Postkidney Transplant Thrombotic Microangiopathy Effectively Treated with Eculizumab in a Tertiary Care Center

Background: Post-transplant thrombotic microangiopathy (PT-TMA) after kidney transplant is associated with a high risk of graft loss. Terminal complement pathway inhibition by anti-complement C5 antibody (eculizumab) effectively treats post-transplant TMA after kidney transplant related to complement disorders. Initial evaluation of PT-TMA is limited by the lack of availability of complement pathway analysis, including genetic tests. Methods: We reviewed the charts of patients with PT-TMA treated with eculizumab at our center. Ten patients were identified. PT-TMA was defined as hemolytic anemia, schistocytes on peripheral smear, thrombocytopenia, and acute allograft dysfunction. Renal response was defined as eGFR>15 ml/min/1.73m2 and dialysis independence. Complete renal response was defined as eGFR>45 ml/min/1.73 m2. Results: PT-TMA was diagnosed within a week (median 2.75 days) of kidney transplant in 7 out of 10 patients. Kidney biopsy was performed on 9 patients; 8 patients showed signs of acute TMA without evidence of active rejection. Genetic analysis was done in 5 patients. One patient had a pathogenetic variant in the CFHR1 gene. Eculizumab was started within 1-3 days after diagnosis in all patients. After a median of 9 days from diagnosis, platelets persistently improved to >150 X 109/L in all patients. Haptoglobin and lactate dehydrogenase levels improved after a median of 2 weeks. After a median last follow up of 35.2 months, renal response was noted in 8 out of 10 patients. Four patients had complete renal response. Six patients were started on belatacept after discontinuing tacrolimus, considering it as a potential trigger of PT-TMA. Conclusion: Patients with early de-novo PT-TMA treated with eculizumab within 1-3 days of diagnosis had prompt hematological remission. All but two patients with late PT-TMA had improved kidney allograft function. PT-TMA after kidney transplant develops from different triggers in predisposed individuals, which are often indiscernible on immediate evaluation. Prompt eculizumab therapy may benefit PT-TMA irrespective of etiology, especially those developing early post-transplant, suggesting the role of complement activation. A prospective study on the effectiveness of eculizumab in treating PT-TMA from different etiologies is important to inform further practice.