From the Guidelines
For a kidney transplant recipient with donor-specific antibodies and a positive flow crossmatch, I strongly recommend implementing a desensitization protocol before proceeding with transplantation, as it has been shown to reduce the risk of antibody-mediated rejection and improve graft survival. The management of such patients is crucial to prevent hyperacute and/or accelerated rejection, and a desensitization protocol can help achieve this goal.
Desensitization Protocol
The standard approach would include:
- Plasmapheresis (typically 3-5 sessions) combined with intravenous immunoglobulin (IVIG) at 100 mg/kg after each session, plus rituximab (375 mg/m² IV, single dose) 1.
- Start this regimen 2-4 weeks pre-transplant, with daily monitoring of crossmatch and DSA levels.
Post-Transplant Management
Post-transplant, use thymoglobulin induction (1.5 mg/kg/day for 3-5 days), followed by triple maintenance immunosuppression with:
- Tacrolimus (target trough 8-12 ng/mL)
- Mycophenolate mofetil (1000 mg twice daily)
- Prednisone (tapering from 30 mg to 5 mg daily over 1-3 months) 1. Continue monitoring DSA levels weekly for the first month, then monthly for 3-6 months.
Rationale
This approach addresses the immunological barrier by removing circulating antibodies through plasmapheresis, neutralizing antibodies with IVIG, depleting B cells with rituximab, and providing robust immunosuppression to prevent antibody rebound, thereby reducing the risk of antibody-mediated rejection in this high-risk transplant scenario 1.
Key Considerations
- A positive flow cytometry or AHG-CDC crossmatch against either T cell or B cell donor targets, using sera with IgG antibodies to HLA antigens, is a contraindication to transplantation 1.
- The crossmatch identifies recipient anti-donor reactivity that is associated with a poor clinical outcome 1.
From the Research
Management of Kidney Transplant Recipients with Donor-Specific Antibodies
- Desensitization protocols have been developed to overcome immunological barriers in kidney transplant recipients with donor-specific antibodies (DSAs) 2, 3, 4.
- These protocols typically involve a combination of treatments, including plasmapheresis, intravenous immunoglobulin (IVIG), rituximab, and immunosuppressive medications 2, 3, 4.
- The goal of desensitization is to reduce or eliminate DSAs, allowing for a successful kidney transplant 2, 3, 4.
- Post-transplant monitoring of DSAs is also important, as it can help identify patients at risk of antibody-mediated rejection (AMR) and guide adjustments to immunosuppressive therapy 5, 6.
Desensitization Protocols
- One study used a desensitization protocol that included calcineurin inhibitors, methylprednisolone, and mycophenolate mofetil, as well as rituximab and plasmapheresis 2.
- Another study used a protocol that included plasmapheresis, IVIG, and rituximab, with a focus on reducing DSAs to a median fluorescence intensity (MFI) value of <1000 3.
- A third study used a protocol that included anti-CD20 therapy and peritransplant apheresis, with a focus on enabling living donor kidney transplantation in patients with DSAs 4.
Outcomes and Complications
- Studies have shown that desensitization protocols can be effective in reducing DSAs and allowing for successful kidney transplantation 2, 3, 4.
- However, complications such as AMR, transplant glomerulopathy, and graft loss can still occur, particularly in patients with persistent or de novo DSAs 5, 6.
- Monitoring of DSAs and adjustment of immunosuppressive therapy can help mitigate these risks and improve long-term graft outcomes 5, 6.