Renal artery stenosis

Renal artery stenosis is the narrowing of one or both renal arteries. It is most commonly caused by atherosclerosis. In young women, fibromuscular dysplasia is an important underlying cause. Decreased renal blood flow due to renal artery stenosis causes activation of the renin-angiotensin-aldosterone system, which in turn results in secondary hypertension. Physical examination may reveal an abdominal bruit. Patients with progressive renal artery stenosis may develop renal insufficiency and renal atrophy. Duplex ultrasonography and/or angiography are used for screening and to confirm the diagnosis. Treatment of renal artery stenosis primarily consists of antihypertensive therapy, including ACE inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers, or beta blockers. Antihypertensive therapy may need to be continued indefinitely. Patients on ACE inhibitors or ARBs should be closely monitored for an increase in serum creatinine, especially if they have bilateral renal artery stenosis. Patients with hemodynamically significant renal artery stenosis may require revascularization. Treatment of the underlying cause is essential to prevent disease progression.

• Accounts for 1–10% of all hypertension cases ^[1]
• 3–10% of pediatric cases of secondary hypertension have a renovascular etiology. ^[2]
• Age and sex preponderance depend on the underlying cause (see “Etiology” below).

Epidemiological data refers to the US, unless otherwise specified.

• Atherosclerosis (∼ 90% of cases): occurs more often in men > 50 years of age; increased risk in smokers ^[3]
• Fibromuscular dysplasia (∼ 10% of cases): mostly affects women < 50 years of age
• Other causes (∼ 1%) ^[3]
  • Improper surgical anastomosis after renal transplantation
  • Vasculitis (e.g., Takayasu arteritis, polyarteritis nodosa, Kawasaki disease)
  • Hereditary conditions (e.g., neurofibromatosis type 1)
  • Extrinsic compression (e.g., abdominal aortic aneurysm, retroperitoneal tumors)
  • Abdominal radiation therapy

• Narrowing of one or both renal arteries → obstruction of renal blood flow → ischemia → renin release and activation of the renin-angiotensin-aldosterone system → hyperreninemic hyperaldosteronism (increased renin → increased angiotensin → increased aldosterone) → increased sodium retention and peripheral vascular resistance → renovascular hypertension (secondary hypertension) ^[4]
• Prolonged renal hypoperfusion → chronic stimulation of the juxtaglomerular apparatus to secrete renin → hyperplasia of the juxtaglomerular apparatus ^[5][6][7]
• No improvement in renal blood flow → ischemic renal injury → renal insufficiency and progressive renal atrophy (unilateral or bilateral depending on laterality of RAS) ^[3]

• Family history of hypertension is often absent.
• Hypertension: severe (i.e., resistant to therapy) and/or early-onset (i.e, hypertension in individuals < 30 years of age) ^[3][8]
• Abdominal bruit heard over the flank or epigastrium: present during both systole and diastole ^[9]
• Flash pulmonary edema
• Features of atherosclerosis in other parts of the body (e.g., peripheral artery disease, coronary artery disease, carotid stenosis)
• Features of renal insufficiency (e.g., nausea, edema)

Imaging is required to confirm a clinical suspicion of renal artery stenosis. Laboratory findings may provide supportive evidence but are not diagnostic.

Imaging ^[8][10]

Indications

A high pretest probability for renal artery stenosis, as determined by the presence of ≥ 1 of the following features. ^[8]

• Onset of hypertension before the age of 30 years
• Severe hypertension after the age of 55 years
• Hypertension resistant to a 3-drug antihypertensive regimen (resistant HTN)
• New-onset or worsening of renal dysfunction (↑ serum creatinine) after initiating ACE inhibitors or ARBs
  • ACE inhibitors and ARBs can induce or worsen renal insufficiency, particularly in patients with severe bilateral renal artery stenosis or high-grade unilateral stenosis. ^[11]
• Acute worsening of previously controlled hypertension
• Hypertension with acute end-organ damage (hypertensive emergency)
• Unexplained renal atrophy or asymmetry of > 1.5 cm between the kidneys
• Unexplained acute pulmonary edema

Modalities ^[8][10][11]

The choice of modality depends on the presence and severity of renal dysfunction. Consider a nephrology and/or radiology consult in patients with significant renal dysfunction (eGFR < 30 mL/min/1.73 m²) to help guide this decision.

