Abstract
BACKGROUND: We here report on the first observation of a C3 mutation that is related to atypical hemolytic and uremic syndrome (aHUS), which occurred in a pancreatic islet transplant patient. Immunosuppressive treatments, such as calcineurin inhibitors, have been linked to undesirable effects like nephrotoxicity. CASE PRESENTATION: A 40-year-old man with brittle diabetes, who was included in the TRIMECO trial, became insulin-independent 2 months after pancreatic islet transplantation. About 15 months after islet transplantation, the patient exhibited acute kidney injury due to aHUS. Despite plasma exchange and eculizumab treatment, the patient developed end-stage renal disease. A genetic workup identified a missense variant (p.R592Q) in the C3 gene. In vitro, this C3 variant had defective Factor I proteolytic activity with membrane proteins as cofactor proteins, which was thus classified as pathogenic. About 1 year after the aHUS episode, kidney transplantation was carried out under the protection of the specific anti-C5 monoclonal antibody eculizumab. The patient had normal kidney function, with preserved pancreatic islet function 4 years later. CONCLUSIONS: Pancreatic islet transplantation could have triggered this aHUS episode, but this link needs to be clarified. Although prophylactic eculizumab maintains kidney allograft function, its efficacy still needs to be studied in larger populations.