What is the treatment for Acute Interstitial Nephritis (AIN)?

Treatment for Acute Interstitial Nephritis (AIN)

The primary treatment for acute interstitial nephritis (AIN) includes immediate discontinuation of the causative agent followed by corticosteroid therapy, with prednisone 0.5-1 mg/kg/day orally for Grade 2 or methylprednisolone 1-2 mg/kg/day IV for Grade 3-4 disease. 1

Diagnosis and Initial Assessment

• AIN is a common cause of acute kidney injury (AKI), with drug-induced AIN accounting for 60-70% of cases 2

• Common causative agents include:

  • Antibiotics
  • NSAIDs
  • Proton pump inhibitors (PPIs)
  • Immune checkpoint inhibitors (ICIs)

• Diagnostic findings:

  • Urinalysis may show pyuria, hematuria, white cell casts, and eosinophiluria 1
  • Fractional excretion of urea (FEUrea) <28% has a sensitivity of 75% and specificity of 83% 1
  • Kidney biopsy is the gold standard for definitive diagnosis 2

Treatment Algorithm

Step 1: Identify and Remove Causative Agent

• Immediately discontinue the suspected causative medication 1, 2
• Determine nephrotoxic causality by assessing:
  • Temporal relationship between drug administration and AKI onset
  • Exclusion of other possible causes
  • Response to drug removal 3

Step 2: Supportive Care

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

Step 3: Corticosteroid Therapy

Based on severity grade:

Grade	Treatment Approach
Grade 1	Temporarily hold medications and monitor creatinine weekly [1]
Grade 2	Prednisone 0.5-1 mg/kg/day orally, taper over 4-6 weeks if improved [1]
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 [1]

Step 4: For Refractory Cases

• Consider additional immunosuppression if no improvement after 3-5 days or worsening:

  • Infliximab
  • Azathioprine
  • Cyclophosphamide
  • Cyclosporine
  • Mycophenolate mofetil 1

• Consider renal replacement therapy for:

  • Hyperkalemia
  • Refractory acidosis
  • Volume overload
  • Uremic symptoms 1

Special Considerations

Timing of Corticosteroid Therapy

• Early administration of corticosteroids (within 7 days of diagnosis) improves recovery and decreases risk of chronic renal impairment 1
• Studies show that prolonged treatment beyond 8 weeks does not further improve kidney function recovery 4

Immune Checkpoint Inhibitor-Induced AIN

• For immune-related AIN:
  • Interrupt or permanently discontinue ICI therapy depending on severity 3
  • Start (methyl)prednisone 1 mg/kg or consider pulse methylprednisolone for stage 3 AKI 3
  • Consider renal biopsy on a case-by-case basis 3

Monitoring and Follow-up

• Monitor serum creatinine prior to every dose of checkpoint inhibitor therapy if applicable 1
• For Grade 1-2 nephritis that resolves to Grade 1 or less, ICI therapy may be resumed once steroids have been successfully tapered to ≤10 mg/day or discontinued 1

Prognosis

• Early diagnosis and treatment are crucial for better outcomes 1, 2
• AIN has a higher rate of non-recovery at 6 months compared to acute tubular necrosis 1
• In general, prognosis for drug-induced AIN is good with at least partial recovery of kidney function when treated promptly 5
• Avoid re-exposure to the causative agent due to high risk of recurrence 1

Pitfalls to Avoid

• Delaying corticosteroid therapy beyond 7 days of diagnosis significantly worsens outcomes 1
• Reflex kidney biopsy should be discouraged until steroid treatment has been attempted 1
• Combining nephrotoxins can result in pharmacodynamic drug interactions, such as the "triple whammy" of NSAIDs, diuretics, and ACE inhibitors/ARBs 3