Víctor J. Escudero-Saiz , Ángela Gonzalez , Adriana García-Herrera , Ana B. Larque , Andrew S. Bomback , Laura Morantes , Marta Martínez-Chillarón , Júlia Ollé , Elena Guillén , Marc Xipell , Alicia Molina-Andújar , Diana Rodríguez , Elena Cuadrado , Judit Cacho , Carolt Arana , Núria Esforzado , Carla Bastida , Esteban Poch , Fritz Diekman , David Cucchiari , Miquel Blasco
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Fortunately, new molecules are being developed that specifically target the proximal alternative complement pathway, such as iptacopan, a factor B inhibitor that showed promising results in native kidneys and cases of transplant recurrence in a phase 2 clinical trial. We present 2 “real-world” cases of C3 glomerulopathy recurrence in kidney allografts treated with iptacopan, with initial excellent clinical response and safety profile, especially with early introduction. We also present follow-up biopsies that showed no C3 deposition during factor B inhibition. 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引用次数: 0
摘要
C3 肾小球病是一种罕见的疾病,由替代性补体途径的液相失调引起。目前,治疗方法取决于临床和组织学的严重程度,包括肾保护、非特异性免疫抑制和末端补体阻断剂(C5),但尚未批准病因治疗方法。C3 肾小球病在肾移植后的复发率很高,移植物丢失的风险也很高。幸运的是,目前正在开发专门针对近端替代补体途径的新分子,例如 B 因子抑制剂 iptacopan,在一项二期临床试验中,它在原生肾脏和移植复发病例中显示出良好的效果。我们介绍了两例接受伊帕考潘治疗的异体肾脏C3肾小球病复发的 "真实世界 "病例,这些病例最初的临床反应和安全性都非常好,尤其是在早期使用的情况下。我们还介绍了随访活检结果,结果显示因子 B 抑制期间没有 C3 沉积。我们的病例表明,近端阻断替代补体途径可有效、安全地治疗肾移植中的C3肾小球病复发,这也带来了其他问题,如双重阻断(如C3和C5)、从因子B抑制中获益的最佳患者情况或治疗持续时间,以及在其他形式的膜增生性肾小球肾炎(如免疫复合物介导的肾小球肾炎)中的潜在应用。
Factor B Inhibition with Iptacopan in Recurrent C3 Glomerulopathy Following Kidney Transplant: A Report of Two Cases
C3 glomerulopathy is a rare disease caused by fluid phase dysregulation of the alternative complement pathway. Currently, treatment depends on clinical and histological severity and includes nephroprotection, unspecific immunosuppression, and terminal complement blockers (C5), without having an etiological treatment approved. C3 glomerulopathy has high recurrence rates after kidney transplantation with a high risk of graft loss. Fortunately, new molecules are being developed that specifically target the proximal alternative complement pathway, such as iptacopan, a factor B inhibitor that showed promising results in native kidneys and cases of transplant recurrence in a phase 2 clinical trial. We present 2 “real-world” cases of C3 glomerulopathy recurrence in kidney allografts treated with iptacopan, with initial excellent clinical response and safety profile, especially with early introduction. We also present follow-up biopsies that showed no C3 deposition during factor B inhibition. Our cases suggest that proximal blockade of the alternative complement pathway can be effective and safe in the treatment of C3 glomerulopathy recurrence in kidney transplantation, bringing other questions such as dual blockade (eg, in C3 and C5), the optimal patient profile to benefit from factor B inhibition or treatment duration and its potential use in other forms of membranoproliferative glomerulonephritis (eg, immune complex-mediated).