodine and radiation. MRA avoids radiation but has device, motion and contrast limitations; radiology should tailor technique to eGFR and the clinical question.
05
Cardiac and systemic vascular assessment
Why
Identify heart failure physiology and the wider atherosclerotic burden that drives prognosis.
Interpretation and limitations
ECG, echocardiography, lipid profile, HbA1c and symptom-directed coronary, carotid or limb assessment can alter both acute management and prevention, even when the renal lesion is not revascularised.
06
Catheter angiography with physiological assessment
Why
Define a lesion immediately before an intervention when non-invasive anatomy and clinical benefit have been agreed by an MDT.
Interpretation and limitations
It is invasive and not a routine diagnostic screening test. Pressure gradients, parenchymal viability and procedural feasibility are interpreted together; visual percentage alone can overstate functional importance.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Primary hypertension

Common essential hypertension lacks abrupt onset, a convincing stenotic phenotype or asymmetric renal consequences, and an incidental lesion may not be causal.

Renal parenchymal disease

Albuminuria, active sediment or bilateral intrinsic abnormalities suggest glomerular or tubulointerstitial disease as the main driver of hypertension and reduced filtration.

Apparent treatment resistance

Incorrect cuff technique, white-coat effect, non-adherence, high salt intake or interfering medicines can mimic resistant renovascular hypertension and should be resolved before causal imaging.

Congestive cardiorenal disease

Primary cardiac dysfunction and venous congestion can cause flash pulmonary oedema and AKI without renal artery stenosis; cardiac and vascular imaging clarify contribution.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Flash oedemaStabilise and expose the renovascular phenotypeFirst stepAbrupt pulmonary oedema with severe hypertension, acute kidney injury or recurrent unexplained episodes.

1Treat oxygenation, ventilation, blood pressure and congestion through the acute heart-failure pathway, obtain ECG and urgent biochemistry, and avoid an indiscriminate fluid challenge.
2Review prior kidney function, RAAS-blocker exposure and cardiac imaging; request urgent renal-artery imaging if bilateral disease or a solitary functioning kidney is plausible.
3Discuss the case during the same admission with renal, vascular and interventional specialists because selected bilateral atherosclerotic lesions may justify revascularisation once the patient is stabilised.

02Stable suspicionConfirm before imagingDifficult hypertension, progressive CKD, a bruit or asymmetric kidneys without acute organ injury.

1Validate blood-pressure technique and adherence, reconcile medicines, quantify ACR and chart eGFR so common pseudo-resistance and intrinsic kidney disease are not missed.
2Use experienced-laboratory duplex first where suitable, progressing to CTA or MRA when suspicion remains high, the scan is indeterminate or intervention planning requires an arterial map.
3If disease is stable, institute medical prevention and planned renal/BP surveillance; refer severe lesions with high-risk clinical features to a renal-vascular MDT rather than arranging routine stenting.

03Creatinine riseRespond safely to RAAS inhibitionCreatinine rises at least 30% or eGFR falls at least 25% after ACE-inhibitor or ARB initiation or titration.

1Repeat creatinine and potassium promptly, assess blood pressure and volume, and look for NSAIDs, diuretics, sepsis, urinary obstruction and other reversible causes.
2Temporarily reduce or stop the implicated agent when guideline thresholds persist while correcting reversible factors; manage dangerous hyperkalaemia or hypotension immediately.
3AlternativeSeek renal advice and investigate for renovascular disease when no alternative explains the change, then make any cautious reintroduction decision against the original cardio-renal indication.

04MDT selectionRevascularise a patient, not an imageSevere stenosis coexists with recurrent pulmonary oedema, verified resistant hypertension or major kidney decline.

1Confirm lesion severity and haemodynamic relevance, exclude competing causes and assess whether the supplied kidney has useful size, cortex and recoverable function.
2Balance expected BP, fluid-control or renal benefit against contrast injury, embolisation, dissection, restenosis and the patient's frailty, bleeding risk and treatment goals.
3When benefit is credible, agree angioplasty and usually stenting for atherosclerotic ostial disease in an experienced service, with a documented post-procedure antithrombotic and surveillance plan.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

Controls hypertension and may protect proteinuric kidney and cardiovascular disease despite renovascular disease not being an absolute contraindication.

ACE inhibitor or angiotensin-receptor blocker

Choose and titrate a licensed preparation to the highest tolerated dose under the indication-specific formulary.

Check creatinine and potassium before treatment and usually within one to two weeks after starting or increasing; use particular caution in bilateral severe stenosis, a solitary kidney, hypovolaemia, hyperkalaemia or concurrent NSAID use.

Achieves sustained blood-pressure control when RAAS blockade is insufficient, temporarily unsuitable or not tolerated.

Amlodipine and complementary antihypertensives

Amlodipine commonly starts at 5 mg once daily, then is titrated within its licence; combine according to NICE sequencing.

