The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult

Tedesco, Martina; Mescia, Federica; Pisani, Isabella; Allinovi, Marco; Casazza, Giovanni; Vecchio, Lucia Del; Santostefano, Marisa; Cirillo, Luigi; Ferrario, F; Esposito, Ciro; Esposito, Pasquale; Santoro, Domenico; Lazzarin, Roberta; Rossi, Giovanni Maria; Fiaccadori, Enrico; Ferrantelli, Angelo; Sinico, Renato Alberto; Cozzolino, Mario; Gallieni, Maurizio; Cirami, Lino; Scolari, Francesco; Vaglio, Augusto; Alberici, Federico; Affatato, Stefania; Caroti, Leonardo; Mancini, Elena; Semeraro, Luca; Siligato, Rossella; Cassia, Matthias; Napodano, Pietro; Calatroni, Marta; Distratis, Cosimo; Campo, Andrea

doi:10.1016/j.ekir.2022.05.024

Cited by 13 publications

(18 citation statements)

References 36 publications

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“…Rituximab (RTX) is a human-mouse chimeric monoclonal antibody, which can specifically bind to CD20 molecules on the surface of B cells [5] , eliminate B cells through antibody or complement-mediated cytotoxicity, apoptosis induction and other ways, and is safe and effective for the treatment of a variety of immune diseases. The results of some observational studies and controlled clinical trials have shown good efficacy of RTX in the treatment of minimal change nephropathy [6,7] and nephrotic syndrome caused by primary membranous nephropathy [8,9] .There are few clinical studies on the treatment of FSGS patients with RTX in China and abroad [10] , and most of them have limitations such as small sample size and inconsistent treatment plans [11][12][13][14][15][16][17][18][19] . We retrospectively analyzed the clinical data of patients with primary FSGS treated with RTX to evaluate the efficacy and safety of RTX in the treatment of FSGS.…”

Section: Introductionmentioning

confidence: 99%

Rituximab treatment of adults with primary focal segmental glomerulosclerosis

wang

et al. 2023

Preprint

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Objective: To evaluate the efficacy and safety of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) in adults. Method: The clinical data of patients with primary FSGS who received RTX treatment in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively. The selected patients received RTX twice or four times, with a single dose of 375mg/m2, and the interval between two times of administration of RTX was 2-4 weeks. The treatment target is to achieve the clearance of B cells (peripheral blood B cell count<5/ μ l). The primary outcome measures were remission and recurrence of renal disease, and the secondary outcome measures were adverse events (AEs) and renal outcomes. Result: A total of 14 FSGS patients were included, including 12 males, 9 with glucocorticoid-dependent or frequently relapsing nephrotic syndrome, and 3 with newly diagnosed nephrotic syndrome. After RTX treatment, 7 patients with glucocorticoid-dependent/recurrent nephrotic syndrome were completely relieved. At 6 months of follow-up, glucocorticoids were discontinued in all patients except 1 patient. The other 5 patients achieved partial remission (PR), of which 1 patient relapsed after PR, and 1 initial patient achieved complete remission (CR). One patient progressed to end-stage renal disease (ESRD) after 4 months of follow-up. Conclusion: RTX in the treatment of adult glucocorticoid-dependent/relapsing FSGS can reduce the risk of recurrence and help to decline or discontinue the use of glucocorticoid and immunosuppressants. Keywords: Rituximab, FSGS, treatment effect, SDNS, FRNS

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Section: Introductionmentioning

confidence: 99%

Rituximab treatment of adults with primary focal segmental glomerulosclerosis

wang

et al. 2023

Preprint

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“…Rituximab (RTX) is a human-mouse chimeric monoclonal antibody, which can specifically bind to CD20 molecules on the surface of B cells 5 , eliminate B cells through antibody or complement-mediated cytotoxicity, apoptosis induction and other ways, and is safe and effective for the treatment of a variety of immune diseases. The results of some observational studies and controlled clinical trials have shown good efficacy of RTX in the treatment of minimal change nephropathy 6 , 7 and nephrotic syndrome caused by primary membranous nephropathy 8 , 9 .There are few clinical studies on the treatment of FSGS patients with RTX in China and abroad 10 , and most of them have limitations such as small sample size and inconsistent treatment plans 11 – 19 . We retrospectively analyzed the clinical data of patients with primary FSGS treated with RTX to evaluate the efficacy and safety of RTX in the treatment of FSGS.…”

