Abstract: FR-PO760
Post-Transplant Thrombotic Microangiopathy: A Miraculous Outcome with Eculizumab and Belatacept
Session Information
- Post-Transplantation and Case Reports
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Capistrano, Maria Christina Victoria M., Tufts Medical Center, Boston, Massachusetts, United States
- Agarwal, Krishna A., Tufts Medical Center, Boston, Massachusetts, United States
Introduction
Post-transplant TMA is a rare but devastating complication, often resulting in graft loss. Calcineurin-inhibitors, antibody-mediated rejection and complement pathway mutations are commonly implicated but the diagnosis is often challenging. We present a case of TMA highlighting these diagnostic challenges.
Case Description
A 57-year-old woman with ESKD from reflux nephropathy underwent her 3rd deceased donor kidney transplant (prior grafts failed from chronic AMR, cPRA 100%, KDPI 1%, rATG for induction and tacro/MMF/pred maintenance), complicated by delayed graft function. On post-op day 6, she developed microangiopathic hemolytic anemia, thrombocytopenia, and a kidney biopsy with focal TMA, 10% cortical necrosis, and negative C4d. HLA testing revealed persistent preformed low-level B44 and new Bw4 DSAs (MFI 3537). Plasmapheresis x 5, IVIG and rituximab were employed for AMR and tacrolimus was switched to cyclosporine. A repeat biopsy on day 14 for persistent DGF revealed diffuse TMA with 50% cortical necrosis and negative C4d/SV40. DSAs were at lower levels. Eculizumab was started and cyclosporine switched to sirolimus. MMF was switched to azathioprine for severe diarrhea, but this caused severe pancytopenia. Antimetabolites were stopped and she started belatacept 5 weeks post-transplant. She made urine shortly thereafter and came off dialysis by week 6. An aHUS panel returned with CFH mutation. She continues belatacept, eculizumab and prednisone (5mg daily) with creatinine 1.2 (eGFR 50), now 100 days post-transplant.
Discussion
We present a challenging case with multiple causes of TMA acting in combination on a background of CFH gene mutation. While eculizumab is commonly used for complement-related TMA, experience with belatacept is limited. The treatment of calcineurin-inhibitor induced TMA is withdrawal of the offending agent but there may be refractory cases like ours. A regimen of belatacept and the mTOR inhibitor, sirolimus, resulted in rapid improvement in graft function in our patient. While AMR was probably contributing to the TMA, treatment with lowering of DSA levels did not immediately improve graft function. Testing for complement pathway mutation is not readily available and has a long turnaround time. But this should not deter physicians from sending this as it is a valuable guide for continued use of eculizumab.