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Abstract: TH-PO0769

Fibrillary Glomerulonephritis: Long-Term Effects of Two Anti-CD20 Regimens and Lesson from Repeat Biopsy

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Roccatello, Dario, Nephrology and Dialysis Unit, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
  • Fenoglio, Roberta, Nephrology and Dialysis Unit, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
Background

Fibrillary glomerulonephritis (GNF) is characterized by a severe renal prognosis. DnaJ homolog subfamily B member 9 (DNAJB9) has been identified as a specific tissue marker for FGN. It has been suggested that IgG may bind to pre-existing fibrils and DNAJB9 may act as an autoantigen. Data on the optimal therapeutic strategy are limited. Different drugs were administered. This paper aims to evaluate the clinical and histological effects of two rituximab-based regimens in fibrillary glomerulonephritis.

Methods

Twenty-one patients with diagnosis of GNF managed in a single Center (1996-2023), were identified. Seventeen patients, since 2010, were treated with anti-CD20 antibodies and included in the present study. Eleven patients were treated with Rituximab monotherapy (Group 1), 6 with the Intensified B-cell depletion therapy protocol (IBCDT) (Group 2) which consists of the combination of low-dose rituximab, IV cyclophosphamide and steroids.

Results

Five women and 12 men with a median age of 54 years were evaluated. At baseline mean serum creatinine and proteinuria were 2.0 mg/dL and 3.7 g/day respectively. In group 1, four patients (36.4%) achieved an overall response (2 complete and 2 partial) and 7 patients failed to respond. In group 2 (IBCDT group), five out of 6 patients (83.3%) had an overall response (p=0.0064). All patients with an overall response had a percentage of sclerotic glomeruli ≤ 40%. Median follow-up was 41 months (range 6-276). During follow-up 8 out of 17 patients underwent a repeat biopsy. Patients who underwent a 2nd renal biopsy had an increase in glomerular sclerosis even in the presence of a complete response (p=0.021).

Conclusion

Renal prognosis in FGN is poor. Presently, no standard-of-care treatment is available. Rituximab seemed to achieve encouraging results in progressive FGN without severe renal impairment at diagnosis and remained the single promising therapeutic agent. Our study allowed comparisons of outcome of patients treated with different regimens of B cell depletion. The overall response to rituximab was 53%, but when examining results shown by patients receiving anti-CD20 alone and those receiving the IBCD protocol, a significantly better overall and complete response was achieved using the more B-cell depleting IBCD regimen.

Digital Object Identifier (DOI)