Section: Introductionmentioning

confidence: 99%

Rituximab treatment of adults with primary focal segmental glomerulosclerosis

Wang

et al. 2023

Sci Rep

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To evaluate the efficacy and safety of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) in adults. The clinical data of patients with primary FSGS who received RTX treatment in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively. The selected patients received RTX twice or four times, with a single dose of 375 mg/m2, and the interval between two times of administration of RTX was 2–4 weeks. The treatment target is to achieve the clearance of B cells (peripheral blood B cell count < 5/μl). The primary outcome measures were remission and recurrence of renal disease, and the secondary outcome measures were adverse events and renal outcomes. A total of 14 FSGS patients were included, including 12 males, 9 with glucocorticoid-dependent or frequently relapsing nephrotic syndrome, and 3 with newly diagnosed nephrotic syndrome. After RTX treatment, 7 patients with glucocorticoid-dependent/recurrent nephrotic syndrome were completely relieved. At 6 months of follow-up, glucocorticoids were discontinued in all patients except 1 patient. The other 5 patients achieved partial remission (PR), of which 1 patient relapsed after PR, and 1 initial patient achieved complete remission. One patient progressed to end-stage renal disease (ESRD) after 4 months of follow-up. RTX in the treatment of adult glucocorticoid-dependent/relapsing FSGS can reduce the risk of recurrence and help to decline or discontinue the use of glucocorticoid and immunosuppressants.

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“…B cell neoplasms, as well as responsiveness to immunomodulatory therapies, including corticosteroid therapy and B cell depletion (21,22). With regard to inherited factors, genome-wide association studies (GWAS) have shown that steroid-sensitive nephrotic syndrome, including MCD and primary FSGS, is associated with genomic susceptibility loci in HLA regions (23)(24)(25) and non-HLA regions (23,26), most of which are linked to the immune system.…”

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The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis

et al. 2023

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Primary focal segmental glomerulosclerosis (FSGS), typically characterized by diffuse podocyte foot process effacement and nephrotic syndrome (diffuse podocytopathy), is generally attributed to a circulating permeability factor. Primary FSGS can recur after transplantation where it manifests as diffuse foot process effacement in the early stages, with subsequent evolution of segmental sclerotic lesions. Previous published literature has been limited by the lack of stringent selection criteria to define primary FSGS. Although immunogenetic factors play an important role in many glomerular diseases, their role in recurrent primary FSGS post-transplantation has not been systematically investigated. To address this, we retrospectively studied a multicenter cohort of 74 kidney allograft recipients with end stage kidney disease due to primary FSGS, confirmed by clinical and histologic parameters. After adjusting for race/ethnicity, there was a numeric higher frequency of HLA-A30 antigen in primary FSGS (19%) compared to each of 22,490 healthy controls (7%, adjusted OR=2.0, P=0.04) and 296 deceased kidney donors (10%, OR=2.1, P=0.03). Within the group of transplant patients with end stage kidney disease due to primary FSGS, donor HLA-A30 was associated with recurrent disease (OR=9.1, P=0.02). Multivariable time-to-event analyses revealed that recipients who self-identified as Black people had lower risk of recurrent disease, probably reflecting enrichment of these recipients with APOL1 high-risk genotypes. These findings suggest a role for recipient and donor immunogenetic makeup in recurrent primary FSGS post-transplantation. Further larger studies in well-defined cohorts of primary FSGS that include high-resolution HLA typing and genome-wide association are necessary to refine these hereditary signals.

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The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult

Cited by 13 publications

References 36 publications

Rituximab treatment of adults with primary focal segmental glomerulosclerosis

Rituximab treatment of adults with primary focal segmental glomerulosclerosis

Rituximab treatment of adults with primary focal segmental glomerulosclerosis

The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis

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