Clinicopathologic features and outcomes of patients with DNAJB9 positive fibrillary glomerulonephritis

Abstract Background Fibrillary glomerulonephritis (FGN) is a very rare glomerular disease characterized by non-branching fibril deposition and DNAJB9 positivity. We aimed to analyze our cohort to better elucidate clinicopathologic features and outcomes of patients with FGN. Methods Adult patients diagnosed with FGN between 2007-2025 and showing DNAJB9 positivity were included. Primary composite outcome was defined as doubling of serum creatinine from baseline, undergoing dialysis or transplantation, development of stage 5 CKD or death. Results Fifty native kidney biopsies of 44 patients were examined, 17 belonged to males (34%). Most common patterns of injury were mesangial (24, 48%) and membranoproliferative (16, 32%). Mean fibril diameter was 13.7±2.5 nm. Eight biopsies (16%) showed atypical variants such as congophilia, light chain restriction on frozen immunoflorescence and IgG negativity. Out of 44 patients, 25 (56.8%) had adequate follow-up data, mean age was 48.4±12.7 years. Over a median of 27 (7.5-89.5) months, 13 patients (52%) reached primary composite outcome, 10 (40%) underwent kidney replacement therapies and 3 (12%) died. Multivariate logistic regression models showed hemoglobin predicted the primary outcome whereas histopathological features or immunosuppressive use did not. Baseline serum C3 was associated with primary outcome (AUC: 0.759, 0.525-0.916) with 134 mg/dl as cut-off value. Kidney survival rate was 30.8% in patients with serum C3 ≤134 mg/dl and 87.5% in serum C3 >134 mg/dl. However, multivariate regression models failed to show a clear association between serum C3 levels and primary outcome. Conclusions Atypical histopathological features are not uncommon in FGN, complicating the differential diagnosis. Prognosis is still quite dismal despite immunosuppressive use. Lower baseline hemoglobin might indicate poorer outcomes.