Is the acute renal deterioration in this elderly man with hypertension, type‑2 diabetes, chronic ACE‑inhibitor (enalapril) use and recent etoricoxib (COX‑2 inhibitor) therapy simply a flare of chronic kidney disease rather than drug‑induced acute kidney injury?

This is Drug-Induced Acute Kidney Injury, Not Simply a CKD Flare

The acute renal deterioration in this elderly diabetic man on chronic enalapril who recently started etoricoxib represents drug-induced acute kidney injury (AKI), specifically from the synergistic nephrotoxic effect of combining an ACE inhibitor with a COX-2 inhibitor in a high-risk patient. 1, 2

Why This is AKI Rather Than CKD Progression

The Triple-Hit Mechanism

This patient experienced a "triple-hit" nephrotoxic insult:

• Chronic ACE inhibitor (enalapril) reduces efferent arteriolar tone, making GFR dependent on afferent arteriolar vasodilation 3
• COX-2 inhibitor (etoricoxib) blocks prostaglandin-mediated afferent arteriolar dilation 2
• High-risk substrate: elderly age, diabetes, hypertension, and pre-existing CKD create critical dependence on these compensatory mechanisms 1

When NSAIDs/COX-2 inhibitors are combined with ACE inhibitors in elderly or volume-depleted patients, dual inhibition of both afferent (prostaglandin) and efferent (angiotensin II) arteriolar regulation causes acute renal failure 2. This is a well-recognized drug-drug interaction that produces reversible AKI, not CKD progression 4.

Evidence Supporting Drug-Induced AKI

• Each additional nephrotoxic medication raises AKI odds by 53%, and multiple nephrotoxins more than double the risk 5
• In elderly patients with CKD on ACE inhibitors, 45% experience overdosing, which accounts for most excess AKI risk 6
• ACE inhibitor-associated acute renal failure is almost always reversible within 2-3 days after drug cessation 3, distinguishing it from irreversible CKD progression
• The FDA label explicitly warns that co-administration of NSAIDs (including COX-2 inhibitors) with ACE inhibitors in elderly or volume-depleted patients results in deterioration of renal function, including possible acute renal failure, and these effects are usually reversible 2

Clinical Decision Algorithm

Step 1: Immediate Actions

• Discontinue etoricoxib immediately – the COX-2 inhibitor is non-essential and a suitable alternative (acetaminophen) exists 1
• Temporarily hold enalapril during the acute phase 1, 3, 7
• Assess and restore volume status – dehydration dramatically amplifies risk (OR 30.8) 6

Step 2: Distinguish AKI from CKD Progression

Features favoring drug-induced AKI in this case:

• Temporal relationship: renal deterioration followed recent etoricoxib initiation 1
• High-risk drug combination: ACE inhibitor + NSAID in elderly diabetic 2, 6
• Reversibility expected: ACE inhibitor-induced renal dysfunction reverses within 2-3 days of cessation 3, 4

If this were simple CKD progression, you would NOT expect:

• Acute onset coinciding with new medication
• The specific ACE inhibitor + NSAID combination
• Rapid reversibility after drug withdrawal

Step 3: Monitoring During Recovery

• Check serum creatinine every 48 hours until stabilization 1
• Monitor serum potassium – ACE inhibitors cause hyperkalemia, especially in diabetics 1
• Expect improvement within 2-3 days if drug-induced 3

Step 4: Restarting Enalapril After Recovery

Wait for GFR stabilization and volume optimization before reintroducing enalapril 3:

• Start with lower dose
• Recheck creatinine and potassium within 1 week of restart 1, 3
• Accept creatinine rises up to 30% from baseline – these are expected hemodynamic effects that predict long-term renal protection, not injury 3
• Discontinue if creatinine rises >30% within first 2 months or if hyperkalemia (K ≥5.6 mmol/L) develops 3

Critical Pitfalls to Avoid

Pitfall 1: Misattributing AKI to CKD Progression

The combination of ACE inhibitor + NSAID in an elderly diabetic is a classic setup for reversible drug-induced AKI 2, 6. Failing to recognize this leads to:

• Unnecessary permanent discontinuation of renoprotective ACE inhibitor
• Missed opportunity for rapid recovery by stopping the offending agent

Pitfall 2: Permanently Stopping the ACE Inhibitor

• ACE inhibitors provide long-term renoprotection in diabetic nephropathy 1
• Temporary withdrawal during acute illness is appropriate, but permanent cessation increases 30-day mortality 1
• The culprit here is the etoricoxib, not the enalapril 2

Pitfall 3: Failing to Counsel on "Sick Day" Rules

Patients on ACE inhibitors must hold the medication during intercurrent illness (vomiting, diarrhea, reduced oral intake) to prevent volume-depletion-related AKI 3, 7. This patient should have been counseled to stop enalapril if starting an NSAID or becoming volume-depleted.

Pitfall 4: Restarting Too Aggressively

• Do not restart enalapril until volume status is optimized and GFR has stabilized 1, 3
• When restarting, monitor creatinine within 1 week 1
• Avoid combining with other nephrotoxins (NSAIDs, contrast, aminoglycosides) 1, 5

Summary of Evidence Quality

The strongest evidence comes from:

• ADQI 2017 consensus guidelines on nephrotoxin management in AKI 1
• FDA enalapril label explicitly warning about NSAID combination 2
• ACC/AHA guidance on ACE inhibitor-induced creatinine changes 3
• Prospective study showing 45% ACE inhibitor overdosing in elderly CKD patients causes excess AKI 6

This clinical scenario represents a textbook case of preventable, reversible drug-induced AKI from a recognized drug-drug interaction, not CKD progression. 1, 2, 6