Definition

Acute tubulointerstitial nephritis (ATIN) is an acute inflammation of the renal interstitium and tubules that causes a decline in renal function over a period of days to weeks.

Etiology

Medications (most common)

• Antibiotics: β-lactams, sulfonamides, rifampin, fluoroquinolones
• NSAIDs
• Proton pump inhibitors and H2 blockers
• Loop diuretics and thiazides
• Anticonvulsants: phenytoin, valproate, carbamazepine, phenobarbital
• Other: allopurinol

Pathophysiology

• Immune-mediated tubulointerstitial damage (allergic interstitial nephritis) is the most widely accepted theory.
  • Inflammatory infiltrates → tissue edema and tubular cell damage → compromised tubular flow
  • Allergic interstitial nephritis: drugs act as haptens → type IV hypersensitivity reaction
• Acute obstruction: crystals (from e.g., uric acid, medications) or proteins (e.g., light chains) obstruct tubules

Clinical features

Clinical features of acute kidney injury, with or without:

• Morbilliform rash
  • Caused by Type IV hypersensitivity reaction
• Fever
• Arthralgias
• New drug exposure

Diagnostics

• Blood tests
  • BMP: ↑ BUN and creatinine
  • CBC: ↑ eosinophils (more common in drug-induced ATIN)
• Urine studies
  • Urinalysis
    • Sterile pyuria
    • Subnephrotic-range proteinuria
  • Microscopic hematuria
    • Urine microscopy
    • WBC casts , RBC casts , waxy casts , granular casts , tubular epithelial casts
    • Urine eosinophils (low sensitivity and specificity for ATIN)

Treatment