A 62-year-old woman with rheumatoid arthritis develops acute kidney injury after 3 months of NSAID therapy. Serum creatinine rises from 0.8 to 2.4 mg/dL. Which is the most common mechanism of NSAID-induced renal injury in this clinical scenario?

## NSAID-Induced Renal Injury Mechanisms **Key Point:** Hemodynamic reduction in glomerular filtration rate (GFR) due to afferent arteriolar vasoconstriction is the most common mechanism of acute NSAID-induced renal injury, accounting for >80% of cases. ### Pathophysiology of Hemodynamic Injury NSAIDs inhibit prostaglandin synthesis, which normally: 1. Maintains afferent arteriolar vasodilation 2. Sustains renal perfusion pressure and GFR 3. Counterbalances the vasoconstrictor effects of angiotensin II and norepinephrine When NSAIDs block COX-1/COX-2: - **Afferent arteriolar vasoconstriction** occurs - **Glomerular capillary pressure** falls - **GFR declines** → acute kidney injury This is **functional** (reversible) if NSAIDs are withdrawn early. ### Mechanisms of NSAID-Induced Renal Injury | Mechanism | Frequency | Onset | Reversibility | Clinical Features | |-----------|-----------|-------|----------------|------------------| | **Hemodynamic (afferent vasoconstriction)** | **>80%** | **Days–weeks** | **Reversible** | **Oliguria, ↑Cr, ↑BUN** | | Acute interstitial nephritis | 10–15% | Weeks–months | Reversible (if caught early) | Rash, fever, eosinophilia | | Papillary necrosis | 5–10% | Months–years | Irreversible | Chronic analgesic nephropathy | | Membranous GN | Rare | Months–years | Variable | Nephrotic syndrome | **Clinical Pearl:** Hemodynamic NSAID nephrotoxicity is most common in elderly patients, those with pre-existing renal disease, volume depletion, or concurrent ACE inhibitor/ARB use (the "triple whammy"). **High-Yield:** The key distinguishing feature is that hemodynamic injury is **functional and reversible** — GFR recovers within days to weeks after NSAID withdrawal, whereas interstitial nephritis or papillary necrosis may cause permanent damage. ### Risk Factors for NSAID-Induced Renal Injury - Age > 65 years - Chronic kidney disease (baseline eGFR < 60) - Volume depletion / dehydration - Congestive heart failure - Concurrent ACE-I/ARB use ("triple whammy" with diuretics) - Diabetes mellitus - Sepsis or critical illness **Mnemonic:** **NSAID Renal Toxicity = HemoDynamic (most common) > Interstitial > Papillary** **Tip:** In a patient with acute rise in creatinine on NSAIDs, always check urine for eosinophils and casts to differentiate hemodynamic injury (bland urine) from interstitial nephritis (eosinophiluria, pyuria).