A 52-year-old man with hypertension on enalapril and type 2 diabetes on metformin presents with acute kidney injury. His serum creatinine has risen from 1.2 to 3.8 mg/dL over 48 hours following initiation of an NSAID for joint pain. Which is the most common mechanism of drug interaction responsible for this acute deterioration in renal function?

Explanation

## Mechanism of NSAID-ACE Inhibitor-Induced Acute Kidney Injury **Key Point:** The most common mechanism is inhibition of renal prostaglandin synthesis by NSAIDs, which reduces glomerular filtration pressure, especially in the setting of ACE inhibition. ### Pathophysiology NSAIDs inhibit cyclooxygenase (COX), blocking prostaglandin E~2~ (PGE~2~) and prostacyclin synthesis in the kidney. These prostaglandins normally maintain renal blood flow and glomerular filtration pressure by causing afferent arteriolar vasodilation. **High-Yield:** When ACE inhibitors are also present, the kidney loses two protective mechanisms: 1. Loss of prostaglandin-mediated afferent vasodilation (from NSAID) 2. Loss of angiotensin II–mediated efferent vasoconstriction (from ACE inhibitor) This dual blockade results in severe reduction in glomerular filtration pressure and acute kidney injury, particularly in patients with pre-existing renal disease or volume depletion. ### Clinical Pearl This "triple whammy" interaction (NSAID + ACE inhibitor + volume depletion or diabetes) is a well-recognized cause of acute kidney injury in primary care and is frequently tested in NEET PG. The onset is typically within 48–72 hours of NSAID initiation. ### Why This Matters | Feature | Detail | | --- | --- | | **Most common site of action** | Afferent arteriole of glomerulus | | **Reversibility** | Usually reversible if NSAID stopped promptly | | **Risk factors** | Pre-existing renal disease, diabetes, volume depletion, age >65 | | **Prevention** | Avoid NSAIDs in patients on ACE-I/ARB; use alternatives (acetaminophen, topical NSAIDs) | [cite:KD Tripathi 8e Ch 14]