Should amlodipine be discontinued in a patient who develops acute kidney injury?

Should You Hold Amlodipine in AKI?

No, you should not hold amlodipine in a patient with acute kidney injury—amlodipine is not a nephrotoxin and does not require discontinuation during AKI. 1

Why Amlodipine is Safe in AKI

Amlodipine is fundamentally different from ACE inhibitors and ARBs. While guidelines mandate holding ACE inhibitors and ARBs during AKI because they reduce glomerular filtration pressure through efferent arteriolar vasodilation 2, 3, amlodipine—a dihydropyridine calcium channel blocker—does not affect renal hemodynamics in this manner.

Key Pharmacologic Distinctions

• Amlodipine increases renal blood flow without compromising filtration. In hypertensive patients with normal renal function, therapeutic doses of amlodipine decrease renal vascular resistance and actually increase glomerular filtration rate and effective renal plasma flow without changing filtration fraction or causing proteinuria. 1

• Renal impairment does not alter amlodipine pharmacokinetics. The elimination half-life remains approximately 50 hours regardless of renal function, and dosage adjustment is not necessary even in dialysis-dependent patients. 4, 5

• Amlodipine is hepatically metabolized, not renally cleared. Approximately 90% is converted to inactive metabolites via hepatic metabolism, with only 10% of parent compound excreted in urine. 1

Guideline Framework for Nephrotoxin Management

The ADQI consensus guidelines provide clear criteria for when to discontinue medications in AKI 2:

Discontinue a drug when:

• Causal relationship indicates the drug is the potential cause of AKI
• A suitable and less nephrotoxic alternative is available
• The drug is considered non-essential

Amlodipine meets none of these criteria. It is not listed among nephrotoxins that cause or exacerbate AKI, unlike NSAIDs, aminoglycosides, ACE inhibitors, and ARBs. 2, 6

What You Should Hold in AKI

The evidence clearly identifies the actual culprits:

• ACE inhibitors and ARBs must be temporarily held when GFR is unstable or volume status is not optimized, then reintroduced only after stabilization. 3, 7, 6

• NSAIDs should be stopped immediately and remain discontinued throughout both the persistent and recovery phases of AKI. 6

• Aminoglycosides should be avoided unless they provide a clear efficacy advantage with no suitable alternative. 6

Amlodipine as a Preferred Alternative

Amlodipine is explicitly recommended as a safe alternative antihypertensive during AKI. Guidelines specifically suggest dihydropyridine calcium channel blockers like amlodipine (2.5-10 mg daily) as alternatives to ACE inhibitors/ARBs during acute kidney injury because they have minimal effects on renal hemodynamics. 3

Common Pitfall to Avoid

Do not reflexively hold all antihypertensives when AKI develops. The critical distinction is between drugs that compromise renal autoregulation (ACE inhibitors, ARBs, NSAIDs) and those that do not (calcium channel blockers like amlodipine). Inappropriately discontinuing amlodipine may lead to uncontrolled hypertension and hypertensive rebound, which can worsen outcomes. 2

Practical Management Algorithm

1. Continue amlodipine at current dose during AKI episode 1
2. Immediately discontinue ACE inhibitors, ARBs, and NSAIDs 2, 3, 6
3. Optimize volume status with appropriate fluid resuscitation or diuresis 6
4. Monitor blood pressure and adjust amlodipine dose only if hypotension develops (not due to AKI itself) 1
5. After AKI resolution, consider reintroducing ACE inhibitors/ARBs when GFR stabilizes and volume status is optimized 3

Supporting Evidence from Research

Emerging research even suggests amlodipine may be protective in AKI. Animal studies demonstrate that amlodipine alleviates renal ischemia/reperfusion injury through antioxidant and anti-inflammatory mechanisms, reducing tissue damage and improving kidney function markers. 8 While this requires validation in human trials, it reinforces that amlodipine poses no nephrotoxic risk.

Human pharmacokinetic studies in patients with severe renal impairment, including dialysis-dependent patients, confirm that amlodipine elimination and steady-state concentrations are unaffected by renal dysfunction. 4, 5