Renal & Urinary

Renal artery stenosis: workup and revascularization decisions

Clinical Overview and When to Suspect Renal Artery Stenosis

— Atherosclerotic RAS (ARAS): ~90% of cases. Older adults (>55), ostial/proximal lesions, coexists with CAD, PAD, carotid disease, smoking, dyslipidemia, diabetes.

— Fibromuscular dysplasia (FMD): ~10%. Women aged 15–50, mid-to-distal renal artery, classic "string of beads" on angiography. Also affects carotid/vertebral arteries.

— Onset of HTN before age 30 (think FMD) or severe HTN after age 55 (think ARAS)

— Resistant HTN: uncontrolled on ≥3 agents including a diuretic at optimal doses

— Accelerated, malignant, or hypertensive emergency presentation

— Acute, unexplained rise in creatinine ≥30% within 1 week of starting an ACEi or ARB

— Unexplained azotemia in an older patient with diffuse atherosclerosis

— Recurrent flash pulmonary edema with preserved LV function ("Pickering syndrome")

— Asymmetric kidney size (>1.5 cm difference) on imaging

— Abdominal or flank bruit

Board pearl: A 68-year-old smoker with PAD whose creatinine jumps from 1.2 → 1.9 three days after lisinopril is started has bilateral RAS until proven otherwise — stop the ACEi and image the renal arteries.

Step 3 management: Do not screen asymptomatic patients with well-controlled HTN; screening is justified only when a clinical clue is present AND revascularization would be considered if positive.

Definition: Hemodynamically significant narrowing (>60–70%) of one or both renal arteries, reducing perfusion pressure and activating the renin-angiotensin-aldosterone system (RAAS), producing renovascular hypertension and/or ischemic nephropathy.

Two dominant etiologies in the US:

When to suspect — the AHA/ACC "clinical clues":

Pathophysiology pearl: Unilateral RAS → ischemic kidney secretes renin → angiotensin II–mediated HTN; the contralateral kidney undergoes pressure natriuresis. Bilateral RAS (or RAS to a solitary kidney) → both kidneys volume-retain → volume-dependent HTN with flash pulmonary edema and ACEi-induced AKI.

Presentation Patterns and Key History

— BP uncontrolled despite ACEi/ARB + CCB + thiazide at maximal tolerated doses with confirmed adherence

— May present as hypertensive urgency/emergency, especially in older atherosclerotic patients or young women with FMD

— Recurrent, sudden-onset pulmonary edema, often nocturnal, with preserved ejection fraction

— Classically bilateral ARAS; sodium/volume retention plus surge HTN drives diastolic failure

— Strong indication for revascularization

— Creatinine rises >30% within days to weeks of initiating or up-titrating RAAS blockade

— Suggests bilateral RAS or unilateral RAS in a solitary functioning kidney

— Loss of efferent arteriolar tone → drop in GFR

— Ischemic nephropathy: slowly rising creatinine, minimal proteinuria (<1 g/d), benign urinalysis, asymmetric kidneys

— Age at HTN onset, trajectory, medication adherence (verify with pharmacy refill data)

— Smoking, dyslipidemia, diabetes, family history of premature CV disease

— Episodes of acute dyspnea or pulmonary edema; OSA screening (resistant HTN mimic)

— NSAID, decongestant, licorice, or stimulant use (secondary HTN mimics)

— In young women: headache, pulsatile tinnitus, neck pain, prior carotid dissection → FMD clues

— Prior imaging showing kidney size discrepancy

Key distinction: Primary aldosteronism causes resistant HTN with hypokalemia and suppressed renin; RAS causes resistant HTN with high renin and often normal-to-low potassium from secondary hyperaldosteronism. The aldosterone:renin ratio differentiates them.

Board pearl: A 32-year-old woman with new HTN, headaches, and a cervical bruit — get an MRA from the circle of Willis through the renal arteries; FMD is a pan-arterial disease.

Pattern 1 — Resistant or accelerated HTN:

Pattern 2 — Flash pulmonary edema (Pickering syndrome):

Pattern 3 — ACEi/ARB-induced AKI:

Pattern 4 — Progressive CKD with bland sediment:

Pattern 5 — Incidental finding on CT/MRA done for other indication.

Key history questions:

Physical Exam Findings and Hemodynamic Assessment

— Confirm HTN with proper technique: appropriate cuff size, supported arm at heart level, after 5 min of rest, both arms initially

— Out-of-office BP (home or 24-hour ambulatory) is essential before labeling "resistant" — rule out white-coat HTN (~30% of "resistant" cases)

— Orthostatic vitals: significant orthostasis on multiple antihypertensives may limit therapy

— Abdominal bruit: systolic-diastolic (continuous) epigastric or flank bruit is ~40% sensitive but ~99% specific for RAS

— Carotid, femoral, and pedal pulse exam: diminished pulses or bruits suggest diffuse atherosclerosis (ARAS likely)

— S4 gallop, LV heave from hypertensive heart disease

— Signs of volume overload: JVD, rales, peripheral edema — particularly after flash pulmonary edema episode

