Histological predictors of outcome in C3 glomerulopathy and idiopathic immunoglobulin-associated membranoproliferative glomerulonephritis

Background and objectives C3 glomerulopathy and idiopathic immunoglobulin-associated membranoproliferative glomerulonephritis (Ig-MPGN) are kidney diseases characterised by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients reach end stage kidney disease within 10 years. Design, setting, participants and measurements To improve identification of patients with poor prognosis we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histological scoring system, we analysed 156 native diagnostic kidney biopsies from a retrospective cohort of 123 patients with C3 glomerulopathy and 33 patients with Ig-MPGN. We used linear regression, survival analysis and Cox proportional hazards models to assess the relationship between histological and clinical parameters with outcome. Results Frequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane (GBM) double contours and endocapillary hypercellularity. Multivariable analysis showed negative associations between estimated glomerular filtration rate (eGFR) and crescents, interstitial inflammation, and interstitial fibrosis and tubular atrophy (IFTA). Proteinuria positively associated with endocapillary hypercellularity and GBM double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at time of biopsy, and cellular/fibrocellular crescents, segmental sclerosis and IFTA scores. Conclusions Our detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and IFTA scores were significant determinants of deterioration in kidney function