Kidney Transplantation in C3 Glomerulopathy: A Case Series

Rationale & Objective C3 glomerulopathy(C3G), a form of glomerulonephritisassociated with dysregulation of the alternative complement pathway, occurs either as dense deposit disease (DDD) or C3 glomerulonephritis(C3GN). Few studies have reported outcomes of patients with C3G after transplantation since its formal classification and the advent of complement-targeting therapies such as eculizumab. Study Design Case seriesof C3G. Setting & Participants We reviewed laboratory testing, native and allograft biopsy reports, and clinical charts of the 19 patients (12, C3GN; and 7, DDD) from our C3G registry who underwent transplantation between 1999 and 2016. Results During a median follow-up of 76 months, 16 patients had recurrent disease (10 of 12, C3GN; and 6 of 7, DDD), with median time to recurrence of 14 months in C3GN versus 15 months in DDD. Graft failure was more frequent in patients with DDD (6 of 7) than in patients with C3GN (3 of 12), occurred at a median time of 42 months posttransplantation, and was attributed to recurrent disease in half the failures. A rare genetic variant or autoantibody associated with alternative complement pathwayabnormalities was detected in 9 of 10 screened patients. Treatment of 7 patients (8 allografts) with eculizumabwas associated with variable clinical outcomes. Limitations Incomplete testing for complement pathway abnormalities and genetic defects, incomplete records of HLA antigen matching, lack of centralized biopsy review, and limitedsample size. Conclusions In a case seriesof C3G transplant recipients, the proportion of disease recurrence was high in both C3GN and DDD, although graft loss appeared to occur more frequently in DDD. In a small subset of study patients, eculizumabtherapy was not consistently followed by salutary outcomes.