— Retinal exam: hypertensive retinopathy (AV nicking, hemorrhages, exudates, papilledema in emergency)

— Cutaneous: xanthomas, tendinous xanthelasma → dyslipidemia/atherosclerosis

— Neurologic deficits suggest prior stroke or carotid FMD (in young patients)

— Asymmetric BP between arms >15 mmHg → consider subclavian stenosis or large-vessel disease

— Wide pulse pressure suggests stiff arteries (ARAS context)

— Hypertensive crisis with end-organ damage (encephalopathy, ACS, dissection) mandates parenteral therapy and ICU admission

Step 3 management: Before workup for secondary HTN, confirm true resistance: (1) accurate measurement technique, (2) out-of-office BP, (3) adherence verification, (4) optimal triple therapy including a thiazide-like diuretic (chlorthalidone) at adequate dose.

Board pearl: A continuous flank bruit in a young woman with new HTN is essentially pathognomonic for FMD — proceed directly to CTA or MRA of the renal arteries.

Vital signs:

Cardiovascular exam:

Other relevant findings:

Hemodynamic clues to severity:

Diagnostic Workup — Initial Labs and Imaging

— BMP: creatinine, eGFR, potassium, bicarbonate (low K+ → think aldosteronism; high K+ may limit ACEi use)

— UA with microscopy and spot albumin/creatinine ratio: bland sediment with mild proteinuria favors ischemic nephropathy

— Plasma aldosterone-to-renin ratio (ARR): in RAS, both renin and aldosterone are elevated → ARR typically <20; in primary aldosteronism, ARR >20–30 with suppressed renin

— TSH, fasting glucose, lipid panel, plasma metanephrines if pheochromocytoma suspected

— Drug screen if stimulant abuse suspected

— Duplex renal ultrasound: non-invasive, no contrast, no radiation; preferred in CKD (eGFR <30) and pregnancy. Peak systolic velocity >180–200 cm/s and renal-aortic ratio >3.5 suggest stenosis >60%. Resistive index >0.8 predicts poor response to revascularization. Operator-dependent; limited by body habitus and bowel gas.

— CT angiography (CTA): excellent spatial resolution, fast; requires iodinated contrast — avoid in eGFR <30 unless necessary. Preferred when ultrasound is non-diagnostic and renal function is adequate.

— MR angiography (MRA) with gadolinium: avoids iodinated contrast and radiation; avoid gadolinium if eGFR <30 (nephrogenic systemic fibrosis risk, though lower with newer agents). Tends to overestimate stenosis severity.

Step 3 management: In an older patient with diffuse atherosclerosis and eGFR 25, start with duplex ultrasound — it avoids both iodinated contrast and gadolinium while still answering the clinical question.

Board pearl: Captopril renography has been largely abandoned due to poor performance in bilateral disease and CKD; do not pick it on the exam unless explicitly framed as a historical option.

Initial labs (every resistant HTN workup):

First-line imaging — choose based on patient factors:

ECG and echo: assess for LVH, diastolic dysfunction, prior MI — relevant for cardiovascular risk and for the flash pulmonary edema phenotype.

Diagnostic Workup — Advanced and Confirmatory Studies

— Gold standard for anatomic diagnosis

— Reserved for patients in whom revascularization is being actively considered, because of contrast load, radiation, and procedural risks (dissection, atheroembolism, AKI, access-site complications)

— Allows simultaneous measurement of translesional pressure gradient — a peak systolic gradient >20 mmHg or mean gradient >10 mmHg confirms hemodynamic significance

— In FMD, shows the classic "string of beads" appearance in the mid-distal renal artery

— Fractional flow reserve (FFR) and resting Pd/Pa ratios are emerging tools to confirm hemodynamic significance and avoid stenting anatomically tight but functionally insignificant lesions

— Renal vein renin sampling: largely historical; poor predictive value for revascularization outcomes

— In suspected FMD: image the entire vascular tree at least once — head/neck CTA or MRA — because of high prevalence of cerebrovascular FMD and intracranial aneurysms (~10–15%)

— Screen for aortic aneurysm in older atherosclerotic patients with RAS (shared risk factors)

— Baseline creatinine and eGFR within 30 days

— Cardiac risk stratification per ACC/AHA perioperative guidelines if functional capacity is poor

— Hold metformin around iodinated contrast if eGFR <30 or AKI; hydrate with isotonic saline; minimize contrast volume

Key distinction: Anatomic stenosis ≠ hemodynamic significance. A 60% lesion without a pressure gradient or velocity acceleration usually does not justify intervention. Modern practice prioritizes physiology + clinical syndrome over the angiographic image alone.

CCS pearl: Before ordering catheter angiography, document the clinical syndrome that would change management with revascularization (flash pulmonary edema, true resistant HTN, ACEi-induced AKI) — otherwise the test is not indicated.

