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.
Přehled studie
Postavení
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Kontakty a umístění
Studijní kontakt
- Jméno: Romain BROUSSE, MD, PhD student
- Telefonní číslo: +33156017043
- E-mail: Romain.brousse@aphp.fr
Studijní záloha kontaktů
- Jméno: Karine DAHAN, MD
- E-mail: Karine.dahan@aphp.fr
Studijní místa
-
-
-
Paris, Francie, 75020
- Néphrologie & Dialyses department, Tenon Hospital
-
Kontakt:
- Romain BROUSSE, MD, PhD student
- Telefonní číslo: +33156017043
- E-mail: Romain.brousse@aphp.fr
-
Kontakt:
- Karine DAHAN, MD
- E-mail: Karine.dahan@aphp.fr
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Metoda odběru vzorků
Studijní populace
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).
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Observační modely: COHORT
- Časové perspektivy: RETROSPECTIVE
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Occurrence of a major nephrological event within 10 years following immunosuppressive treatment for anti-PLA2R-positive membranous nephropathy
Časové okno: between diagnostic and last follow-up, up to 10 years
|
Major adverse kidney event (MAKE) - Composite variable defined by one of the following event:
|
between diagnostic and last follow-up, up to 10 years
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Association between the initial trajectory (defined as the percentage change ((M6 - M0)/M0) in the anti-PLA2R antibody titer
Časové okno: between diagnostic and last follow-up, , up to 10 years
|
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 :
|
between diagnostic and last follow-up, , up to 10 years
|
|
Association between the initial trajectory of anti-PLA2R antibodies (from 0 to 6 +/- 3 months post-treatment) and the occurrence of immune response
Časové okno: between diagnostic and last follow-up, , up to 10 years
|
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
|
|
Safety of immunosuppressive drugs
Časové okno: between diagnostic and last follow-up, , up to 10 years
|
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
|
Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Romain BROUSSE, MD, PhD student, Assistance Publique - Hôpitaux de Paris
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
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