Early PLA2R Status in Severe Anti-PLA2R-mediated Membranous Nephropathy and Long Term Kidney Outcome. (EPSILON)
This is a multicentric retrospective observational cohort study. The aim of this study is to evaluate, during the initial phase of immunosuppressive treatment for severe PLA2R-positive membranous nephropathy, the independent association between anti-PLA2R antibody trajectories and the occurrence of long-term major kidney events (within 10 years after treatment initiation).
The secondary objectives are :
To assess the association between the initial anti-PLA2R antibody trajectory (between 0 and 6 ± 3 months after treatment, before any potential re-treatment) and the occurrence of nephrological remission.
To assess the association between the initial anti-PLA2R antibody trajectory (between 0 and 6 ± 3 months after treatment, before any potential re-treatment) and the occurrence of immunological remission.
To evaluate, in real-world practice, the safety of immunosuppressive therapies in the treatment of severe PLA2R-positive membranous nephropathy.
Visão geral do estudo
Status
Descrição detalhada
Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in non-diabetic Caucasian adults, with a highly variable disease course. One-third of patients achieve spontaneous remission, one-third develop chronic kidney disease, and another third progress to end-stage renal disease (ESRD). This variability necessitates early risk assessment to prevent both overtreatment and disease progression.
Anti-PLA2R antibodies, detected in 60-65% of cases, are crucial for diagnosis and disease monitoring. High antibody levels are associated with a low likelihood of spontaneous remission, often justifying early immunosuppressive therapy. However, the precise predictive value and threshold levels of these antibodies remain unclear.
Among available immunosuppressive treatments, rituximab is favored for its efficacy and low toxicity, making it the standard therapy for MN. However, only 30-35% of patients achieve complete remission within two years, while two-thirds of those without complete remission remain at risk of progression to ESRD.
This variability in response to rituximab is likely influenced by several factors, including excessive urinary drug loss, immune resistance, genetic predispositions, and comorbidities such as obesity and vitamin D deficiency. Although personalized therapeutic approaches are under investigation, large-scale validation is needed.
In conclusion, despite significant advancements, particularly with anti-PLA2R antibodies and rituximab, multicenter studies are required to refine therapeutic strategies and improve long-term outcomes in anti-PLA2R+ MN by promoting a more personalized approach to treatment.
Tipo de estudo
Inscrição (Estimado)
Contactos e Locais
Contato de estudo
- Nome: Romain BROUSSE, MD, PhD student
- Número de telefone: +33156017043
- E-mail: Romain.brousse@aphp.fr
Estude backup de contato
- Nome: Karine DAHAN, MD
- E-mail: Karine.dahan@aphp.fr
Locais de estudo
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Paris, França, 75020
- Néphrologie & Dialyses department, Tenon Hospital
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Contato:
- Romain BROUSSE, MD, PhD student
- Número de telefone: +33156017043
- E-mail: Romain.brousse@aphp.fr
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Contato:
- Karine DAHAN, MD
- E-mail: Karine.dahan@aphp.fr
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Método de amostragem
População do estudo
Patients with antiPLA2R positive membranous nephropathy will be obtained from the immunology laboratories of Saint Antoine Hospital and Mondor Hospital (performing all antiPLA2R analysis in Paris).
Descrição
Inclusion Criteria:
- Patient followed in 8 nephrology departments of AP-HP between 01/01/2017 and 12/31/2026
- Age > 6 years
- With serodiagnosis of MN via identification of anti-PLA2R antibodies
- Treatment with an immunosuppressive drug.
Exclusion Criteria:
- Diagnosis of MN without testing for anti-PLA2R antibodies
- Refusal to use the data
- Occurrence of the primary endpoint at the time of disease diagnosis (diagnosis of membranous nephropathy at the stage of end-stage kidney disease)
- Lack of patient follow-up at the centers participating in the study
- Lack of reassessment of anti-PLA2R antibody titers within 12 months after initiation of immunosuppressive therapy
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Modelos de observação: COHORT
- Perspectivas de Tempo: RETROSPECTIVE
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Occurrence of a major nephrological event within 10 years following immunosuppressive treatment for anti-PLA2R-positive membranous nephropathy
Prazo: between diagnostic and last follow-up, up to 10 years
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Major adverse kidney event (MAKE) - Composite variable defined by one of the following event:
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between diagnostic and last follow-up, up to 10 years
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Association between the initial trajectory (defined as the percentage change ((M6 - M0)/M0) in the anti-PLA2R antibody titer
Prazo: between diagnostic and last follow-up, , up to 10 years
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Association between the initial trajectory (defined as the percentage change ((M6 - M0)/M0) in the anti-PLA2R antibody titer, quantified using the ELISA technique, between the titer at the time of initiation of immunosuppressive therapy (D0) and the titer from the first anti-PLA2R measurement performed at 6 ± 3 months after initiation of immunosuppressive therapy (M6 ± 3)) of anti-PLA2R antibodies (from 0 to 6+/-3 months post-treatment) and the occurrence of nephrological response (either complete and/or partial). Nephrological relapse is defined as :
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between diagnostic and last follow-up, , up to 10 years
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Association between the initial trajectory of anti-PLA2R antibodies (from 0 to 6 +/- 3 months post-treatment) and the occurrence of immune response
Prazo: between diagnostic and last follow-up, , up to 10 years
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Immunological relapse is defined as reappearance of detectable anti-PLA2R antibodies by ELISA after achieving anti-PLA2R antibody negativity during treatment. |
between diagnostic and last follow-up, , up to 10 years
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Safety of immunosuppressive drugs
Prazo: between diagnostic and last follow-up, , up to 10 years
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Reporting of all adverse event recorded in patients' medical record during follow up. Scoring performed according to the CTCAE v5.0. |
between diagnostic and last follow-up, , up to 10 years
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Romain BROUSSE, MD, PhD student, Assistance Publique - Hôpitaux de Paris
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- APHP251555
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