Catheter-based digital subtraction angiography (DSA):

Functional/physiologic adjuncts during angiography:

Imaging for associated disease:

Pre-procedural assessment:

Risk Stratification and First-Line Management Logic

— BP control to <130/80 mmHg (ACC/AHA 2017), with RAAS blockade as cornerstone unless contraindicated

— High-intensity statin (atorvastatin 40–80 or rosuvastatin 20–40)

— Antiplatelet therapy: aspirin 81 mg daily

— Smoking cessation, weight loss, sodium restriction (<2.3 g/day), DASH diet, exercise

— Glycemic control if diabetic (A1c individualized, generally <7%)

— Recurrent flash pulmonary edema

— Refractory HTN despite ≥3 maximally tolerated drugs including a diuretic, with documented adherence

— Rapidly progressive CKD attributable to RAS, especially bilateral

— Hemodynamically significant RAS in a solitary functioning kidney with declining function

— Intolerance to medical therapy (e.g., recurrent ACEi-induced AKI in bilateral disease)

Step 3 management: A 70-year-old with 75% ARAS, BP 138/82 on lisinopril + amlodipine + chlorthalidone, eGFR 55 and stable → continue OMT; do not stent. Adding revascularization will not improve outcomes and adds procedural risk.

Board pearl: CORAL was negative — memorize it. The exam will test the urge to "fix what's broken" anatomically.

Core clinical principle (CORAL trial, 2014): In stable atherosclerotic RAS with controlled HTN and stable renal function, optimal medical therapy (OMT) is non-inferior to renal artery stenting for the composite of death, MI, stroke, hospitalization for CHF, progressive renal insufficiency, and need for renal replacement therapy.

Therefore, the first-line strategy for most ARAS is OMT, not intervention. Stenting is reserved for specific high-yield clinical syndromes.

OMT pillars:

Indications to escalate to revascularization (atherosclerotic RAS):

For FMD: Lower threshold for revascularization (percutaneous transluminal angioplasty without stenting) — younger patients, longer life expectancy, durable response, often curative for HTN if treated early.

Pharmacotherapy — First-Line Drug Regimen

— In unilateral RAS: ACEi/ARB lowers BP effectively; the contralateral healthy kidney maintains overall GFR. Generally well tolerated.

— In bilateral RAS or RAS to a solitary kidney: ACEi/ARB can precipitate AKI by dropping efferent arteriolar tone. Start low, monitor creatinine and potassium at 1–2 weeks. A creatinine rise up to ~30% with stable potassium can be acceptable; >30% rise or hyperkalemia → stop and reassess (consider revascularization).

— Examples: lisinopril 10–40 mg daily, losartan 50–100 mg daily; switch to ARB for ACEi cough.

— High-intensity statin regardless of LDL: atherosclerotic vascular disease equivalent

— Aspirin 81 mg for established atherosclerosis

— Smoking cessation counseling and pharmacotherapy (varenicline or NRT)

Key distinction: Do not withhold ACEi/ARB from a patient with unilateral RAS — that is the standard of care. The contraindication is bilateral RAS or RAS to a solitary kidney where renal function deteriorates with RAAS blockade.

Step 3 management: Monitor BMP within 1–2 weeks of starting or up-titrating any ACEi/ARB in a patient with known or suspected RAS; document creatinine and potassium response.

RAAS blockade (ACEi or ARB) is first-line even in RAS:

Add a thiazide-like diuretic: chlorthalidone 12.5–25 mg or indapamide; preferred over HCTZ for resistant HTN due to longer half-life and stronger evidence. Switch to loop diuretic (furosemide, torsemide) if eGFR <30.

Add a long-acting dihydropyridine CCB: amlodipine 5–10 mg daily.

Fourth agent for resistant HTN: spironolactone 25–50 mg daily (PATHWAY-2 trial evidence) — particularly effective; monitor potassium, especially with concurrent ACEi/ARB and CKD.

Additional agents: beta-blocker (esp. with CAD or CHF), hydralazine, minoxidil, central alpha-agonists (clonidine — beware rebound HTN).

Adjunctive secondary prevention:

Procedures — Revascularization Decisions and Technique

— Percutaneous transluminal renal angioplasty (PTRA) with stenting — standard for atherosclerotic ostial lesions (elastic recoil makes plain angioplasty inadequate)

— PTRA without stenting (balloon angioplasty alone) — preferred for FMD; durable, often curative

— Surgical revascularization (aortorenal bypass, endarterectomy) — reserved for complex anatomy, failed endovascular attempts, or concomitant aortic surgery

— Recurrent flash pulmonary edema with significant bilateral stenosis (or unilateral with solitary kidney)

— Truly resistant HTN despite optimized 4-drug regimen including a mineralocorticoid antagonist

— Progressive CKD attributable to RAS (especially bilateral, rapid trajectory)

— Acute renal artery occlusion/dissection (emergent)

— Hypertension with FMD and reasonable life expectancy — angioplasty offers high cure or improvement rates

— Even modest BP gains are valuable given decades of expected exposure

— Hold ACEi/ARB and diuretics morning of procedure; hold metformin per institutional protocol

