What antihypertensive drugs are contraindicated in patients with renal artery stenosis, particularly those with bilateral disease or stenosis in a solitary functioning kidney?

Contraindicated Antihypertensive Drugs in Renal Artery Stenosis

ACE inhibitors, angiotensin receptor blockers (ARBs), and direct renin inhibitors are absolutely contraindicated in patients with bilateral renal artery stenosis or unilateral stenosis in a solitary functioning kidney due to the high risk of acute renal failure. 1, 2

Mechanism of Contraindication

The renin-angiotensin system (RAS) blockers cause acute kidney injury through a specific hemodynamic mechanism in renal artery stenosis:

• ACE inhibitors and ARBs reduce efferent arteriolar tone in the glomerulus, which is critical for maintaining glomerular filtration pressure when afferent blood flow is already compromised by the stenosis 2
• In bilateral stenosis or unilateral stenosis with a solitary kidney, both kidneys depend on angiotensin II-mediated efferent arteriolar constriction to maintain adequate filtration pressure 1
• Blocking this compensatory mechanism precipitates acute renal failure, which can progress to renal artery thrombosis in severe cases 3

Specific Contraindicated Drug Classes

ACE Inhibitors (Absolute Contraindication)

• Examples: Enalapril, lisinopril, ramipril, captopril 2, 4
• The 2024 ESC Guidelines explicitly state these can cause acute renal failure in tight bilateral stenoses or stenosed solitary functioning kidney 1
• Case reports document reversible acute renal failure and even renal artery thrombosis following ACE inhibitor use 5, 3

Angiotensin Receptor Blockers (Absolute Contraindication)

• Examples: Candesartan, losartan, valsartan 2, 6
• ARBs carry the same risk as ACE inhibitors through identical effects on the renin-angiotensin-aldosterone system 2, 5
• A documented case of candesartan-induced reversible renal failure in bilateral renal artery stenosis confirms this contraindication 5

Direct Renin Inhibitors (Absolute Contraindication)

• Example: Aliskiren 2
• The American College of Cardiology warns these may precipitate acute kidney injury in severe bilateral renal artery stenosis 2

Safe Alternative Antihypertensive Agents

First-Line Agents

• Calcium channel blockers are the preferred first-line treatment, particularly dihydropyridines like amlodipine 2.5-10 mg daily or nicardipine 2, 6
• These effectively control blood pressure without compromising renal perfusion or glomerular filtration rate 2, 4

Second-Line Agents

• Beta-blockers (metoprolol 50-200 mg daily) can be added if blood pressure control is inadequate with calcium channel blocker monotherapy 2
• Diuretics are also considered safe first-line alternatives 4

Special Circumstance: Hydralazine

• Hydralazine is NOT contraindicated in renal artery stenosis and can be safely used, particularly in combination with isosorbide dinitrate 1, 7, 8
• However, the 2017 ACC/AHA Guidelines note it is contraindicated specifically in bilateral renal artery stenosis when used for hypertensive emergencies 1
• This emergency contraindication likely relates to unpredictability of response rather than direct renal toxicity 1

Critical Clinical Caveats

Do Not Use RAS Blockers Even With Compelling Indications

• Even if the patient has heart failure or diabetes that would typically warrant ACE inhibitor or ARB therapy, these remain absolutely contraindicated in bilateral renal artery stenosis 2, 6
• The only exception is after successful revascularization with renal artery stenting, when ACE inhibitors may be cautiously reintroduced with extremely close monitoring 8

Unilateral Stenosis With Two Functioning Kidneys

• In unilateral renal artery stenosis with a contralateral normal kidney, ACE inhibitors are probably second-line agents and can be used with careful monitoring, as the contralateral kidney maintains overall renal function 4
• However, rising creatinine on ACE inhibitor therapy should prompt immediate investigation for bilateral disease 4

Monitoring Requirements

• When any antihypertensive is initiated in suspected renal artery stenosis, monitor renal function closely, particularly within the first 2-3 days and then monthly for 3 months 6, 7
• Increasing plasma creatinine on ACE inhibitor or ARB therapy is a red flag for undiagnosed bilateral renal artery stenosis 4

Revascularization Considerations

• The 2024 ESC Guidelines recommend percutaneous transluminal renal angioplasty (PTRA) without stenting for fibromuscular dysplasia and PTRA with stenting for atherosclerotic disease 1
• After successful revascularization, RAS blockers may become safe options, though this requires specialist guidance 8