University Grenoble Alpes - CHU Grenoble Alpes - Service de Néphrologie, Dialyse, Aphérèses et Transplantation, Grenoble, France.
Curr Opin Organ Transplant. 2022 Oct 1;27(5):415-420. doi: 10.1097/MOT.0000000000001016. Epub 2022 Aug 3.
Antibody-mediated rejection (AMR) is the leading cause of kidney graft loss. Very few treatment options are available to the clinician to counter this disease process. In this review we describe the available therapeutics and the novel approaches that are being currently developed.
AMR treatment requires a multidrug approach. Imlifidase, a new immunoglobulin G cleaving agent, may prove to be the perfect replacement of apheresis. New complement blockers other than eculizumab are in development in order to block acute kidney damage in the delicate phase following antibody removal. Plasma cell depletion is being explored in chronic AMR: studies are in progress with daratumumab and felzartamab. Interleukin 6 inhibition is generating enthusiasm in the chronic setting with preliminary encouraging results.
In acute AMR, the clinicians will have to remove the antibodies, avoid rebound and block specific damage effectors. In chronic AMR they will need to reduce the inflammatory response induced by donor specific antibodies. New drugs are available and transplant physicians are starting to develop effective multidrug strategies to counter the complex disease mechanisms. Safety of these drugs needs to be further explored especially when used together with other potent immunosuppressive drugs.
抗体介导的排斥反应(AMR)是导致肾移植失败的主要原因。临床医生可用的治疗选择非常有限,无法应对这种疾病进程。在本次综述中,我们描述了现有的治疗药物和当前正在开发的新方法。
AMR 的治疗需要多药物联合方案。一种新型免疫球蛋白 G 切割剂 imlifidase 可能是血浆去除术的理想替代品。为了阻止抗体清除后微妙阶段的急性肾损伤,正在开发除依库珠单抗以外的新型补体阻滞剂。在慢性 AMR 中正在探索浆细胞耗竭:正在进行达雷木单抗和 felzartamab 的研究。白细胞介素 6 抑制在慢性环境中引起了关注,初步结果令人鼓舞。
在急性 AMR 中,临床医生将不得不清除抗体、避免反弹并阻断特定的损伤效应因子。在慢性 AMR 中,他们需要减轻供体特异性抗体诱导的炎症反应。新的药物已经问世,移植医生开始制定有效的多药物策略来对抗复杂的疾病机制。这些药物的安全性需要进一步研究,特别是当与其他强效免疫抑制剂联合使用时。