— IV isotonic saline pre/post for contrast nephropathy prophylaxis; minimize contrast volume

— Dual antiplatelet therapy (aspirin + clopidogrel) typically initiated before stenting and continued ≥4 weeks (often longer); lifelong aspirin

— Statin pretreatment may reduce contrast AKI and periprocedural events

— Atheroembolism ("blue toe," livedo, eosinophilia, worsening renal function 1–4 weeks post)

— Renal artery dissection, perforation, thrombosis

— Access-site hematoma, retroperitoneal bleed

— Contrast-induced AKI

— In-stent restenosis (long-term)

Step 3 management: Use a distal embolic protection device when feasible during ARAS stenting to reduce atheroembolic AKI. Continue OMT post-procedure — stenting does not replace statins, antiplatelets, or BP control.

Board pearl: New-onset livedo reticularis and eosinophilia 2 weeks after renal stenting = cholesterol embolization syndrome; supportive care, continue statin, no role for steroids or anticoagulation.

Modalities:

Indications for revascularization (ARAS):

Indications (FMD):

Pre-procedure preparation:

Procedural complications:

Special Populations — Elderly and Renal/Hepatic Impairment

— Disproportionate prevalence of ARAS; often incidental on imaging for other indications

— Weigh procedural risk against limited life expectancy and competing risks (frailty, dementia, falls)

— BP target: ACC/AHA <130/80 if tolerated; SPRINT data support intensive control in ambulatory, non-frail older adults, but individualize for orthostasis, falls, and polypharmacy

— Start antihypertensives at lower doses; avoid abrupt titration; review for orthostasis at each visit

— De-prescribe when appropriate; reassess number of agents annually

— Iodinated contrast: prefer ultrasound or non-contrast MRA when eGFR <30; if CTA is essential, use low-osmolar/iso-osmolar contrast at minimum volume, IV isotonic saline pre/post

— Gadolinium-based MRA: avoid group I agents in eGFR <30; newer macrocyclic agents (group II) are considered low-risk but still use cautiously

— Hyperkalemia management: dietary K+ restriction, loop diuretic, patiromer or sodium zirconium cyclosilicate to enable ACEi/ARB continuation

— Adjust dosing: many antihypertensives need no adjustment; renally cleared drugs (atenolol, certain ARBs) require dose review

— Less relevant directly to RAS but affects drug choice: avoid methyldopa in active liver disease; caution with hepatically metabolized agents (losartan, carvedilol)

— RAAS blockade remains preferred for renoprotection and albuminuria reduction

— Add SGLT2 inhibitor for CKD with albuminuria — additive renoprotection; monitor for euglycemic DKA and volume status

Step 3 management: In an 82-year-old with ARAS, eGFR 32, and BP 142/78 on three agents — prioritize fall risk assessment, home BP monitoring, and tolerability over aggressive titration; avoid contrast-based confirmatory imaging unless revascularization would be pursued.

Board pearl: Frailty trumps trial protocol — SPRINT excluded nursing home residents and patients with diabetes or prior stroke.

Elderly (≥75 years):

CKD (any cause, including ischemic nephropathy):

Hepatic impairment:

Diabetes:

Special Populations — Pregnancy, FMD, and Younger Patients

— ACEi, ARBs, direct renin inhibitors, and spironolactone are contraindicated in pregnancy (teratogenic: oligohydramnios, renal dysgenesis, skull hypoplasia, fetal hypotension)

— Preferred agents: labetalol, nifedipine ER, methyldopa, hydralazine

— Suspected RAS in pregnancy: duplex ultrasound is first-line; avoid CT and gadolinium MR; non-contrast MRA can be considered after first trimester if essential

— Severe RAS-related HTN in pregnancy: multidisciplinary management; revascularization is generally deferred; rare emergent angioplasty has been performed

— Counsel women of reproductive age with RAS on contraception and pre-conception medication review; switch off RAAS blockade before conception

— Predominantly women 15–50, often presents with HTN at young age

— Screen all FMD patients with one-time head-to-pelvis vascular imaging (CTA or MRA) for cerebrovascular FMD, aneurysms, and dissections (US Registry for FMD recommendation)

— Antiplatelet therapy (aspirin 81 mg) typically recommended for stroke prevention

— Angioplasty without stenting is the procedural treatment of choice; cure rates of HTN highest when treated early

— Avoid renal artery stenting in FMD unless angioplasty fails or causes dissection

— RAS is a leading cause of secondary HTN in children (along with coarctation)

— Consider midaortic syndrome, neurofibromatosis type 1, Williams syndrome, Takayasu arteritis

— Diagnostic imaging: ultrasound first; angiography in specialized pediatric center

— Refer to pediatric nephrology/cardiology

Key distinction: FMD = angioplasty alone, no stent. ARAS = stent the ostial lesion when intervention is indicated. Mixing these up is a classic exam trap.

Board pearl: A pregnant woman on lisinopril with new RAS-related HTN — stop lisinopril immediately and switch to labetalol or nifedipine ER; counsel on teratogenicity.

