C32-27 When Complement Turns Culprit: A Case of Post-transplant Thrombotic Microangiopathy

Abstract Atypical hemolytic uremic syndrome (aHUS) is a rare form of complement-mediated thrombotic microangiopathy (CM-TMA) with a prevalence of 5 cases per 1 million in general population, and poses diagnostic and therapeutic challenges. If untreated, 33%-40% of patients may progress to end-stage renal disease (ESRD), and up to 48% can develop neurological or cardiovascular complications. In post-transplant patients, CM-TMA has been reported in 0.8% to 14% of cases. We report a case of CM-TMA in a 65-year-old female with end-stage renal disease in her transplant kidney secondary to BK nephropathy, maintained on tacrolimus. The patient was admitted for severe acute kidney injury and encephalopathy, complicated by thrombocytopenia, progressive encephalopathy and melena requiring multiple blood product transfusions. The esophagogastroduodenoscopy revealed multiple arteriovenous malformations (AVMs) with no active bleeding. Given the triad of uremia, thrombocytopenia, and acute kidney injury, TMA was suspected. Laboratory evaluation revealed a low ADAMSTS13, elevated lactate dehydrogenase (LDH), and low haptoglobin. Although schistocytes were not observed on peripheral smear, additional laboratory studies indicated activation of the alternative complement pathway. Tacrolimus was discontinued and she was started on Eculizumab. Once stabilized, tacrolimus was restarted at a low dose, and she received an additional dose of eculizumab. After a 24-day hospital stay, she was discharged with multidisciplinary follow-up. In aHUS, uncontrolled inflammation from dysregulated complement activation causes severe vascular endothelial injury, particularly in the kidneys. The triggers associated with its development can be bacterial and viral infections, cancer, pregnancy, and certain medications including Tacrolimus. aHUS can also be caused by genetic variations in complement regulators such as loss of function mutation in complement factor H, complement factor I, cluster of differentiation 46 (CD46) and thrombomodulin (THBD), or gain of function mutation in complement factor B and C3 genes. Eculizumab binds to complement protein C5, inhibiting its cleavage into C5a and C5b, preventing the membrane attach complex (MAC) formation responsible for inflammation and cell damage. This case illustrates the importance of rapid diagnosis and treatment of CM-TMA as potential complications can be severe and irreversible. Due to its mechanism as a complement inhibitor, it is crucial to rule out any active infections, particularly from encapsulated organisms such as Neisseria before eculizumab initiation. Clinicians may often find themselves walking a diagnostic tightrope as some infectious workups require prolonged turnaround times, necessity balance between timely treatment and patient safety. This abstract is funded by: None