What are the considerations for using Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) in a patient with unilateral renal artery stenosis?

ACE Inhibitors and ARBs in Unilateral Renal Artery Stenosis

ACE inhibitors and ARBs are recommended as first-line antihypertensive therapy in patients with unilateral renal artery stenosis, provided close monitoring of renal function is performed. 1

Primary Recommendation for Unilateral RAS

• In patients with unilateral renal artery stenosis and two functioning kidneys, ACE inhibitors or ARBs should be included in the antihypertensive regimen. 1
• The 2024 ESC Guidelines explicitly state that ACEIs/ARBs are Class I, Level B recommendations for treating hypertension associated with unilateral RAS. 1
• The 2017 ESC Guidelines similarly recommend ACEIs/ARBs as first-line therapy for unilateral stenosis. 1

Physiologic Rationale

• In unilateral RAS, the affected kidney releases renin, causing vasoconstriction-mediated hypertension, while the contralateral normal kidney maintains overall renal function. 1
• The unaffected kidney can compensate for any hemodynamic changes induced by ACE inhibitors or ARBs, preventing clinically significant renal dysfunction. 1
• ACE inhibitors work by blocking angiotensin II formation, which reduces efferent arteriolar vasoconstriction and lowers intraglomerular pressure in the stenotic kidney. 1

Monitoring Requirements

• Serum creatinine and potassium must be checked within 2-4 weeks after initiating or increasing the dose of ACE inhibitors or ARBs. 2
• An initial rise in creatinine of 10-20% is expected and acceptable, representing hemodynamic adaptation rather than kidney injury. 2
• If creatinine rises more than 30% from baseline, the medication should be discontinued. 2, 3
• Clinically significant azotemia is defined as greater than 50% rise in serum creatinine that persists after correcting hypoperfusion states such as volume depletion or heart failure. 1

Critical Contraindications

Bilateral renal artery stenosis or stenosis to a solitary kidney represents an absolute contraindication to ACE inhibitors and ARBs. 1, 2, 4

• In bilateral disease or single-kidney stenosis, both kidneys depend on angiotensin II-mediated efferent arteriolar vasoconstriction to maintain glomerular filtration pressure. 1
• Blocking this compensatory mechanism causes acute renal failure by decreasing transglomerular hydrostatic pressure and shunting blood from afferent to efferent arterioles without adequate filtration. 1
• Multiple case reports document reversible acute renal failure when ARBs (losartan, candesartan) were used in bilateral RAS. 5, 6, 7
• The FDA drug label for ACE inhibitors explicitly warns that increases in blood urea nitrogen and serum creatinine may occur in patients with bilateral renal artery stenosis. 3

Nuanced Consideration for Bilateral Disease

• The 2024 ESC Guidelines suggest that ACEIs/ARBs may be considered (Class IIb, Level B) in bilateral RAS if close patient monitoring of renal function is feasible. 1
• This represents a more permissive stance than older guidelines, but requires exceptional vigilance and should only be attempted when the benefits clearly outweigh risks. 1
• The 2017 ESC Guidelines similarly state that ACEIs/ARBs may be considered in bilateral severe RAS if well-tolerated and under close monitoring. 1

High-Risk Clinical Scenarios

ACE inhibitors and ARBs should be temporarily held or avoided in the following situations, even with unilateral stenosis: 2, 3

• Severe volume depletion or aggressive diuresis, as renal perfusion becomes angiotensin-dependent. 2
• Decompensated congestive heart failure in a sodium-depleted state. 1
• Concurrent use of nonsteroidal anti-inflammatory drugs, which further compromise renal perfusion. 1
• Longstanding unilateral RAS with contralateral renal dysfunction (hypertensive nephrosclerosis), which mimics bilateral disease physiology. 1

Alternative Antihypertensive Options

When ACE inhibitors or ARBs cannot be used safely, the following alternatives are recommended: 1

• Calcium channel blockers (first-line alternative). 1
• Beta-blockers (particularly in patients with heart failure or coronary disease). 1
• Diuretics (though caution is needed to avoid volume depletion). 1
• Combination therapy with these agents is often necessary to achieve blood pressure targets in RAS-related hypertension. 1

Common Pitfalls to Avoid

• Do not assume that ARBs are safer than ACE inhibitors in bilateral RAS—both classes cause the same mechanism of renal dysfunction. 5, 6, 7
• Research evidence demonstrates that losartan causes renal dysfunction at the same 10.5% incidence as captopril in elderly heart failure patients. 6
• Never combine ACE inhibitors with ARBs or direct renin inhibitors, as this increases risks of hyperkalemia, hypotension, and acute renal failure without additional benefit. 2
• Always assess for bilateral disease before initiating therapy, as unrecognized bilateral stenosis is a major cause of ACE inhibitor-induced acute renal failure. 1, 4
• The diagnostic clue to RAS is severe hypotension or azotemia provoked by ACE inhibitor or ARB use. 1

Practical Algorithm for Clinical Decision-Making

1. Confirm laterality of stenosis using duplex ultrasound, CTA, or MRA before prescribing ACE inhibitors or ARBs. 1
2. If unilateral stenosis with two kidneys: Initiate ACE inhibitor or ARB as first-line therapy. 1
3. Check baseline creatinine and potassium, then recheck in 2-4 weeks. 2
4. If creatinine rises <30%: Continue therapy with ongoing monitoring. 2
5. If creatinine rises >30%: Discontinue medication and consider alternative antihypertensives. 2, 3
6. If bilateral stenosis or solitary kidney: Avoid ACE inhibitors and ARBs entirely, or use only with exceptional justification and intensive monitoring. 1, 4