Fibrillary glomerulonephritis: an observational study of clinical-pathological features and outcomes in patients from a multi-institutional cohort

ABSTRACT Background Fibrillary glomerulonephritis (FGN) is a rare glomerulopathy characterized by randomly arranged fibrils within the mesangium and glomerular basement membrane. It has poor renal outcomes and no specific treatment. This retrospective study aimed to identify clinical-pathological predictors of outcomes in a multi-institutional cohort with histopathology performed at a single centre in the UK. Methods Patients with biopsy proven FGN between 2015 and 2024 were identified using the Cambridge University Hospitals (CUH) histopathology database. Clinical data, including demographics, comorbidities, laboratory parameters, treatments and outcomes, were compared with findings from four other studies. Histological characteristics and DNAJB9 staining, where available, were analysed. Results Thirty-five patients with FGN (2.8:1 female-to-male ratio) with a mean age of 62.8 years were identified. Autoimmune diseases, diabetes mellitus (DM) and malignancy (solid organ and haematological) were present in 28.5%, 34.2% and 20%, respectively. Nephrotic-range proteinuria was present in 58.8% and renal dysfunction in 91.4% at presentation. The most common histological pattern was mesangial proliferative/sclerosing followed by diffuse proliferative (DPGN). DNAJB9 staining was positive in all 13 tested patients. At a median 39 months follow-up, 51% progressed to end-stage renal disease (ESRD). Female sex, proteinuria and DPGN were significant predictors of ESRD on multivariate analysis. Although rituximab was associated with non-progression of disease, immunosuppression showed no statistically significant impact on outcomes. Conclusion FGN is strongly associated with malignancy, autoimmune disease and DM. Prognosis remains poor, with progression to ESRD significantly influenced by proteinuria, DPGN and female sex.