Pregnancy:

Fibromuscular dysplasia (FMD):

Pediatrics:

Complications and Adverse Outcomes

— LVH and diastolic dysfunction → flash pulmonary edema

— Hypertensive emergencies: encephalopathy, hemorrhagic stroke, aortic dissection, MI, malignant nephrosclerosis

— Hypertensive retinopathy with hemorrhages, exudates, papilledema

— Progressive bilateral renal atrophy → CKD → ESRD requiring dialysis

— Often paucisymptomatic until late; bland sediment, minimal proteinuria, asymmetric kidneys

— MI, stroke, peripheral artery disease, heart failure

— Patients with ARAS have higher all-cause and cardiovascular mortality than matched HTN controls — independent of revascularization

— Cholesterol embolization syndrome: livedo, blue toes, eosinophilia, AKI 1–6 weeks post; no specific treatment; statins continued, supportive care

— Contrast-induced AKI: typically peaks at 48–72 hours; usually reversible

— Renal artery dissection, perforation, thrombosis → emergent surgical or endovascular salvage

— In-stent restenosis: 15–25% within 1–2 years; managed with repeat angioplasty ± drug-coated balloon

— Access-site complications: hematoma, pseudoaneurysm, retroperitoneal bleed

— ACEi/ARB-induced AKI in undiagnosed bilateral RAS

— Hyperkalemia (especially with spironolactone + ACEi/ARB + CKD)

— Cough, angioedema (ACEi); ARB substitution

Step 3 management: Suspect cholesterol embolization in any patient with worsening renal function, new livedo reticularis, and peripheral eosinophilia 1–4 weeks after any aortic instrumentation — no specific antidote, but discontinue anticoagulation if possible and optimize statin therapy.

Board pearl: Hypocomplementemia and eosinophiluria can also accompany cholesterol embolization, mimicking interstitial nephritis or vasculitis — history of recent catheterization clinches the diagnosis.

Hypertensive end-organ damage:

Ischemic nephropathy:

Cardiovascular events (driven by shared atherosclerotic burden):

Procedural complications (after PTRA/stenting):

Medication-related complications:

When to Escalate Care — ICU, Consult, Inpatient Triage

— Hypertensive emergency: BP severely elevated with acute end-organ damage (encephalopathy, ICH, aortic dissection, ACS, acute pulmonary edema, eclampsia, acute kidney injury)

— Initiate IV antihypertensives: labetalol, nicardipine, clevidipine (preferred for most); nitroprusside (caution with cyanide toxicity, especially CKD); esmolol; phentolamine (catecholamine excess)

— Target: reduce MAP by ≤25% in the first hour, then to 160/100 over the next 2–6 hours, then gradually to goal over 24–48 hours — except aortic dissection (rapid to SBP <120) and acute ischemic stroke (permissive HTN unless thrombolysis planned)

— Severe HTN without end-organ damage but with concerning trajectory or unreliable outpatient follow-up

— Flash pulmonary edema episode for diuresis, volume reassessment, and expedited RAS workup

— Acute renal artery occlusion (sudden flank pain, anuria if bilateral, LDH elevation) → emergent vascular surgery/IR consultation; revascularization within hours preserves function

— Nephrology: progressive CKD, complex BP management, electrolyte issues, dialysis planning

— Interventional radiology or vascular surgery: procedural candidates

— Cardiology: comorbid CAD, heart failure, perioperative risk

— Hypertension specialist: truly resistant cases or rare secondary etiologies

— Stable HTN with confirmed RAS on OMT → follow in primary care + nephrology every 3–6 months

CCS pearl: For hypertensive emergency, order continuous BP monitoring (arterial line preferred), IV antihypertensive, BMP, troponin, ECG, CXR, urinalysis, head CT (if neuro symptoms), then admit to ICU. Do not aim to normalize BP within minutes — controlled descent prevents watershed strokes.

Step 3 management: Acute renal artery occlusion is a time-sensitive emergency; revascularization within 3–6 hours can salvage renal function.

ICU admission indications:

Inpatient (non-ICU) admission:

Consultations:

Outpatient pathway (most patients):

Key Differentials — Same-Category Causes of Secondary HTN

— Resistant HTN, often with spontaneous or diuretic-induced hypokalemia

— Plasma aldosterone/renin ratio (ARR) >20–30 with elevated aldosterone (>15 ng/dL) and suppressed renin

— Confirmatory: saline infusion, oral salt loading, or captopril challenge

— Adrenal CT and adrenal vein sampling (≥35 years) to distinguish unilateral adenoma from bilateral hyperplasia

— Treatment: laparoscopic adrenalectomy (unilateral) vs. spironolactone/eplerenone (bilateral)

— Episodic HTN, palpitations, headaches, diaphoresis; orthostasis

— Plasma free metanephrines or 24-hour urinary fractionated metanephrines

— Imaging: CT/MRI adrenals; MIBG or DOTATATE for extra-adrenal

— Pre-op: alpha blockade (phenoxybenzamine) before beta blockade

— Young patient with HTN, arm-leg BP gradient, radiofemoral delay, rib notching on CXR

— Echo and CTA/MRA confirm; surgical or endovascular repair

Key distinction: RAS = high renin, high aldosterone (secondary hyperaldosteronism); primary aldosteronism = low renin, high aldosterone (primary). The ARR is the single most useful screening test to separate them.

