Can low serum complement be used as an indicator of thrombotic microangiopathy in kidney transplant candidates with unknown diagnosis?

Many patients reach kidney failure with unknown or misdiagnosed primary kidney disease. This is a major clinical issue because some native diseases, including complement-mediated thrombotic microangiopathy (TMA) and atypical hemolytic uremic syndrome (aHUS), can recur after transplant and lead to accelerated graft failure if left untreated.1,2 Complement-mediated TMA and aHUS can also precipitate progression to kidney failure in patients with other kidney diseases, such as hypertensive nephropathy, various types of glomerulonephritis, systemic immune diseases, or monoclonal gammopathies.1 Recognizing patients at risk of this condition is important as it affects their suitability for transplantation (eg, risk of complement-mediated TMA/aHUS in living-­related donors) and their clinical management.2 Of note, although post-transplant complement-mediated TMA/aHUS recurrence can be effectively controlled by complement-targeting therapies,2,3 the efficacy of complement blockade critically depends on early treatment initiation.2,4 Hence, recognizing patients at risk of having had undiagnosed complement-mediated TMA/aHUS may significantly impact the outcomes of transplant candidates and patients undergoing kidney transplantation