#1640 Alternative complement pathway disorders in the transplant setting—experience from a large volume center

Abstract

Abstract Background and Aims Complement alternative pathway disorders, atypical hemolytic-uremic syndrome (aHUS) and C3 glomerulopathy (C3G), are rare diseases with a high rate of recurrence after kidney transplantation. Due to limited availability of testing, patients may go undiagnosed, indicating testing during pretransplant evaluation. Posttransplant thrombotic microangiopathy (TMA) is a rare complication of transplantation. A large number of post transplant TMAs is regarded as secondary, either to immunosuppressive drugs or transplant itself. In select cases, complement alternative pathway disorders analysis is warranted. Method We retrospectively reviewed all patients in whom complement system diagnostic work-up was performed in the transplant setting in our center, from 2017 to 2022. Complement system analysis in isolated histological TMA of the allograft, without extrarenal manifestations and with known cause of native kidneys ESRD, was not performed routinely. Patients in whom alternative pathway disorders were confirmed were compared with those with no abnormalities detected by complement system analysis. Results 12 patients were identified, 75% male, median age 39.5 years (IQR 28-60.25). 8 patients were evaluated before transplantation. 4 of the 8 patients were referred for transplantation with diagnosed aHUS. Genetic testing was used for recurrence risk stratification. In living donor transplantations 2 donors were tested as well. One patient was referred from a neighboring resource poor country and was not on eculizumab therapy. He was homozygous for a high risk causative mutation. He was declined for living related donor kidney transplant, due to risk to the donor and unavailability of eculizumab. Compassionate use request was initiated. One patient was referred as possible C3G and repeat complement analysis revealed elevated C3Nef. Out of 3 patients, previously diagnosed as CKD of unknown origin or immune complex-mediated membranoproliferative glomerulonephritis, 2 were diagnosed during pretransplant evaluation: one as C3G and the other as aHUS. 4 patients were evaluated posttransplant. One analysis was performed due to recurrent C3G of the allograft, with confirmed competent dysregulation. 2 analyses were in liver transplant recipients, both with systemic TMA. Severe overactivation with consumption of complement was proven in one and treated with eculizumab. The characteristics of patients with diagnosed disorders of the complement system and those without are shown in Table 1. Conclusion Transplant physicians should keep a high volume of suspicion for complement dysregulation disorders, both during the pretransplant work-up and when evaluating TMA and recurrent GN posttransplant. Special caution should be advised when a patient is referred as chronic GN, MPGN or unknown cause ESKD at a young age.