A 68-year-old man with decompensated heart failure (ejection fraction 25%) and mild baseline renal impairment (creatinine 1.8 mg/dL) presents to the emergency department. His wife reports he has been taking ibuprofen 400 mg three times daily for chronic knee pain for the past 2 weeks. On examination, he is orthostatic and clinically volume-depleted. His serum creatinine has risen to 3.2 mg/dL, and urinalysis shows no proteinuria or casts. The structure marked **A** in the diagram is the site of action of a critical autoregulatory mechanism that has been disrupted in this patient. Which of the following best explains the acute kidney injury in this clinical scenario?

Explanation

## Why option 1 is correct The afferent arteriole (**A**) is normally dilated by prostaglandins (PGE2 and PGI2), which maintain glomerular filtration pressure and GFR during states of decreased renal perfusion (hypovolemia, CHF, cirrhosis). NSAIDs block cyclooxygenase and inhibit prostaglandin synthesis, removing this vasodilatory signal. In a volume-depleted patient with CHF, the kidneys are already dependent on prostaglandin-mediated afferent vasodilation to maintain GFR. NSAID-induced constriction of the afferent arteriole drops glomerular capillary hydrostatic pressure below the filtration threshold, causing acute kidney injury. This is the classic mechanism of NSAID-induced AKI in susceptible populations (Guyton & Hall 14e Ch 27; KD Tripathi 9e Ch 41). ## Why each distractor is wrong - **Option 2**: NSAIDs do not block angiotensin II receptors—that is the mechanism of ARBs. Angiotensin II constricts the *efferent* arteriole, not the afferent. NSAIDs have no direct effect on angiotensin II signaling. - **Option 3**: NSAIDs do not inhibit renin release; in fact, by reducing renal perfusion pressure, NSAIDs may *increase* renin secretion. Efferent arteriolar constriction (from unopposed angiotensin II) would actually *increase* glomerular pressure, not cause collapse. - **Option 4**: NSAIDs do not increase sympathetic tone. Sympathetic activation would constrict the afferent arteriole directly, but this is not the primary mechanism of NSAID nephrotoxicity. The key mechanism is loss of prostaglandin-mediated vasodilation. **High-Yield:** In volume-depleted states (hypovolemia, CHF, cirrhosis, elderly), the kidney becomes prostaglandin-dependent for afferent vasodilation and GFR maintenance—NSAIDs are contraindicated because they block this critical protective mechanism. [cite:Guyton & Hall 14e Ch 27; KD Tripathi 9e Ch 41]