Diagnosis	Key Differentiator
AKI	Sudden ↑Cr, prerenal labs (FEurea <35%).
AIN	Fever/rash/eosinophilia, WBC casts, steroid response.
Chronic Interstitial	Slow CKD progression, small kidneys on imaging.
Papillary Necrosis	Gross hematuria, Flank pain, Sloughed papillae in urine, CT “ring sign”.
Nephrotic Syndrome	Massive proteinuria, hypoalbuminemia, edema.

1. Acute Kidney Injury (AKI)

• Mechanism: NSAIDs inhibit COX-1/COX-2, reducing vasodilatory prostaglandins (PGE₂, PGI₂), leading to afferent arteriolar vasoconstriction and decreased glomerular filtration rate (GFR).
• Types:
  • Prerenal AKI: Reversible with hydration and NSAID discontinuation.
  • Intrinsic AKI (e.g., acute tubular necrosis): Prolonged ischemia from severe vasoconstriction.

2. Acute Interstitial Nephritis (AIN)

• Mechanism: Immune-mediated hypersensitivity reaction, often with eosinophilic infiltration.
• Features: May present with fever, rash, eosinophilia, and AKI. Requires steroid therapy in severe cases.

3. Chronic Interstitial Nephritis

• Mechanism: Long-term NSAID use causes chronic inflammation and fibrosis.
• Outcome: Progressive chronic kidney disease (CKD) with tubular atrophy and interstitial scarring.

4. Renal Papillary Necrosis

• Mechanism: Chronic ischemia due to reduced medullary blood flow, exacerbated by long-term NSAID use.
• Features: Hematuria, flank pain, and sloughed papillae causing urinary obstruction.

5. Nephrotic Syndrome

• Types:
  • Minimal Change Disease: Podocyte injury from NSAID-induced cytokine release.
  • Membranous Nephropathy: Rare, immune-complex deposition.
• Presentation: Proteinuria (>3.5 g/day), hypoalbuminemia, edema.