What is the treatment approach for Granulomatous interstitial nephritis (GIN)?

Treatment Approach for Granulomatous Interstitial Nephritis (GIN)

The first-line treatment for granulomatous interstitial nephritis should be corticosteroid therapy after identifying and removing the underlying cause, particularly if it is drug-induced or idiopathic in nature. 1, 2, 3

Etiology Identification

Before initiating treatment, it is crucial to identify the underlying cause of GIN:

1. Common causes to investigate:

   • Medications: Antibiotics (cephalosporins, vancomycin, nitrofurantoin, ciprofloxacin, doxycycline), NSAIDs 1, 4
   • Systemic diseases: Sarcoidosis, tuberculosis, fungal infections, granulomatosis with polyangiitis 2, 5
   • Other conditions: SLE, IgA nephropathy 2
   • Idiopathic: Accounts for approximately 18% of GIN cases in native kidneys 5

2. Diagnostic workup:

   • Kidney biopsy (essential for definitive diagnosis)
   • Evaluation for tuberculosis (especially in endemic areas)
   • Evaluation for sarcoidosis (calcium metabolism, vitamin D levels)
   • Medication history review
   • Assessment of tubular atrophy and interstitial fibrosis to determine prognosis 1

Treatment Algorithm

Step 1: Address the Underlying Cause

• Drug-induced GIN: Discontinue the offending agent immediately 1, 4
• Infectious GIN:
  • Tuberculosis: Appropriate anti-tuberculous therapy 2
  • Fungal infections: Antifungal treatment
• Sarcoidosis: Corticosteroid therapy 3, 5
• Autoimmune diseases: Disease-specific immunosuppression

Step 2: Corticosteroid Therapy

• Indications: Drug-induced GIN, sarcoidosis-related GIN, idiopathic GIN 3
• Regimen:
  • Initial: Oral prednisone 1 mg/kg/day (maximum 80 mg) 6
  • Consider IV pulse methylprednisolone (500-1000 mg daily for 3 days) for severe cases 6
  • Gradual taper over 3-6 months based on clinical response 6

Step 3: Alternative Immunosuppression (for steroid-resistant cases)

• Options:
  • Mycophenolate mofetil (MMF) 6
  • Cyclophosphamide (for severe cases) 6
  • Azathioprine (1-2 mg/kg/day) 6

Step 4: Supportive Care

• Management of renal dysfunction:
  • ACE inhibitors or ARBs for proteinuria >0.5 g/day 7
  • Blood pressure control (target <130/80 mmHg) 7
  • Dietary sodium restriction (<2.0 g/day) 6
  • Appropriate diuretic therapy for edema 6

Monitoring and Follow-up

• Regular assessment of renal function (serum creatinine, eGFR)
• Monitoring of proteinuria
• Urinalysis to assess for persistent hematuria or pyuria
• Adjustment of immunosuppression based on clinical response
• Monitoring for medication side effects

Special Considerations

1. Poor response to steroids: Consider reviewing the diagnosis, especially to rule out infectious causes like tuberculosis 5

2. Severe renal dysfunction: Patients presenting with severe renal impairment may require dialysis; early treatment improves chances of renal recovery 2

3. Prognosis factors:

   • Extent of tubular atrophy and interstitial fibrosis on biopsy 1
   • Timing of treatment initiation (earlier treatment generally yields better outcomes)
   • Underlying etiology (drug-induced GIN typically has better outcomes than other causes when the offending agent is promptly discontinued) 4

4. Long-term follow-up: Some patients may develop chronic kidney disease despite appropriate treatment, requiring ongoing nephrology care 2

Common Pitfalls to Avoid

1. Delayed diagnosis: GIN is rare (0.5-0.9% of renal biopsies) and may be missed without appropriate histopathological evaluation 1

2. Failure to identify and remove the offending agent: Particularly important in drug-induced cases 4

3. Misdiagnosis: Incorrectly attributing GIN to sarcoidosis or tuberculosis when it is drug-induced can lead to inappropriate treatment and progression to end-stage renal disease 4

4. Inadequate duration of therapy: Premature discontinuation of corticosteroids may lead to relapse

5. Overlooking infectious causes: Initiating immunosuppression without ruling out infectious etiologies (especially tuberculosis) can worsen outcomes 5