Can Angiotensin-Converting Enzyme (ACE) inhibitors and steroids be given simultaneously in patients with Acute Kidney Injury (AKI)?

ACE Inhibitors and Steroids in Acute Kidney Injury

ACE inhibitors (and ARBs) should be discontinued immediately when AKI is diagnosed and should not be given simultaneously with any medications during the acute phase of kidney injury, as they block critical compensatory mechanisms that maintain glomerular filtration pressure during renal hypoperfusion. 1

Why ACE Inhibitors Must Be Stopped in AKI

The fundamental problem is hemodynamic: ACE inhibitors block angiotensin II-mediated efferent arteriolar constriction, which is the kidney's primary mechanism for maintaining glomerular filtration pressure when renal perfusion is compromised. 1 During AKI, this protective mechanism becomes critical—blocking it causes the glomerular filtration pressure gradient to collapse, worsening kidney function independent of blood pressure changes. 1

• Multiple guideline societies including the American College of Cardiology explicitly recommend avoiding ACE inhibitors and ARBs during active AKI episodes. 1
• The combination of ACE inhibitors or ARBs with other RAAS blockers substantially increases risks of hyperkalemia, syncope, and AKI without cardiovascular benefit. 2

Clinical Scenarios Where Risk Is Highest

ACE inhibitors pose particular danger during AKI when combined with:

• Volume depletion from diarrhea, vomiting, or sepsis 1, 3
• Concurrent diuretic therapy, especially in older patients 3
• Pre-existing chronic kidney disease 3, 4
• Heart failure with reduced effective circulating volume 3
• Concomitant NSAIDs or other nephrotoxic drugs 2, 3

A study of 27 patients who developed AKI on ACE inhibitors found that 22 had two or more risk factors present, with overt volume depletion in 21 cases and hypotension in 12 cases. 3 Notably, none had renal artery stenosis, demonstrating that ACE inhibitor-induced AKI occurs even without anatomic lesions. 3

Immediate Management Algorithm

When AKI is diagnosed in a patient on ACE inhibitors:

1. Discontinue the ACE inhibitor immediately 1
2. Assess volume status—if volume depleted, restore euvolemia 1
3. Substitute with alternative antihypertensives that have minimal renal hemodynamic effects, such as dihydropyridine calcium channel blockers (e.g., amlodipine) 1, 5
4. Monitor serum creatinine and potassium closely 1

Regarding Steroids

The question asks about steroids, but there is no contraindication to using corticosteroids during AKI—the concern is specifically with ACE inhibitors/ARBs. Steroids can be given during AKI when clinically indicated (e.g., for acute interstitial nephritis, vasculitis, or other inflammatory conditions causing AKI). The critical issue is that ACE inhibitors must be stopped.

When to Consider Reintroduction

ACE inhibitors should only be restarted after ALL of the following criteria are met: 1, 5, 6

• GFR has stabilized (not just improved, but stable over several days)
• Volume status is optimized and euvolemic
• Acute precipitating illness has resolved
• Mean arterial pressure >65 mmHg
• Serum potassium <5.5 mEq/L

Reintroduction protocol: 1, 5

• Start with lower doses than previously used
• Recheck renal function and potassium within 1 week of restarting
• Accept creatinine increases up to 10-20% as expected hemodynamic effects
• Discontinue immediately if creatinine rises >20% or potassium exceeds 5.5 mEq/L

Evidence Supporting Reintroduction After Recovery

Importantly, permanent discontinuation after AKI recovery is harmful. The most recent meta-analysis of 70,801 patients found that continued use of ACE inhibitors/ARBs after AKI recovery was associated with lower all-cause mortality (OR 0.63), lower recurrent AKI risk (OR 0.78), and reduced progression to CKD. 7 A separate ICU cohort study showed 1-year mortality reduction with ACE inhibitor/ARB prescription at ICU discharge in AKI survivors (HR 0.48). 8

Critical Pitfalls to Avoid

• Never combine ACE inhibitors with ARBs or direct renin inhibitors—this substantially increases hyperkalemia and AKI risk without benefit. 2, 1
• Avoid concomitant potassium supplements or potassium-sparing diuretics during or immediately after AKI. 1
• Do not restart prematurely—wait for complete stabilization, as premature reinitiation risks recurrent AKI. 1
• Do not permanently discontinue after AKI recovery, as this increases long-term mortality and cardiovascular events. 7, 8