What are the features of Acute Interstitial Nephritis (AIN)?

Features of Acute Interstitial Nephritis (AIN)

Acute interstitial nephritis is characterized by inflammation of the kidney interstitium with predominant lymphocyte and monocyte infiltration, commonly caused by drugs (70-92% of cases), and presenting with nonspecific symptoms that may include fever, rash, and eosinophilia, though this classic triad is present in less than one-third of cases.

Clinical Presentation

Symptoms and Signs

• Nonspecific symptoms including:
  • Malaise, nausea, and vomiting
  • Oliguria (in 51% of cases) 1
  • Fever (in 30% of cases) 1
  • Skin rash (in 21% of cases) 1
  • Arthralgia (in 45% of cases) 1
  • Loin pain (in 21% of cases) 1

Laboratory Findings

• Acute kidney injury (elevated serum creatinine)
• Urinalysis showing:
  • Pyuria
  • Hematuria
  • White cell casts
  • Eosinophiluria (though not consistently present)
  • Tubular non-nephrotic range proteinuria 2
• Fractional excretion of urea (FEUrea) <28% (sensitivity 75%, specificity 83%) 3

Etiology

Drug-Induced AIN (70-92% of cases)

• Most common causative agents:
  • Antibiotics (49% of drug-induced cases) 1
  • Proton pump inhibitors (14% of drug-induced cases) 1
  • NSAIDs (11% of drug-induced cases) 1
  • Top specific drugs: omeprazole (12%), amoxicillin (8%), ciprofloxacin (8%) 1

Other Causes

• Autoimmune diseases (20% of cases) 1
• Infections (4-10% of cases) 1, 4
• Idiopathic (4-8% of cases) 2, 4
• Immune checkpoint inhibitor therapy (presenting as AIN in 80-90% of immune-related renal dysfunction) 5

Pathophysiology

• Idiosyncratic delayed type IV hypersensitivity reaction (in drug-induced cases) 2
• Immune-mediated tubulointerstitial injury 6

Diagnostic Features

Histopathology (Gold Standard)

• Extensive interstitial infiltrate primarily composed of:
  • Lymphocytes and monocytes
  • Variable presence of eosinophils, plasma cells, histiocytes, and polymorphonuclear cells 2
• Interstitial edema
• Tubular injury with varying degrees of tubular atrophy
• Interstitial granulomas (in 31% of cases with prolonged drug exposure) 4
• Minimal glomerular involvement

Imaging

• Renal ultrasound typically normal or shows enlarged kidneys
• May show evidence of renal shrinkage in more chronic cases 4

Prognostic Factors

Poor Prognostic Indicators

• Longer duration of drug exposure (15 days for complete recovery vs 130 days for no recovery) 1
• Delayed withdrawal of the causative agent 2
• Delayed initiation of steroid therapy (8 days for complete recovery vs 35 days for no recovery) 1
• Histological features of chronicity:
  • Tubular atrophy
  • Interstitial granulomas
  • Pronounced interstitial cell infiltration 4
• NSAIDs as the causative agent (56% risk of permanent renal insufficiency) 4
• Chronic use of mixed analgesics and/or NSAIDs 4

Management Considerations

Immediate Actions

• Withdrawal of the suspected causative agent 2
• Supportive care for acute kidney injury
• Consideration of corticosteroid therapy, especially if no improvement within 5-7 days after drug withdrawal 2

Monitoring

• Regular assessment of renal function
• Close monitoring for recovery (complete recovery defined as improvement in serum creatinine to within 25% of baseline) 1

Outcomes

• Complete recovery: 49% of drug-induced AIN cases treated with steroids 1
• Partial recovery: 39% of drug-induced AIN cases treated with steroids 1
• No recovery: 12% of drug-induced AIN cases treated with steroids 1
• Higher risk of non-recovery compared to acute tubular necrosis (2.71-fold higher risk) 3

Understanding these features of AIN is crucial for early diagnosis and appropriate management to prevent progression to chronic kidney disease and improve patient outcomes.