Complement-Mediated Thrombotic Microangiopathy after Kidney Transplant: Should Treatment with C5 Inhibitor Be Lifelong?

Complement-mediated thrombotic microangiopathy (CM-TMA) is a rare and life-threatening complication that can occur in kidney transplant recipients, with various potential triggers including immunosuppressive medications. The optimal management and duration of treatment with C5 inhibitors (C5i) for CM-TMA in this patient population remain areas of ongoing investigation. We present the case of a 38-year-old female with a history of IgA nephropathy who underwent preemptive living-related kidney transplantation and subsequently developed CM-TMA 7 years post-transplant. Treatment with ravulizumab led to a rapid hematologic response and stabilized platelet counts. Serial measurements of complement functional tests and clinical stability guided the discontinuation of C5i therapy. The case highlights the complexity of managing CM-TMA in kidney transplant recipients, particularly in determining the appropriate duration of C5i therapy. The absence of an established protocol for discontinuation necessitates a personalized approach based on clinical and laboratory stability, absence of complement gene variants, and serial complement functional tests. Further prospective investigations are warranted to define the optimal strategies for monitoring and safely discontinuing C5i therapy in this unique patient population. This case underscores the importance of individualized care in the management of CM-TMA post-kidney transplantation, offering insights into potential criteria for therapy discontinuation.

Anticoagulation in renal replacement therapies: Why heparin should be abandoned in critical ill patients?

Extracorporeal circuits used in renal replacement therapy (RRT) can develop thrombosis, leading to downtimes and reduced therapy efficiency. To prevent this, anticoagulation is used, but the optimal anticoagulant has not yet been identified. Heparin is the most widely used anticoagulant in RRT, but it has limitations, such as unpredictable pharmacokinetics, nonspecific binding to plasma proteins and cells, and the possibility of suboptimal anticoagulation or bleeding complications, specifically in critically ill patients with acute renal failure who are already at high risk of bleeding. Citrate anticoagulation is a better alternative, being considered a standard for continuous renal replacement therapy, since it is associated with a lower risk of bleeding complications and better efficacy, even in patients with acute renal failure or liver disease. The aim of this article is to provide an updated review of the different strategies of anticoagulation in renal replacement therapies that can be implemented in critical scenarios, focusing on the advantages and disadvantages of each one and the beneficial aspects of using citrate over heparin in critical ill patients.