Confirm adherence and postural tolerance before escalation; ankle oedema may confuse volume assessment, while beta-blockers, diuretics and alpha-blockers each require indication, electrolyte and comorbidity review.

Reduces the systemic atherosclerotic risk that usually determines outcome in atheromatous renovascular disease.

Atorvastatin

Use 20 mg once daily for eligible CKD primary prevention, or the NICE secondary-prevention intensity where established cardiovascular disease applies.

Check interactions, baseline liver profile and unexplained muscle symptoms; dose and intensity should follow NICE lipid guidance rather than the renal stenosis percentage alone.

Provides secondary vascular prevention when atherosclerotic renal-artery disease or another established arterial indication justifies it.

Single antiplatelet therapy

Aspirin 75 mg once daily or clopidogrel 75 mg once daily may be selected under vascular policy.

Do not add antiplatelet therapy mechanically to anticoagulation; assess gastrointestinal and intracranial bleeding, allergy, planned procedures and whether the finding represents clinical atherosclerotic disease.

May restore perfusion in carefully selected high-risk atherosclerotic disease with a viable kidney and a reversible clinical syndrome.

Percutaneous renal-artery angioplasty and stenting

A procedural strategy selected and delivered by an experienced renal-vascular service after multidisciplinary review, not a drug dose.

Routine intervention in controlled stable disease is not indicated; consent must cover arterial injury, atheroembolism, contrast-associated harm, access bleeding, restenosis and failure to improve pressure or filtration.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Resistant hypertension

Persistent renin activation can sustain severe hypertension despite multiple medicines, increasing risks of stroke, myocardial injury and further renal damage.

Progressive ischaemic nephropathy

Bilateral severe disease or stenosis to a solitary functioning kidney can reduce viable renal mass and cause declining filtration.

Flash pulmonary oedema

Sudden sodium retention and afterload elevation can cause recurrent rapid pulmonary congestion, particularly with bilateral severe renovascular disease.

Acute haemodynamic decline

Volume loss, NSAIDs or altered renin–angiotensin tone may sharply reduce filtration in a kidney dependent on compensatory arteriolar constriction.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record home or ambulatory blood-pressure trends and standing symptoms after each treatment change; a single clinic value cannot establish resistant hypertension or procedural success.
Check creatinine and potassium before RAAS blockade and after initiation or dose increase, acting on the percentage change from a verified baseline rather than a laboratory flag alone.
Follow eGFR slope, urine ACR and kidney size over time. Accelerated decline, recurrent oedema or a new drug-related haemodynamic fall should trigger earlier renal reassessment.
After intervention, follow the treating centre's schedule for duplex patency, restenosis, renal function, blood pressure and antithrombotic review; do not discontinue medicines merely because the artery was treated.
Audit smoking status, diabetes control, lipids, antiplatelet or anticoagulant indication and symptoms of coronary, cerebral and limb ischaemia as part of each vascular review.
Safety-net sudden breathlessness, rapidly falling urine output, severe headache or neurological deficit and uncontrolled pressure with chest pain or confusion for emergency assessment.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Stenosis is not causation

A common incidental ostial plaque can coexist with essential hypertension. Clinical response is most plausible when lesion severity, pressure physiology and a high-risk syndrome align.

The contralateral kidney matters

One healthy kidney can preserve sodium balance in unilateral disease; this explains why bilateral stenosis and solitary-kidney disease cause a more dramatic cardiorenal presentation.

Creatinine change is proportional

The useful signal after RAAS blockade is the percentage rise from baseline plus potassium and haemodynamic context, not whether creatinine has crossed the local reference range.

Low protein does not mean low risk

Ischaemic nephropathy may have relatively modest albuminuria, yet the associated diffuse atherosclerotic burden confers substantial cardiovascular risk requiring active prevention.

Viability limits benefit

Reopening an artery supplying a small scarred kidney is unlikely to restore meaningful filtration, so parenchymal size and cortex enter the intervention decision.

Trials changed routine practice

ASTRAL and CORAL support medical treatment for stable atherosclerotic disease; they do not remove expert consideration for under-represented flash-oedema or rapidly deteriorating phenotypes.

11Common pitfallsFrequent interpretation and management errors.

01
Calling hypertension resistant before checking cuff technique, adherence, home readings, salt intake and interfering medicines.
02
Diagnosing ischaemic nephropathy from an incidental CT stenosis without charting kidney function, ACR and alternative renal causes.
03
Withholding every ACE inhibitor permanently in unilateral disease even when there is a strong cardiac or proteinuric indication and monitoring is feasible.
04
Continuing RAAS blockade unchanged through a persistent threshold kidney-function fall, hypotension or dangerous hyperkalaemia without urgent review.
05
Referring all anatomical lesions for stenting despite stable filtration and controlled pressure.
06
Assuming a technically successful procedure has cured systemic atherosclerosis or removed the need for prevention and follow-up.