Board pearl: Three "secondary HTN" findings on the exam should always trigger workup: (1) resistant HTN, (2) early-onset (<30) or late-onset (>55) severe HTN, (3) HTN with hypokalemia not explained by diuretics — order ARR first.

Primary aldosteronism:

Pheochromocytoma/paraganglioma:

Cushing syndrome: weight gain, central obesity, striae, hyperglycemia; 1 mg overnight dexamethasone suppression or 24-h urinary cortisol screening.

Coarctation of the aorta:

Thyroid dysfunction: hyperthyroidism → systolic HTN with wide pulse pressure; hypothyroidism → diastolic HTN.

Acromegaly, hyperparathyroidism, congenital adrenal hyperplasia: less common but appear on differentials.

Key Differentials — Other-Category Causes of the Clinical Syndrome

— Acute decompensated heart failure (HFrEF or HFpEF) — get echo; BNP

— Acute coronary syndrome with ischemic mitral regurgitation

— Hypertensive emergency without RAS

— Diastolic dysfunction with sodium load (NSAIDs, dietary indiscretion)

— Volume depletion (diuretic overuse, GI losses)

— Concurrent NSAID use

— Sepsis, contrast nephropathy

— Decompensated heart failure with cardiorenal syndrome

— Hypertensive nephrosclerosis: bilateral small kidneys, long-standing HTN, modest proteinuria

— Diabetic nephropathy: typically larger kidneys early, significant albuminuria

— Atheroembolic disease (cholesterol emboli): subacute AKI, livedo, eosinophilia, recent catheterization

— Obstructive uropathy: hydronephrosis on ultrasound

— Chronic interstitial nephritis (chronic NSAID use, lithium)

— Pseudoresistance: poor technique, white-coat effect, non-adherence (the single most common cause)

— Obstructive sleep apnea — screen with STOP-Bang, polysomnography

— Alcohol >2 drinks/day; cocaine, amphetamines, ephedra

— NSAIDs, oral contraceptives, glucocorticoids, calcineurin inhibitors, VEGF inhibitors, SNRIs, decongestants, licorice

— Chronic kidney disease itself

Key distinction: Pseudoresistance is far more common than true resistant HTN. Confirm adherence (pill counts, pharmacy refills, witnessed dosing) and out-of-office BP before initiating an expensive workup for secondary causes.

Board pearl: A patient with "resistant HTN" whose snoring keeps the partner awake — screen for OSA before chasing RAS.

Mimics of flash pulmonary edema:

Mimics of ACEi-induced AKI rise in creatinine:

Mimics of ischemic nephropathy:

Mimics of resistant HTN:

Vasculitis (Takayasu arteritis): young women, large-vessel inflammation, can involve renal arteries — elevated ESR/CRP, characteristic imaging, may mimic FMD.

Secondary Prevention and Long-Term Plan

— High-intensity statin: atorvastatin 40–80 mg or rosuvastatin 20–40 mg; LDL goal <70 mg/dL given established ASCVD

— Consider ezetimibe and PCSK9 inhibitor if LDL remains above goal

— Antiplatelet therapy: aspirin 81 mg daily; dual antiplatelet (aspirin + clopidogrel) for ≥4 weeks (often longer per operator) post-renal stenting

— Smoking cessation: counseling at every visit, varenicline or NRT; document quit attempts

— <130/80 mmHg per ACC/AHA 2017 for most adults with ASCVD and/or CKD

— Home BP monitoring with validated cuff; teach proper technique; goal of average ≥12 morning and evening readings/week

— Continue ACEi/ARB if tolerated (essential in proteinuric CKD)

— Add SGLT2 inhibitor in CKD with eGFR ≥20 (especially with albuminuria) — DAPA-CKD, EMPA-KIDNEY data; benefit independent of diabetes

— Bicarbonate replacement if metabolic acidosis (HCO3 <22) — slows CKD progression

— Avoid nephrotoxins: NSAIDs, iodinated contrast when possible, aminoglycosides

— Aspirin + clopidogrel + statin + ACEi/ARB (titrated) + appropriate add-ons

— Explicit teaching on each medication, side effects, and when to call

Step 3 management: After renal artery stenting, the most important long-term interventions are lipid lowering, antiplatelet therapy, BP control, and smoking cessation — not stent surveillance imaging.

Board pearl: Many exam questions test that revascularization does not replace OMT; it adds to it.

Atherosclerotic risk factor modification (the highest-yield intervention):

Blood pressure target:

Renoprotection:

Glycemic and lipid co-management: A1c individualized (<7% for most); coordinate with diabetes care.

