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.
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Romain BROUSSE, MD, PhD student
- 電話番号：+33156017043
- メール：Romain.brousse@aphp.fr
研究連絡先のバックアップ
- 名前：Karine DAHAN, MD
- メール：Karine.dahan@aphp.fr
研究場所
-
-
-
Paris、フランス、75020
- Néphrologie & Dialyses department, Tenon Hospital
-
コンタクト：
- Romain BROUSSE, MD, PhD student
- 電話番号：+33156017043
- メール：Romain.brousse@aphp.fr
-
コンタクト：
- Karine DAHAN, MD
- メール：Karine.dahan@aphp.fr
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
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).
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：COHORT
- 時間の展望：RETROSPECTIVE
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Occurrence of a major nephrological event within 10 years following immunosuppressive treatment for anti-PLA2R-positive membranous nephropathy
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Association between the initial trajectory (defined as the percentage change ((M6 - M0)/M0) in the anti-PLA2R antibody titer
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
捜査官
- 主任研究者：Romain BROUSSE, MD, PhD student、Assistance Publique - Hôpitaux de Paris
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- APHP251555
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。