• First-line (screening) tests
  • Renal dysfunction present: duplex ultrasonography (US) or MR angiography without contrast
  • Normal or near-normal renal function: duplex US, CT angiography, or MR angiography with gadolinium contrast
• Second-line test: catheter angiography (diagnostic gold standard) ^[12]
  • Consider if the index of suspicion for renal artery stenosis is high despite inconclusive noninvasive imaging
  • Disadvantages
    • Invasive modality associated with procedural complications, including radiation exposure
    • Risk of contrast-induced nephropathy
• Additional imaging (not recommended for establishing a diagnosis) ^[10]
  • Consider captopril renal scintigraphy to assess renal function.
  • Renal vein renin measurement can help lateralize the most affected kidney (the ischemic kidney secretes higher levels of renin compared to the normal or less affected kidney).

In patients with renal dysfunction, there is a risk of contrast-induced nephropathy with CT/catheter angiography and a risk of nephrogenic systemic fibrosis with MR angiography with gadolinium contrast.

Findings

• Increased systolic flow velocity in the renal artery (on duplex US) ^[10]
• Segmental narrowing of one or both renal arteries
  • Stenotic segment(s) can be complete or partial and solitary or multiple.
  • Hemodynamically significant renal artery stenosis ^[13][14]
    • ≥ 70% narrowing of the renal artery diameter on imaging
    • Or a 50–69% narrowing of the renal artery diameter with evidence of increased renal arterial pressures, such as:
      • Translesional systolic pressure gradient of ≥ 20 mm Hg
      • Mean pressure gradient ≥ 10 mm Hg
• The site of renal artery stenosis differs according to the underlying etiology.
  • Proximal 1/3^rd: typically due to atherosclerotic disease ^[15]
  • Distal 2/3^rds with stenotic segments alternating with aneurysms (“string of beads” appearance): typically seen in fibromuscular dysplasia ^[16]
• Ipsilateral renal atrophy (decrease in kidney size) ^[15]

Patients with hemodynamically significant renal artery stenosis may require revascularization procedures to control hypertension.

Laboratory studies

• BMP
  • Evidence of renal insufficiency (↑ serum creatinine, ↑ BUN, hyperkalemia)
  • Hypokalemia (uncommon) ^[17][18]
• Urinalysis: Proteinuria may be present.
• Tests to identify the underlying cause: See “Etiology.”

• Acute kidney injury
• Chronic glomerulonephritis
• Essential hypertension
• Malignant hypertension
• Renovascular hypertension
• Hypertensive nephrosclerosis
• Uremia

The differential diagnoses listed here are not exhaustive.

Renal infarction refers to the acute loss of blood supply to the renal parenchyma resulting in necrosis and loss of kidney function.

Etiology

Renal infarction is usually caused by thromboemboli or in situ thrombosis with any of the following etiologies:

• Idiopathic cause
• Cardiovascular disease: atrial fibrillation, endocarditis, valvular or ischemic heart disease
• Renal artery disease: renal artery dissection, Marfan syndrome, polyarteritis nodosa, fibromuscular dysplasia
• Hypercoagulable states: antiphospholipid syndrome, polycythemia vera, factor V Leiden

Clinical features

• Fever
• Acute onset flank or abdominal pain
• Nausea and vomiting
• Increased blood pressure
• Oliguria

Diagnostics

Diagnosis is based on the presence of clinical features. Imaging confirms the diagnosis.

• Laboratory studies
  • CBC: leukocytosis
  • Serum: ↑ creatinine and lactate dehydrogenase
  • Urinalysis and culture: frank or microscopic hematuria and proteinuria without casts
• Imaging studies (confirmatory)
  • Abdominal CT scan
    • CT without contrast is the preferred initial study (to rule out urolithiasis).
    • CT angiogram if there are no signs of urolithiasis or pyelonephritis to evaluate for infarction: characteristically shows a wedge-shaped perfusion defect
  • Color Doppler ultrasound: decreased or absent blood flow
• Other: Assess for cardiovascular causes.
  • Electrocardiography
  • Echocardiography

Differential diagnoses

• Urolithiasis
• Pyelonephritis

Treatment

• Antihypertensive therapy (e.g., ACE inhibitors, ARBs)
• Anticoagulation (e.g., direct oral anticoagulants, warfarin)
• Percutaneous endovascular therapy (e.g., thrombolysis, thrombectomy with or without angioplasty)