Vaccinations: influenza annually, pneumococcal series, COVID-19, RSV (age-appropriate), zoster — CKD patients are functionally immunocompromised.

Discharge medication reconciliation after revascularization:

Follow-Up, Monitoring, and Counseling

— Office visit at 2–4 weeks: review BP log, medication tolerance, wound/access site, signs of cholesterol embolization

— BMP at 1–2 weeks (creatinine, K+), then 1–3 months, then every 6 months

— Duplex ultrasound surveillance at 1, 6, 12 months, then annually to screen for in-stent restenosis

— Continue medical therapy lifelong

— Every 1–3 months until BP at goal, then every 3–6 months

— Lipid panel at 4–12 weeks after statin start/change, then annually

— Annual UACR and eGFR; sooner if rapid changes

— Annual diabetic retinal exam if applicable

— Home BP twice daily for 1 week prior to each visit; bring log

— Daily weights if heart failure component or flash pulmonary edema history

— Symptom diary: chest pain, dyspnea, leg swelling, episodes of vision changes or headache

— Sodium <2.3 g/day (ideally <1.5 g/day)

— Potassium-rich diet (only if eGFR adequate and no hyperkalemia)

— Alcohol ≤1 drink/day (women), ≤2 drinks/day (men)

— 150 min/week moderate aerobic exercise + 2 days resistance training

— Weight loss if BMI ≥25 (every 1 kg ≈ 1 mmHg BP drop)

— Stress reduction, sleep hygiene, OSA treatment if present

Step 3 management: Order surveillance duplex ultrasound — not CTA — for stent patency; it avoids contrast and radiation in a CKD-prone population.

Board pearl: Persistent or recurrent HTN after renal stenting should prompt duplex evaluation for in-stent restenosis and re-screening for missed secondary causes (e.g., aldosteronism, OSA).

Post-revascularization follow-up cadence:

Medical management follow-up (no procedure):

Home monitoring:

Lifestyle counseling (DASH framework):

Cardiac rehab: consider referral after procedural intervention or in patients with concurrent ASCVD.

Ethical, Legal, and Patient Safety Considerations

— Disclose specific risks: contrast nephropathy, atheroembolism, dissection, access-site bleeding, and the CORAL-era reality that stenting may not improve hard outcomes in stable ARAS

— Document discussion of alternatives, including continued medical therapy

— Use teach-back to confirm comprehension; provide written materials at appropriate health literacy

— Especially relevant in elderly or frail patients where procedural risk approaches benefit

— Use decision aids; discuss patient values (quality vs. quantity of life, willingness to take more pills vs. undergo procedure)

— Hospital-to-home: medication reconciliation is the single highest-risk step; a held ACEi must be explicitly restarted or formally discontinued with rationale documented

— Communicate with PCP within 7 days of discharge after procedure (CMS quality measure)

— Schedule follow-up labs before discharge, not "in a few weeks" verbally

— Hypertensive crisis with loss of consciousness or visual disturbance — assess driving safety; state-specific reporting requirements vary

— Suspected substance use contributing to resistant HTN — document, offer treatment referral; protect confidentiality except where mandated

— RAAS blockers, statins, and amlodipine are generic and inexpensive — prefer when clinically equivalent

— Address structural barriers: pharmacy access, transportation, food insecurity (low-sodium diet requires resources)

— Use 90-day fills, mail-order, and combination pills to improve adherence

Step 3 management: Always document why an ACEi/ARB was held during admission for AKI — and the explicit plan to either restart at discharge with monitoring or discontinue permanently. Failure to restart guideline-directed therapy is a leading transition-of-care safety failure.

Board pearl: Polypharmacy itself is a fall risk in older patients — reconcile medications at every visit.

Informed consent for renal angiography/stenting:

Shared decision-making:

Transition-of-care safety:

Mandatory reporting and legal items:

Health equity and access:

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: Memorize the four classic indications for revascularization: flash pulmonary edema, truly resistant HTN, rapidly progressive CKD, and FMD-related HTN. Everything else is medical therapy.

Key distinction: ARAS = stent ostium; FMD = balloon only, no stent.

CORAL trial (NEJM 2014): Renal artery stenting + OMT was not superior to OMT alone for cardiovascular and renal outcomes in stable ARAS. Drives modern conservative management.

ASTRAL trial (NEJM 2009): Similar negative result in atherosclerotic RAS.

Pickering syndrome: Recurrent flash pulmonary edema + bilateral RAS = strong indication for revascularization.

FMD "string of beads": Mid-distal renal artery, women 15–50, angioplasty without stent.

Renal artery resistive index >0.8 on duplex predicts poor BP and renal response to revascularization — argues for medical management.

Translesional gradient >20 mmHg peak or >10 mmHg mean = hemodynamically significant stenosis.

Creatinine rise >30% after ACEi initiation = suspect bilateral RAS.

Kidney size difference >1.5 cm on ultrasound is a classic RAS clue.

Aldosterone:renin ratio >20 with high aldosterone = primary aldosteronism; both elevated = RAS (secondary).

