A Case of Mutation Negative Transplant Associated Thrombotic Microangiopathy Successfully Treated With Eculizumab
- Transplantation: Clinical - Case Reports
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
- 2002 Transplantation: Clinical
- Murari, Ujjwala, Newark Beth Israel Medical Center, Newark, New Jersey, United States
- Thimmareddygari, Divya Mounisha Reddy, Newark Beth Israel Medical Center, Newark, New Jersey, United States
- Nandigam, Purna Bindu, Cooperman Barnabas Medical Center, Livingston, New Jersey, United States
- Khan, Umair, Newark Beth Israel Medical Center, Newark, New Jersey, United States
Transplant associated Thrombotic Microangiopathy (TA-TMA) is rare and causes graft failure. TMA may occur de-novo, triggered by immunosuppressive medication and antibody mediated rejection (AMR). We present a rare case of TA-TMA due to Atypical HUS (aHUS) successfully treated with Eculizumab.
A 45-year-old female with history of end-stage renal disease of unclear etiology underwent a renal transplant with Thymoglobulin induction. A pre-transplant work up showed negative CDC cross match, zero percent PRA, and 2A-2B-0DR HLA mismatch. Post-operative course was complicated by persistently high creatinine, hemolytic anemia, thrombocytopenia, elevated LDH, and low haptoglobin by day 3. Given the possibility of Calcineurin inhibitor induced TMA, Tacrolimus was changed to Everolimus and the patient received plasmapheresis/hemodialysis. Allograft biopsy confirmed TMA without concurrent rejection. Disseminated intravascular coagulation was ruled out with a normal prothrombin and partial thromboplastin time. With poor response to Everolimus, a repeat allograft biopsy was done which showed prior findings. A negative workup for infection, ADAMTS13, complement genetic mutation panel, complement levels with above findings pointed towards atypical HUS induced by renal transplant and Tacrolimus. Everolimus was switched to Belatacept and Eculizumab. A significant improvement in her renal function following Eculizumab therapy was noted in the subsequent weeks.
Incidence of renal transplant associated TMA is around 0.8-1.4%. It’s often seen in the first week of post-transplant course when patients receive high doses of immunosuppressive medications. Often mutations in complement regulating or alternate pathway enhancing proteins or the presence of anti-factor H antibodies can predispose a patient to aHUS(1). Complement mutations are not seen in 30% cases.Upon literature review, a few cases with Plasma exchange resistant aHUS were successfully treated with Eculizumab, but had complement mutations, unlike our patient.
MAC complex or C5b-9can be used as a marker to monitor complement inhibition. Given the rarity, there are no guidelines regarding the dose and duration of therapy with Eculizumab; relapses and renal complications often direct the duration (2) and is an area of ongoing research.