Therapeutic Challenges and New Era in Fibrillary Glomerulonephritis with the Introduction of DNAJB9: Experience from a Tertiary Nephrology Center

Background/Aim: Fibrillary glomerulonephritis (FGN) is a rare glomerular disease characterized by non-amyloid fibrillary deposits in the glomeruli and positive staining for DNAJB9. There is currently no treatment of choice, and the poor prognosis highlights the need for further research. We aimed to investigate the clinical and pathological characteristics and outcomes of FGN patients from a tertiary nephrology center. Methods: A retrospective cohort study of eleven patients diagnosed with FGN between 2016 and 2025, based on kidney biopsy and DNAJB9 positivity, was used. Partial response was defined as a ≥50% reduction in proteinuria with stable renal function. Results: At diagnosis, nine patients had nephrotic-range proteinuria, and eight had microscopic hematuria. Mean serum creatinine was 1.6 mg/dL, and mean proteinuria was 3.78 g/24 h. Comorbidities included SLE (n = 1), sarcoidosis (n = 1), and lung cancer (n = 1). The most common histological pattern was mesangial proliferative (n = 6). DNAJB9 staining was positive in five patients. All patients received RAAS blockade and immunosuppression (e.g., corticosteroids, rituximab). Partial response occurred in 73% with a median follow-up of 24 months, with 80% showing >50% proteinuria reduction. One patient died during follow-up; no patients progressed to ESRD or required dialysis. Conclusions: FGN is clinically diverse and lacks a standard treatment. The small sample size limits generalizability.