Cholesterol embolization: livedo, blue toes, eosinophilia, hypocomplementemia, AKI weeks after catheterization.

FMD screening: one-time head-to-pelvis CTA/MRA — high yield for cerebrovascular involvement and aneurysms.

Antihypertensives safe in pregnancy: labetalol, nifedipine ER, methyldopa, hydralazine. Contraindicated: ACEi, ARB, direct renin inhibitor, spironolactone.

Hypertensive emergency: lower MAP ≤25% in first hour; exceptions are aortic dissection (rapid to SBP <120) and ischemic stroke (permissive).

Spironolactone (PATHWAY-2): most effective 4th-line agent for resistant HTN.

Renal artery in Takayasu arteritis: consider in young patient with HTN + elevated inflammatory markers + large-vessel imaging changes.

Board Question Stem Patterns

— 68-year-old smoker, BP 168/96, started lisinopril 1 week ago; creatinine 1.1 → 1.9, K+ 5.2

— Best next step: Stop lisinopril and obtain renal duplex ultrasound

— Trap answers: continue lisinopril (wrong — >30% rise); start ARB (same mechanism); renal biopsy (premature)

— 72-year-old with recurrent nocturnal dyspnea, BP 195/110, EF 60%, bilateral renal artery stenosis 80%

— Best step: Refer for renal revascularization (Pickering syndrome — class indication)

— 34-year-old woman, BP 162/98, abdominal bruit, normal labs; renal angiography shows "string of beads"

— Best step: Percutaneous transluminal angioplasty without stent; also image head/neck vasculature

— 58-year-old on lisinopril, amlodipine, chlorthalidone with BP 152/94; adherence confirmed; ARR shows aldosterone 25, renin 0.3 (suppressed)

— Best step: Confirmatory saline suppression for primary aldosteronism — not RAS workup

— 70-year-old, 2 weeks after renal artery stenting; new livedo on legs, creatinine rising, eosinophils 8%

— Diagnosis: Cholesterol embolization syndrome; management is supportive (statin, BP control); avoid anticoagulation

— 71-year-old with incidental 70% unilateral RAS, BP 128/76 on two agents, eGFR 58, stable

— Best step: Continue optimal medical therapy; do not stent (CORAL)

— 28-year-old, 8 weeks pregnant, on lisinopril for HTN with known FMD

— Best step: Stop lisinopril, start labetalol or nifedipine ER

Board pearl: When asked "best next step" in suspected RAS with adequate renal function, the answer is usually duplex ultrasound — non-invasive, no contrast, no radiation.

Step 3 management: Match the indication to the right action: stable disease → OMT; specific syndromes → revascularize; pregnancy → swap to safe agents.

Stem 1 — "Creatinine bumped after ACEi":

Stem 2 — "Flash pulmonary edema, normal EF":

Stem 3 — "Young woman with HTN":

Stem 4 — "Resistant HTN":

Stem 5 — "Post-stent livedo and AKI":

Stem 6 — "Stable ARAS, well-controlled HTN":

Stem 7 — "Pregnant on ACEi":

One-Line Recap

Renal artery stenosis is a clinical-syndrome diagnosis: identify clues (resistant HTN, flash pulmonary edema, ACEi-induced AKI, asymmetric kidneys, young women with bruits), confirm with duplex ultrasound or CTA/MRA, treat most atherosclerotic disease with optimal medical therapy per CORAL, and reserve revascularization for flash pulmonary edema, truly resistant HTN, progressive ischemic nephropathy, or FMD — where angioplasty without stenting is curative.

Board pearl: The CORAL trial defines modern practice — anatomic stenosis alone does not justify intervention. Match the syndrome to the procedure.

Key distinction: ARAS = stent + lifelong OMT; FMD = balloon only + image the rest of the vascular tree; pregnancy = labetalol/nifedipine/methyldopa, never ACEi/ARB.

Step 3 management: Document the specific clinical clue and the specific clinical question being asked before ordering any imaging — RAS is a syndromic, not radiographic, diagnosis.

Workup logic: duplex ultrasound first (especially in CKD/pregnancy); CTA if function permits; catheter angiography only when revascularization is planned. Confirm hemodynamic significance with a translesional gradient before stenting.

Medical therapy is first-line for ARAS: ACEi/ARB (with monitoring) + thiazide-like diuretic + dihydropyridine CCB + spironolactone for resistance, plus high-intensity statin, aspirin, smoking cessation, and BP target <130/80.

Revascularize when: recurrent flash pulmonary edema (Pickering), refractory HTN despite 4-drug therapy with adherence confirmed, rapidly progressive CKD attributable to RAS, RAS in a solitary functioning kidney with declining function, or FMD with HTN. Stent ostial atherosclerotic lesions; angioplasty alone for FMD.

Always exclude mimics: pseudoresistance (non-adherence, white coat, poor technique), OSA, primary aldosteronism (ARR), pheochromocytoma, NSAIDs/decongestants, alcohol — these are far more common than RAS in "resistant HTN."