Comprehensive Analysis of Thrombotic Microangiopathy Following Renal Transplantation

Background: Thrombotic microangiopathy is a severe complication of renal transplantation. Little is known about risk factors, incidence of autoantibodies against complement components, and prognosis. Methods: Clinical and laboratory data were retrospectively collected for 13 patients diagnosed with post-transplant thrombotic microangiopathy (PT-TMA) in 2011-2018. Enzyme-linked immunosorbent assay (ELISA) results were compared to transplant recipients without PT-TMA and healthy controls. Results: Nine patients (69%) had potential PT-TMA risk factors other than exposure to calcineurin inhibitors (CNIs). Stratification by time to PT-TMA yielded two groups. Patients diagnosed within 6 months of transplantation (n = 6) were characterized by positive donor-specific antibody (DSA) test, complement-associated renal disease, and acute rejection. Two had IgG and IgA autoantibodies to complement Factors H and I, respectively. Patients diagnosed ≥ 3 years after transplantation (n = 7) had a high rate of infection. Renal biopsy yielded dense deposits in 6 patients, and only one with primary immune complex renal disease. Within 2 years, graft failure requiring dialysis occurred in 6 patients (46%). Three patients with early-onset PT-TMA showed improved renal function and remained stable under eculizumab treatment. Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (EPTLD) developed in 3 patients, 2 of whom had received eculizumab for more than 5 years. Five patients (39%) died during follow-up. Conclusion: In this study, PT-TMA was associated with other risk factors besides CNI exposure, with differences by time of onset from transplantation. Prognosis was generally poor but better for early-onset PT-TMA managed with eculizumab. The development of late EPTLD in 3 patients raises concerns.