A 60-year-old with chronic kidney disease (eGFR 35 mL/min) takes ibuprofen regularly for knee pain and is found to have acute worsening of renal function. The pathophysiological mechanism by which NSAIDs impair renal function in CKD is:

• A NSAIDs inhibit renin secretion, reducing angiotensin II-mediated efferent arteriolar tone
• B NSAIDs directly toxic to proximal tubular cells by uncoupling oxidative phosphorylation
• C COX-2 inhibition reduces tubuloglomerular feedback sensitivity, causing uncontrolled hyperfiltration
• D Prostaglandin E2 and prostacyclin normally maintain afferent arteriolar vasodilation in compromised renal perfusion; NSAIDs abolish this compensatory response ✓

Explanation

Under conditions of reduced renal perfusion (CKD, heart failure, volume depletion), the kidney relies on locally synthesized PGE2 and prostacyclin (PGI2) to maintain afferent arteriolar vasodilation and GFR. In patients with normal renal perfusion, prostaglandins play a minor hemodynamic role; but in CKD, NSAIDs eliminating this prostaglandin-mediated compensation cause afferent vasoconstriction, sharp reduction in GFR, and acute-on-chronic kidney injury.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.