#1011 Clinical characteristics and outcomes of C3 glomerulopathy and immune complex MPGN from the UK National Registry of Rare Kidney Diseases (RaDaR)
Authors: Masoud Sherry , Downward Lewis , Wong Katie , Webb Nicholas , Proudfoot Clare , Wong Edwin , Gale Daniel P 
Published: May 2024

Abstract

Background and Aims
Primary membranoproliferative glomerulonephritis (MPGN), is a rare kidney disorder which can be further divided into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on relative complement and immunoglobulin staining on biopsy specimens. There is limited literature on the natural history and long-term outcomes of this disorder. The aims of this study were to:

Method
Adult and paediatric patients with diagnostic biopsy reports that could be classified or reclassified as C3G or IC-MPGN within RaDaR were included. RaDaR contains data on MPGN patients from kidney units across the UK, with automated collection of retrospective and prospective laboratory data. Follow-up time was from diagnosis, defined by biopsy date, until KF, death or last available test result. Kidney failure was defined as initiation of dialysis, kidney transplantation or sustained eGFR ≤15 mL/min/1.73 m2 for ≥4 weeks. Annualized rate of eGFR loss (eGFR slope) was calculated for the first 24 months and over full duration of follow-up. A linear mixed model was used to estimate each patient's intercept and slope of eGFR using a minimum of four observations. Analyses of time to KF were conducted using Kaplan–Meier estimates with log-rank tests for comparisons and Cox regression. The latter was used to investigate the association of early (within 24 months of diagnosis) changes in urine protein:creatinine ratio (UPCR), eGFR and eGFR slope with KF events over maximum of 20 years.

Results
Our cohort included 135 patients with C3G and 152 patients with IC-MPGN diagnosed between 1987 and 2020. At the time of diagnosis 153/287 (53%) of the cohort were paediatric (&lt;18 years old). Both groups had significant proteinuria at baseline (Table 1). Median eGFR was 70 mL/min/1.73 m2 (IQR 30-92) and 58 mL/min/1.73 m2 (IQR 40-110) for C3G and IC-MPGN respectively. Median time to KF was 9.3 years for C3G and 12 years for IC-MPGN but the difference was not statistically significant (p = 0.31). KF was significantly associated with changes in UPCR between 0-12 months and 6-12 months (HRs adjusted for eGFR) (Fig. 1). Similarly, a 50 mg/mmol reduction in time-averaged UPCR between 0-12 months and 6-12 months was also strongly associated with a lower risk of KF (HR adjusted for eGFR [95% Confidence Interval] 0.66 [0.53-0.83] and 0.71 [0.59-0.85] respectively). Both annualized 24 month eGFR slope, and percentage change in eGFR at 24 months were also significantly associated with KF events (Fig. 1).

Conclusion
We present one of largest studies describing the demographics, clinical characteristics, and long-term outcomes of 287 UK patients with IC-MPGN and C3G. Consistent with other studies we found no statistically significant difference in time to KF for C3G and IC-MPGN patients. We also demonstrate the value of short-term changes in proteinuria and eGFR (within 24 months of biopsy diagnosis), for predicting long-term risk of kidney failure.