Atypical hemolytic uremic syndrome in kidney transplantation

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder that affects individuals of any age. It is caused by genetic abnormalities of the alternative complement pathway, arising from inherited or de novo mutations, or from acquired factors such as autoantibodies against complement proteins, including complement factor H. Clinically, aHUS is characterized by the classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. However, its clinical presentation may be difficult to distinguish from typical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. aHUS is driven by uncontrolled activation of the alternative complement pathway, leading to endothelial injury and microvascular thrombosis. Atypical HUS may also occur after kidney transplantation, either as recurrence of the native disease or as de novo post-transplant thrombotic microangiopathy. The diagnosis of post-transplant aHUS relies on the presence of the above-mentioned classic triad and the exclusion of secondary causes such as thrombotic thrombocytopenic purpura and Shiga toxin-associated HUS. The pathophysiology is similar, involving either genetic mutations affecting complement proteins or acquired dysregulation due to autoantibodies. Historically, plasma exchange was used to replace dysfunctional complement regulators and remove circulating autoantibodies, with variable success. After transplantation, the disorder may either recur or develop de novo. In the past, plasmapheresis was considered beneficial. More recently, the availability of eculizumab, an anti-C5 monoclonal antibody that inhibits terminal complement activation, has become the treatment of choice, either as monotherapy or with plasma exchange. However, uncertainties remain regarding the optimal duration and dosing of long-term therapy, particularly in transplant recipients.