What is the treatment for suspected kidney rejection?

Treatment of Suspected Kidney Rejection

Corticosteroids are the recommended first-line treatment for acute cellular rejection in kidney transplant recipients, with biopsy confirmation strongly preferred before initiating therapy unless it would substantially delay treatment. 1

Diagnostic Approach Before Treatment

Obtain a kidney allograft biopsy before treating acute rejection unless the biopsy will substantially delay treatment. 1 This is critical because:

• Multiple conditions mimic rejection including calcineurin inhibitor (CNI) toxicity, polyoma nephritis, recurrent glomerulonephritis, and prerenal/postrenal failure 2
• The biopsy must be of adequate size to make an accurate diagnosis 2
• Persistent, unexplained increases in serum creatinine warrant biopsy 1
• If serum creatinine has not returned to baseline after rejection treatment, repeat biopsy is suggested 1

First-Line Treatment: Corticosteroids

Administer pulse methylprednisolone 0.25-1.0 g intravenously for 3-5 doses as initial therapy. 1, 3, 2 This approach has a 60-70% success rate. 2

• Oral prednisone (250 mg) may be equally efficacious as an alternative 2
• Do not assume steroid resistance before day 5 of treatment, though vascular rejection on histology may warrant earlier escalation 2
• For patients not on maintenance steroids who experience rejection, add or restore maintenance prednisone 1

Second-Line Treatment: Steroid-Resistant Rejection

For acute cellular rejections that do not respond to corticosteroids or for recurrent acute cellular rejections, use lymphocyte-depleting antibodies (such as anti-thymocyte globulin) or OKT3. 1

The evidence supports:

• Polyclonal or monoclonal antilymphocytic antibodies have 60-70% success rates in steroid-resistant rejection 2
• Anti-thymocyte globulin (ATGAM) administered at 10-15 mg/kg/day for 14-21 doses has demonstrated efficacy for steroid-resistant rejection 4
• Balance potential benefits against risks of infection and lymphoma 2

Alternative and Adjunctive Therapies

Immunosuppression Optimization

After any rejection episode, intensify baseline immunosuppression: 2

• Increase CNI (cyclosporine or tacrolimus) target levels 2
• Add or increase steroid dosage 2
• Add mycophenolate mofetil (particularly effective for interstitial/cellular rejection) 2
• Consider switching from cyclosporine to tacrolimus (approximately 60% success rate for recurrent or antibody-resistant rejection) 2

Antibody-Mediated Rejection (AMR)

For refractory AMR, consider: 5, 6

• Plasmapheresis combined with intravenous immunoglobulin 5, 6, 2
• Rituximab (anti-CD20 therapy) for cases with CD20+ B-cell infiltrates refractory to steroids and antithymocyte globulin 5
• Eculizumab (anti-C5 monoclonal antibody) as salvage therapy for severe AMR resistant to conventional treatment, particularly in cases with C1q-fixing donor-specific antibodies 7, 6

Emerging Therapies

• Photopheresis has shown promise for refractory rejection, with immunomodulatory effects directed at donor-specific T-cell clones without generalized immunosuppression 8

Critical Monitoring After Treatment

Measure serum creatinine and CNI blood levels frequently after initiating rejection therapy: 1

• CNI levels should be checked whenever there is decline in kidney function that may indicate nephrotoxicity or rejection 1
• If creatinine does not return to baseline after rejection treatment, obtain repeat biopsy 1
• Monitor for new-onset or unexplained proteinuria >3.0 g per gram creatinine as indicator of glomerular injury 7

Common Pitfalls to Avoid

• Do not delay biopsy unnecessarily - treating empirically without histologic confirmation risks inappropriate therapy and missed alternative diagnoses 1, 2
• Do not assume steroid resistance prematurely - allow full 5-day course unless vascular rejection is present on biopsy 2
• Do not continue escalating therapy indefinitely - balance benefits against serious risks including infection, lymphoma, and steroid-related complications (19 deaths from steroid complications in one series) 3, 2
• Do not forget to intensify maintenance immunosuppression - any rejection episode should trigger increased baseline therapy to prevent recurrence 2