What is the management of immunotherapy-related nephritis?

Management of Immunotherapy-Related Nephritis

The management of immunotherapy-related nephritis requires prompt recognition, grading of severity, and appropriate immunosuppressive therapy, with corticosteroids as the cornerstone of treatment.

Diagnosis and Assessment

• Immunotherapy-related nephritis typically presents as acute interstitial nephritis (AIN) in 80-90% of cases, though glomerular disease can also occur 1
• Monitor serum creatinine prior to every dose of checkpoint inhibitor therapy 1
• Evaluate for alternative causes of acute kidney injury:
  • Recent IV contrast administration
  • Dehydration
  • Concomitant nephrotoxic medications (especially PPIs and NSAIDs)
  • Urinary tract infection 1
• Median time to onset is 14 weeks (range: 6.5-21 weeks) 1

Grading and Management

Grade 1 (Creatinine 1.5-2.0× baseline or >0.3 mg/dL increase)

• Consider temporarily holding immune checkpoint inhibitor (ICI) 1
• Monitor creatinine weekly 1
• Ensure adequate hydration 2

Grade 2 (Creatinine 2-3× baseline)

• Hold ICI temporarily 1
• Consult nephrology 1
• Administer prednisone 0.5-1 mg/kg/day 1, 2
• If improved to Grade 1 or less, taper corticosteroids over 4-6 weeks 1
• If worsening or no improvement after 1 week, increase to 1-2 mg/kg/day prednisone and permanently discontinue ICI 1

Grade 3-4 (Creatinine >3× baseline or >4.0 mg/dL; life-threatening)

• Permanently discontinue ICI therapy 1
• Consult nephrology urgently 1
• Administer high-dose corticosteroids (methylprednisolone 1-2 mg/kg/day IV) 1, 2
• Consider pulse methylprednisolone (500-1000 mg daily for 3 days) in severe cases 2
• If improved to Grade 1, taper corticosteroids over at least 4 weeks 1
• If no improvement after 3-5 days or worsening, consider additional immunosuppression (infliximab, azathioprine, cyclophosphamide, cyclosporine, or mycophenolate mofetil) 1

Important Considerations

• Kidney biopsy is typically not necessary unless AKI is refractory to steroids 1
• Reflex kidney biopsy should be discouraged until steroid treatment has been attempted 1
• Swift treatment of the autoimmune component is crucial for recovery 1
• Recent data suggest the incidence of renal immune-related adverse events may be higher than initially reported (9.9-29%) 1
• Patients who develop multiple immune-related adverse events may have worse outcomes 3
• Monitor creatinine weekly until stabilization and continue monitoring during steroid taper 2

ICI Rechallenge Considerations

• 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
• For Grade 3-4 nephritis, permanent discontinuation of ICI therapy is generally recommended 1, 2
• Recent evidence suggests rechallenge with immunotherapy after kidney immune-related adverse events may be possible in select patients but requires careful individual evaluation 3

Special Considerations

• Patients with renal allografts are at high risk of rejecting the transplanted kidney with PD-1 pathway blockers 1
• Concomitant medications, especially PPIs and NSAIDs, may contribute to the development of AIN during ICI therapy 4
• Discontinuation of potentially nephrotoxic concomitant medications is essential for management 4

By following this structured approach to the management of immunotherapy-related nephritis, clinicians can optimize patient outcomes while minimizing long-term renal damage.