What is the treatment for kidney transplant rejection?

Treatment for Kidney Transplant Rejection

Corticosteroids are the first-line treatment for acute cellular rejection in kidney transplants, followed by lymphocyte-depleting antibodies for steroid-resistant cases, while optimizing maintenance immunosuppression regimens to prevent further rejection episodes. 1

Diagnostic Approach Before Treatment

• A kidney allograft biopsy is strongly recommended before initiating treatment for acute rejection, unless the biopsy would substantially delay necessary treatment 1
• Monitoring for rejection should include:
  • Regular serum creatinine measurements
  • Urine protein excretion assessment
  • Calcineurin inhibitor (CNI) blood levels
  • Kidney ultrasound examination as part of allograft dysfunction assessment 1

Treatment Algorithm for Kidney Transplant Rejection

1. Acute Cellular Rejection (T-cell mediated)

First-line treatment:

• High-dose corticosteroids (methylprednisolone 500mg IV daily for 3 days) 1, 2
• For patients not on maintenance steroids, add or restore maintenance prednisone 1
• Success rate of steroid therapy: approximately 60-70% 2

For steroid-resistant rejection (no response by day 5):

• Lymphocyte-depleting antibodies (anti-thymocyte globulin or OKT3) 1, 2
• Alternative: Switch from cyclosporine to tacrolimus (success rate ~60%) 2
• Consider mycophenolate mofetil (MMF) for interstitial rejection types 2
  • MMF has shown 68% reduction in recurrent rejection episodes 3

2. Antibody-Mediated Rejection (AMR)

• Plasmapheresis to remove circulating antibodies 2
• Intravenous immunoglobulin (IVIG) 2
• Consider rituximab (anti-CD20) for B-cell depletion
• Optimize maintenance immunosuppression

Maintenance Immunosuppression Optimization

After treating rejection, adjust maintenance immunosuppression:

• Increase CNI target levels
• Add or increase steroid dosage
• Add mycophenolate mofetil if not already prescribed 1, 2
• Consider switching from cyclosporine to tacrolimus 1
• For patients with CNI toxicity and declining function, consider:
  • Reducing, withdrawing, or replacing the CNI 1
  • Belatacept as an alternative to CNIs for preserving kidney function 4

Monitoring After Rejection Treatment

• Frequent monitoring of serum creatinine
• Regular assessment of CNI blood levels
• Monitor for drug-related adverse effects
• Adjust immunosuppressive medications to achieve target levels 1
• Screen for opportunistic infections (especially if lymphocyte-depleting agents were used)

Important Considerations and Pitfalls

• Steroid resistance: Don't assume steroid resistance before day 5 of treatment unless vascular rejection features are present 2
• Infection risk: Balance aggressive immunosuppression with increased risk of infections and malignancy 2
• Drug toxicity: High-dose steroid therapy exceeding 3-5g total methylprednisolone may not provide additional benefit but increases complication risks 5, 6
• Recurrent rejection: Patients with history of rejection are at higher risk for subsequent episodes and poorer long-term outcomes 3
• Differential diagnosis: Always consider other causes of graft dysfunction (CNI toxicity, BK virus nephropathy, recurrent disease) 2

Prevention of Recurrent Rejection

• Adding MMF to maintenance therapy after initial rejection episode reduces recurrent rejection risk by up to 68% 3
• Maintain appropriate CNI levels through regular monitoring 1
• Consider long-term prednisone maintenance in patients with rejection history 1