Comorbidities, Biopsy Characteristics, and Kidney Outcomes in a Cohort of Patients with DNAJB9-Positive Fibrillary Glomerulonephritis

Background: Fibrillary glomerulonephritis (FGN) is a rare glomerular disease historically associated with poor renal prognosis and the recent identification of DNAJ homolog subfamily B member 9 (DNAJB9) as a highly specific immunohistochemistry (IHC) marker has significantly enhanced diagnostic precision. Due to its rarity, data on long-term renal survival remain limited. Methods: Retrospective cohort study conducted on patients with biopsy proven DNAJB9-positive fibrillary glomerulonephritis from January 2013 to august 2024. Laboratory values, including proteinuria and estimated glomerular filtration rate (eGFR),were obtained at the time of kidney biopsy.Time to event analysis with the outcomes end stage kidney disease (ESKD) and death was performed. Results: 84 patients included, 65.5% female, 96.4% white.Median age of 58.7 [51.7, 65.6] years. Baseline median serum creatinine was 1.56 [1.1, 2.28] mg/dL; eGFR was 43.5 [26.2, 78.9] mL/min/1.73m2; proteinuria was 2.8 [1.1, 6.2] g/24h; and serum albumin was 3.6 [3.12, 4.10] g/dL. The most frequent comorbidity after hypertension was glucose metabolism impairment in 37 patients (44%), 27 (32.1%) with diabetes mellitus (DM) and 10 (11.9%) with prediabetes (pre-DM). 47.6% received immunosuppressive therapy (IS), 18 (27.7%) received Rituximab (RTX), 11 (13.1%) RTX associated with other IS, 4(4.7%) received cyclophosphamide, 3(3.6%) MMF, 3(3.6%) cyclosporine plus ACTH. 38.8% achieved proteinuria remission, 19 of whom received IS.At diagnosis, 4.7% were on dialysis, and 28.75% progressed to ESKD over a median follow-up of 27.9 months. Renal survival estimates were 86.4% at one year and 63% at five years. Higher ESKD risk was linked to eGFR<30 mL/min/1.73m2[HR 9.97(95% CI 3.75-26.5)] higher interstitial fibrosis/ tubular atrophy (IFTA)[HR (per 1%) 1.05 (95% CI 1.02-1.07)], and glomerulosclerosis[HR (per 1%) 1.01 (95% CI 1.0-1.03)]. 7.14% of patients died, with a five-year survival of 91.1%.Higher death risk was associated with DM(HR 9.3(95% CI 1.08-79.83)), low hemoglobin(HR(per 1g/dl)0.62,(95% CI 0.39- 0.98),and high IFTA[HR (per 1%) 1.03(95% CI 1.00-1.06)] Conclusion: Compared to historically poor prognoses, our DNAJB9 FGN cohort demonstrated improved renal survival, suggesting better outcomes than previously reported.