Complement related kidney diseases: Recurrence after transplantation

Abstract

The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials.

Keywords: Kidney disease recurrence, Complement dysregulation, Atypical hemolytic uremic syndrome, C3 glomerulopathies, Dense deposit disease, Plasma therapy, Eculizumab, C3 glomerulonephritis

Core tip: Complement cascade is an important pathway of several kidney diseases. A distinction should be made between kidney diseases with complement overactivation and those with complement dysregulation. The latter are related to congenital or acquired abnormalities of complement factors. These diseases are linked to constitutional abnormalities of the patients, have high recurrence rate after renal transplantation and represent an important cause of graft loss. Diagnosis and treatment are not easy to be made. Just in the last decade a growing knowledge in the field of genetic and biology allowed the complement inhibitors to be the first class drug in the treatment.