References: ^[19][20]

Approach ^{[8][14][15][21][22]}

• Medical therapy: preferred initial therapy in all patients
  • Treatment of hypertension, preferably with ACE inhibitors or ARBs, is indicated in all patients. ^[11]
  • Treatment of the underlying cause (e.g., treatment of atherosclerosis)
• Good response to optimal medical therapy : Continue medical therapy indefinitely.
• Poor response to optimal medical therapy: Consider revascularization procedures (endovascular/surgical).
• Hemodynamically significant renal artery stenosis with cardiac disease, complicated HTN, chronic renal insufficiency, or a solitary functional kidney: Revascularization is typically required to control HTN and prevent worsening of renal function.

Medical therapy

All patients with symptomatic or asymptomatic renal artery stenosis should be initiated on medical therapy to control HTN and treat the underlying disease.

Treatment of associated hypertension ^[8][11][23]

• General principles
  • Multiple agents may be required to achieve blood pressure control.
  • Regimens including an ACE inhibitor or an ARB are preferable.
  • Monitor renal function if ACE inhibitors or ARBs are initiated ; discontinue these medications if renal function worsens. ^[24]
  • Avoid hypotension, especially in patients who do not undergo revascularization. ^[24]
  • Antihypertensive therapy may need to be continued indefinitely. ^[23]
• Options
  • ACE inhibitors (e.g., lisinopril )
  • Angiotensin receptor blockers (e.g., losartan )
  • Calcium channel blockers (e.g., amlodipine )
  • Beta blockers (e.g., metoprolol )

Closely monitor serum creatinine and K⁺ after initiating ACE inhibitors or ARBs, especially in patients with bilateral renal artery stenosis. Onset or rapid worsening of renal dysfunction can often be reversed by promptly discontinuing the agent.

Treatment of atherosclerosis ^[15][21]

• Lifestyle modification (see “Treatment of atherosclerosis” for details)
• High-intensity statin therapy (i.e., atorvastatin or rosuvastatin ) unless contraindicated ^[25]
• Glycemic control in patients with diabetes
• Consider antiplatelet therapy.

Revascularization procedures ^[8][13][14]

General principles

• Not routinely recommended for patients with well-controlled HTN on optimal medical therapy ^[26]
• Only of moderate benefit in patients with fibromuscular dysplasia and of uncertain benefit in patients with atherosclerotic renal artery stenosis ^[14][27]
• Unlikely to be beneficial in patients with small, nonviable kidneys ^[14]
• Should be reserved primarily for patients with poor response to optimal medical therapy or those with severe bilateral disease or stenosis affecting a solitary functioning kidney

Indications ^[13][14]

• Hemodynamically significant renal artery stenosis with any of the following:
  • Heart failure with recurrent acute decompensations
  • Sudden unexplained acute pulmonary edema
  • Uncontrolled unstable angina despite maximal medical therapy
  • Complicated or severe hypertension
    • Resistant HTN
    • Intolerance to antihypertensives ^[14]
    • HTN with acute end-organ damage (hypertensive emergency)
    • HTN with an unexplained unilateral small kidney
    • Acute worsening of previously controlled HTN
• Bilateral stenosis or stenosis of a single functioning kidney:
  • With progressive renal insufficiency
  • Or asymptomatic patients with hemodynamically significant renal artery stenosis

Options ^[11][27][28]

• Endovascular revascularization: percutaneous transluminal renal angioplasty
  • Indications: appropriate for most patients who require intervention
  • Procedure
    • Atherosclerotic disease: balloon angioplasty with stenting of the stenotic segment(s)
    • Fibromuscular dysplasia: balloon angioplasty typically without stenting
  • Potential risks: injury at the vascular access site, atheroembolism, retroperitoneal hematoma, and renal artery dissection or rupture
• Surgical revascularization: aortorenal bypass surgery
  • Indications
    • Fibromuscular dysplasia either with macroaneurysms or affecting smaller branches of renal arteries
    • Atherosclerotic disease affecting multiple small renal arteries
    • Concomitant conditions requiring open surgical repair (e.g., abdominal aortic aneurysm)
  • Disadvantages: potential morbidity and mortality risks of open surgical repair

Further management ^[14]

• Dose reduction of antihypertensive agent(s) as required
• Serial postprocedural duplex US to monitor response to therapy and identify restenosis