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.