# Fibrillary glomerulonephritis disease natural history and outcomes: a retrospective two centre cohort study

## TL;DR

This study examines the progression and outcomes of a rare kidney disease called fibrillary glomerulonephritis (FGN) in a UK-based patient cohort.

## Contribution

The study provides a detailed natural history of FGN in a UK cohort and explores the potential role of immunosuppressive therapy.

## Key findings

- 33% of patients progressed to end-stage kidney disease within 12 months of diagnosis.
- DNAJB9 staining was positive in all tested cases, supporting its use as a diagnostic biomarker.
- Immunosuppressive therapy was associated with slower eGFR decline in some patients.

## Abstract

Fibrillary glomerulonephritis (FGN) is a rare immune complex-mediated glomerulonephritis characterised by the deposition of anomalous fibrillary structures within the glomeruli.

The prognosis for patients with FGN is usually poor with rapid progression to end stage kidney disease (ESKD). There are currently limited data to suggest an optimal therapy strategy to prevent this. Most case series describing FGN come from North America with limited research from the UK.

This is a retrospective case series of patients who presented with biopsy proven FGN to two renal centres within the West Midlands, between 2006 and 2022.

Twenty-one patients with a histological diagnosis of FGN were identified within the 16-year period. Median eGFR at the time of biopsy was 29 mL/min/1.7 (IQR 18–55), serum albumin 31 g/L (IQR 28–33) and ACR was 368 mg/mmol (IQR 303–596). The median follow-up for the cohort was 50 months (range 12–138). DNAJB9 staining was done for five patients, all were positive.

Immunosuppression was used in 8 patients following diagnosis of FGN. Treatment varied between steroid, rituximab and cyclophosphamide. Patients with crescents on the biopsy were more likely to receive a trial of immunosuppression. Progression to ESKD was common, 7 (33%) patients required renal replacement therapy within 12 months of diagnosis of FGN.

To date, there are limited numbers of case series of FGN due to the rare nature of the disease. We describe the natural history of this rare kidney condition, and highlight the challenges faced by clinicians where evidence for successful therapeutic options is lacking.

- Fibrillary glomerulonephritis (FGN) is a rare immune complex-mediated glomerulonephritis first described in 1977 by Rosenmann and Eliakim, in those with unique histological findings of fibrillary structures on renal biopsy.

- Staining for DNA heat shock protein family (Hsp40) member B9 (DNAJB9) has 98–100% sensitivity and > 99–100% specificity as a biomarker for the diagnosis of FGN. It is not found in healthy glomeruli or other comparable glomerular diseases.

- There are currently limited data to suggest an optimal therapeutic strategy to prevent renal function decline with trials of steroids along with immunomodulation treatments demonstrating inconclusive results.

- We describe the natural history of fibrillary glomerulonephritis and highlight the challenges faced by clinicians where evidence for successful therapeutic options is lacking.

- In our case series, 38% of patients received immunosuppressive therapy with some demonstrating a slower decline in eGFR over time following treatment.

- This case series further highlights the poor overall prognosis of this condition with a significant number (33%) of patient requiring renal replacement therapy within 12 months of diagnosis and an average eGFR decline of 1 ml/min.

- All of the histology samples from our case series which were tested for DNAJB9 yielded a positive result. Future research on serum and urine levels of DNAJB9 may provide a non-invasive way of diagnosing FGN.

- There is very limited evidence that immunosuppressive therapy is effective in slowing the progression of FGN, our study highlights the potential benefit of this treatment in selected patients, and this warrants further evaluation.

- The study highlights the grim prognosis of FGN with rapid progression to ESKD, we urge for larger scale studies with global or national registry data to obtain more powerful results.

Not applicable.