FIBRILLARY GLOMERULONEPHRITIS: ANALYSIS OF CASES DIAGNOSED OVER 14 YEARS

Fibrillary glomerulonephritis (FGN) is a rare disease observed in 0.5-1% of native kidney biopsies.To analyse cases of FGN from June 2011 to June 2024 in our centre. 

Data of patients (pts) older than 18 years of age with a histological diagnosis of FGN (deposition of IgG, usually IgG4, and C3 in mesangium and/or capillary walls of glomerulus; Congo red negative) through both light and electron microscopy and immunohistochemistry techniques (DNAJB9) was analysed. Baseline demographics, clinical variables, laboratory findings, treatment performed, and follow-up of included pts were recorded.

Out of 250 consecutive native kidney biopsies, five patients were diagnosed with FGN, yielding a frequency of 2% and incidence of 0.35 cases/year. Mean age at diagnosis was 61.6±11.84 years (range 47-79) and 60% were women (ratio 1.5:1). Mean age for women and men was 54.3±6.3 years and 72.5±9.2 years, respectively (p=0.16). Four pts were hypertensive, and one of these was diabetic. Haematuria and proteinuria were present in all pts at baseline; one of them had nephrotic syndrome, and two had nephrotic proteinuria. Two pts showed antinuclear antibodies positive. Other autoimmunity tests, hypocomplementemia, paraprotein in blood and urine, and hepatitis C virus serologies were negative. One patient had a history of relapsing remitting multiple sclerosis and developed parathyroid carcinoma more than five years later. Another patient had a history of prostate cancer. Overall, mean serum creatinine (Cr) and glomerular filtration rate (eGFR) were 1.4±0.8 mg/dl and 59.1±28.2 ml/min/1.73m², respectively. Three pts had kidney failure (KF) at diagnosis showing an eGFR 52, 54 and 18.3 ml/min/1.73m². Mean age of KF pts, 61.33±16.25 years, did not differ significantly from non-KF pts, 62±5.6 years, p=0.95. The light microscopy patterns were the following: two diffuse sclerosis, one membranoproliferative, one mesangial and one associated with membranous glomerulonephritis. Two pts were diagnosed by electron microscopy and three by positivity for DNAJB9. All pts were treated with renin angiotensin aldosterone system blockers, three pts were also treated with sodium-glucose cotransporter type 2 inhibitors and two pts with diffuse sclerosis pattern and KF received Rituximab for worsening proteinuria and kidney function. Mean follow-up was 63.86±66.11 months (range 8.08-159.8). The pts with diffuse sclerosis were women and progressed to end-stage kidney disease (ESKD) after 15±1.2 months of follow-up. One of them were treated through haemodialysis and, 38 months later, received a kidney graft (KG) with a good function to date (Cr 1.13 mg/dl, eGFR 53 ml/min/1.73m²) without haematuria and 0.3 g/day of proteinuria. The second woman was on peritoneal dialysis during 13 months, when she received a first KG, which functioned during 51 months until its failure for unclear reasons (no evidence of FGN recurrence or rejection); subsequently she received a second KG functioning during 24 months until now (Cr 1.18 mg/dl, eGFR 48 ml/min/1.73m², without haematuria and 0.2 g/day of proteinuria). The other three pts had improvement in eGFR and proteinuria values showing two complete remission and one partial remission. Differences in the variables age, proteinuria and blood albumin were assessed between pts who progressed to Kidney Replacement Therapy (RRT) and those who did not. Pts who progressed to RRT had a lower age compared to those who did not progress (median age was 52.5 years vs 67.7 years, p = 0.236). Proteinuria was higher in RRT group (mean = 7.5 g/day) compared to no-RRT group (mean = 3.26 g/day), p = 0.800. RRT pts had lower albumin levels (mean = 3.3 g/dL) versus the no-RRT group (mean = 4.03 g/dL), p = 0.200. Figure 1. None of the pts died during follow-up. 

1) FGN was diagnosed more frequently than expected. 2) Forty percent of pts reached ESKD in less than 2 years, despite treatment with rituximab. 3) The ESKD development was exclusive for women. 4)The systematic use of DNAJB9 immunohistochemistry may improve the diagnosis of FGN at earlier stages, allowing for timely therapeutic interventions and potentially better long-term outcomes.