Recurrence of Immune Complex and Complement-mediated Membranoproliferative Glomerulonephritis in Kidney Transplantation

Introduction: Membranoproliferative glomerulonephritis (MPGN) represents a histologic pattern of glomerular injury that may be due to several aetiologies. Few studies have comprehensively analysed the recurrence of MPGN according to the current classification system.

Methods: We collected a multicentre, retrospective cohort of 220 kidney graft recipients with biopsy-proven native kidney disease due to MPGN between 1981 and 2021 in 11 hospitals. Demographic, clinical and histologic parameters of prognostic interest were collected. The main outcomes were time to kidney failure, time to recurrence of MPGN and disease remission after recurrence.

Results: The study group included 34 complement-mediated and 186 immune complex-mediated MPGN. A total of 81 patients (37%) reached kidney failure in a median follow-up of 79 months. The main predictors of this event were the development of rejection episodes and disease recurrence. In all, 54 patients (25%) had a disease recurrence in a median of 16 months after kidney transplantation. The incidence of recurrence was higher in patients with dysproteinaemia (67%) and complement-mediated MPGN (62%). In the multivariable model, complement-mediated MPGN emerged as a predictor of recurrence. A total of 33 patients reached kidney failure after recurrence. The main determinants of no remission were early time to recurrence (<15 months), estimated glomerular filtration rate <30 mL/min/1.73 m2 and serum albumin <3.5 g/dL at the time of recurrence.

Conclusions: One-fourth of the patients with native kidney disease due to MPGN developed clinical recurrence in the allograft, especially in cases with complement-mediated disease or in those associated with dysproteinaemia. The kidney outcomes of disease recurrence with currently available therapies are heterogeneous and thus more effective and individualized therapies are needed.