PDF(Pubmed)
Abstract：
Chronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other complications. Kidney transplantation is a renal-replacement therapy that offers better survival compared to dialysis. Antibody-mediated rejection (ABMR) is a significant complication following kidney transplantation: it contributes to both short- and long-term injury. The standard-of-care (SOC) therapy combines plasmapheresis and Intravenous Immunoglobulins (IVIg) with or without steroids, with or without rituximab: however, despite this combined treatment, ABMR remains the main cause of graft loss. IL-6 is a key cytokine: it regulates inflammation, and the development, maturation, and activation of T cells, B cells, and plasma cells. Tocilizumab (TCZ) is the main humanized monoclonal aimed at IL-6R and appears to be a safe and possible strategy to manage ABMR in sensitized recipients. We conducted a literature review to assess the place of the anti-IL-6R monoclonal antibody TCZ within ABMR protocols.
We systematically reviewed the PubMed literature and reviewed six studies that included 117 patients and collected data on the utilization of TCZ to treat ABMR.
Most studies report a significant reduction in levels of Donor Specific Antibodies (DSAs) and reduced inflammation and microvascular lesions (as found in biopsies). Stabilization of the renal function was observed. Adverse events were light to moderate, and mortality was not linked with TCZ treatment. The main side effect noted was infection, but infections did not occur more frequently in patients receiving TCZ as compared to those receiving SOC therapy.
TCZ may be an alternative to SOC for ABMR kidney-transplant patients, either as a first-line treatment or after failure of SOC. Further randomized and controlled studies are needed to support these results.
We systematically reviewed the PubMed literature and reviewed six studies that included 117 patients and collected data on the utilization of TCZ to treat ABMR.
Most studies report a significant reduction in levels of Donor Specific Antibodies (DSAs) and reduced inflammation and microvascular lesions (as found in biopsies). Stabilization of the renal function was observed. Adverse events were light to moderate, and mortality was not linked with TCZ treatment. The main side effect noted was infection, but infections did not occur more frequently in patients receiving TCZ as compared to those receiving SOC therapy.
TCZ may be an alternative to SOC for ABMR kidney-transplant patients, either as a first-line treatment or after failure of SOC. Further randomized and controlled studies are needed to support these results.
摘要：
慢性肾脏疾病（CKD）是一个主要的公共卫生问题，会增加终末期肾脏疾病（ESKD）的风险。心血管疾病,和其他并发症。与透析相比，肾移植是一种肾脏替代疗法，可提供更好的生存率。抗体介导的排斥反应（ABMR）是肾移植后的重要并发症：它有助于短期和长期损伤。标准护理（SOC）疗法结合血浆置换和静脉免疫球蛋白（IVIg），有或没有类固醇，有或没有利妥昔单抗：然而，尽管这种联合治疗，ABMR仍然是移植物丢失的主要原因。IL-6是一种关键的细胞因子：它调节炎症，和发展，成熟,和T细胞的激活，B细胞,和浆细胞。Tocilizumab（TCZ）是针对IL-6R的主要人源化单克隆抗体，并且似乎是在致敏受体中管理ABMR的安全且可能的策略。我们进行了文献综述，以评估抗IL-6R单克隆抗体TCZ在ABMR方案中的位置。
我们系统回顾了PubMed文献，回顾了6项研究，其中包括117名患者，并收集了使用TCZ治疗ABMR的数据。
大多数研究报告供体特异性抗体（DSA）水平显着降低，炎症和微血管病变减少（如活检中发现的）。观察到肾功能的稳定。不良事件为轻度至中度，死亡率与TCZ治疗无关.注意到的主要副作用是感染，但与接受SOC治疗的患者相比,接受TCZ的患者感染发生率并不高.
TCZ可能是ABMR肾移植患者SOC的替代方案，作为一线治疗或SOC失败后。需要进一步的随机对照研究来支持这些结果。
我们系统回顾了PubMed文献，回顾了6项研究，其中包括117名患者，并收集了使用TCZ治疗ABMR的数据。
大多数研究报告供体特异性抗体（DSA）水平显着降低，炎症和微血管病变减少（如活检中发现的）。观察到肾功能的稳定。不良事件为轻度至中度，死亡率与TCZ治疗无关.注意到的主要副作用是感染，但与接受SOC治疗的患者相比,接受TCZ的患者感染发生率并不高.
TCZ可能是ABMR肾移植患者SOC的替代方案，作为一线治疗或SOC失败后。需要进一步的随机对照研究来支持这些结果。
