What is the treatment for interstitial nephritis?

Treatment of Interstitial Nephritis

The first-line treatment for interstitial nephritis is corticosteroid therapy, with prednisone 0.5-1 mg/kg/day for mild-moderate cases and methylprednisolone 1-2 mg/kg/day IV for severe cases, along with immediate discontinuation of the offending agent. 1, 2

Diagnostic Approach

Before initiating treatment, confirm the diagnosis and exclude other causes:

• Rule out other causes of acute kidney injury (hypovolemia, medication toxicity, obstruction, IV contrast)
• Check serum creatinine (elevation ≥50% from baseline)
• Perform urinalysis (look for sterile pyuria, hematuria, proteinuria)
• Consider renal ultrasound to exclude obstruction
• Consider renal biopsy in severe or atypical cases to confirm diagnosis

Treatment Algorithm

Step 1: Immediate Management

• Discontinue the suspected offending agent (most commonly antibiotics, PPIs, NSAIDs) 3
• Ensure adequate hydration
• Temporarily hold immune checkpoint inhibitors if applicable 1

Step 2: Corticosteroid Therapy Based on Severity

1. Grade 1 (Creatinine 1.5-2.0× baseline):

   • Consider temporarily holding medications
   • Monitor creatinine weekly 1
   • If no improvement, treat as Grade 2

2. Grade 2 (Creatinine 2-3× baseline):

   • Prednisone 0.5-1 mg/kg/day orally 1, 2
   • Taper over 4-6 weeks if improved
   • Monitor creatinine weekly

3. Grade 3-4 (Creatinine >3× baseline or >4.0 mg/dL):

   • Methylprednisolone 1-2 mg/kg/day IV 1, 2
   • Consider pulse methylprednisolone (500-1000 mg daily for 3 days) in severe cases 4
   • Taper over at least 4 weeks once improved to Grade 1

Step 3: For Steroid-Resistant Cases

If no improvement after 1-2 weeks of corticosteroid therapy or worsening despite therapy:

• Consider additional immunosuppression with:
  • Mycophenolate mofetil 5
  • Alternative options: azathioprine, cyclophosphamide, cyclosporine 1

Monitoring and Follow-up

• Monitor serum creatinine weekly until stabilization 1, 2
• Continue monitoring during steroid taper
• Consider nephrology consultation for severe cases or those not responding to initial therapy 1

Prognostic Factors

• Early initiation of corticosteroids is associated with better renal function recovery 6
• Presence of interstitial fibrosis on biopsy indicates poorer response to steroids 6
• Neutrophilic predominance in biopsy is associated with favorable response 6

Special Considerations

• Diabetes mellitus may be associated with poorer response to steroids 6
• Avoid re-exposure to the causative agent due to high risk of recurrence 2
• For immune checkpoint inhibitor-related interstitial nephritis, permanent discontinuation of therapy may be necessary for Grade 3-4 nephritis 1

Common Pitfalls to Avoid

1. Delaying corticosteroid initiation (early treatment improves outcomes)
2. Inadequate duration of steroid therapy (taper over at least 4 weeks)
3. Failure to identify and discontinue the offending agent
4. Overlooking other potential nephrotoxic medications
5. Tapering steroids too rapidly, which may lead to relapse

Both oral prednisolone and IV pulse methylprednisolone have shown similar efficacy in treating drug-induced interstitial nephritis when used early, so the choice depends on the severity of the case 4.