What is the management of acute interstitial nephritis?

Management of Acute Interstitial Nephritis (AIN)

The management of acute interstitial nephritis requires prompt identification and removal of the offending agent, followed by corticosteroid therapy within 7 days of diagnosis to improve recovery and decrease the risk of chronic renal impairment. 1

Etiology and Diagnosis

• Common causes:

  • Drugs (70% of cases) 2
    • Antibiotics (49% of drug-induced cases)
    • Proton pump inhibitors (14%)
    • NSAIDs (11%)
  • Autoimmune diseases (20%)
  • Infections (4%)
  • Immunotherapy-related (presents as AIN in 80-90% of cases) 1

• Diagnostic findings:

  • Urinalysis: pyuria, hematuria, white cell casts, eosinophiluria
  • Fractional excretion of urea <28% (sensitivity 75%, specificity 83%) 1
  • Kidney biopsy: definitive diagnosis showing interstitial inflammation, tubular damage, and sometimes granulomas 3

Treatment Algorithm

1. Immediate Management

• Identify and discontinue the offending agent immediately 3
  • Early discontinuation is critical for recovery
  • Prolonged exposure (>1 month) associated with 88% risk of permanent renal insufficiency 4

2. Corticosteroid Therapy

• Initiate corticosteroids early (within 7 days of diagnosis) 1

• Dosing regimen based on severity:

  Grade	Treatment
  Grade 1	Temporarily hold medications and monitor creatinine weekly
  Grade 2	Prednisone 0.5-1 mg/kg/day orally, taper over 4-6 weeks if improved
  Grade 3-4	Methylprednisolone 1-2 mg/kg/day IV, consider pulse methylprednisolone in severe cases, taper over at least 4 weeks once improved to Grade 1

• Duration: Treatment beyond 8 weeks does not further improve kidney function recovery 3

3. Supportive Care

• Maintain euvolemia
• Avoid nephrotoxic exposures
• Adjust medication dosages based on renal function 1
• Monitor serum creatinine regularly

4. Special Considerations for Immunotherapy-Related AIN

• Permanently discontinue immune checkpoint inhibitor therapy
• Consult nephrology urgently
• Consider additional immunosuppression (infliximab, azathioprine, cyclophosphamide, cyclosporine, or mycophenolate mofetil) if no improvement after 3-5 days 1

Prognostic Factors

• Poor prognostic factors:

  • Longer duration of drug exposure (15 vs 30 vs 130 days for complete, partial, and no recovery) 5
  • Longer delay in starting steroid therapy (8 vs 11 vs 35 days) 5
  • Presence of tubular atrophy on histology 4
  • Interstitial granulomas 4
  • Pronounced interstitial cell infiltration 4

• Outcomes:

  • Complete recovery: 49% of drug-induced AIN treated with steroids
  • Partial recovery: 39%
  • No recovery: 12% 5
  • NSAID-induced AIN has worst prognosis (56% permanent renal insufficiency) 4

Monitoring and Follow-up

• Weekly creatinine monitoring until improvement
• Avoid re-exposure to the causative agent due to high risk of recurrence 1
• Consider renal replacement therapy for severe cases with hyperkalemia, refractory acidosis, volume overload, or uremic symptoms 1

Caveats and Pitfalls

• AIN is often underdiagnosed as a cause of acute kidney injury 2
• Classic triad of fever, rash, and arthralgias may be absent in up to two-thirds of patients 6
• Subacute symptoms and prolonged drug intake suggest a more chronic course 4
• Infection-induced and idiopathic AIN typically have better outcomes than drug-induced cases 4
• Kidney biopsy may not be necessary if rapid improvement occurs after removal of the offending agent 6