与抗PD-1和抗PD-L1药物相关的急性肾损伤:随机临床试验荟萃分析。

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Isabela Gonçalves Lima, Isabele Benck Usiro Cabral da Silva, Vitória Carpentieri Pípolo, Vinicius Daher Alvares Delfino, Paulo Roberto Bignardi
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引用次数: 0

摘要

背景:免疫检查点抑制剂(ICI免疫检查点抑制剂(ICI)已被广泛用于治疗不同类型的癌症。它们提高了许多肿瘤患者的生存率,并实现了癌症特异性治疗。急性肾损伤(AKI)是与使用 ICI 相关的不良反应之一,其发病率和肾组织学结果仍有待讨论:因此,本荟萃分析评估了 ICI 的使用与 AKI 之间的关联:方法:在 PubMed、Lilacs 和 Cochrane 平台上进行检索。结果:共有 16 项研究符合既定的研究标准:结果:共有 16 项研究符合既定的 PICOT 标准,被纳入本综述。将 ICI 加化疗与单独化疗进行比较,使用 ICI 时发生 AKI 的相对风险 (RR) 为 2.89(95%CI 1.37-6.10)。在按类别和药物类型进行的分析中,程序性细胞死亡1单克隆抗体(抗PD-1)显示发生AKI的风险增加2.11(95%CI 1.26-3.52),而pembrolizumab显示发生AKI的风险(RR= 2.77,95%CI 1.46-5.26)。同样,就 AKI 的严重程度而言,ICI 加化疗组与化疗组相比,AKI 3 级或以上更为常见:3.66(95%CI 1.19-11.30),而亚组分析汇总了对照组中单用 ICI 与单用化疗的比较研究,并未显示出与 AKI 的关联:这些研究结果表明,ICI的使用与AKI风险的增加有关,而与程序性细胞死亡配体1单克隆抗体(抗PD-L1)相比,抗PD-1的使用与更高的肾脏不良事件发生率有关。有必要对急性间质性肾炎(如今被认为是与 ICI 相关的 AKI 的同义词)进行研究,研究应具有足够的功率和明确的标准。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Acute kidney injury associated with anti-PD-1 and anti-PD-L1 drugs: a meta-analysis of randomized clinical trials.

Background: Immune Checkpoint Inhibitors (ICI) have been widely used in treating different types of cancer. They increase survival in many oncologic patients and enable cancer-specific therapy. Acute Kidney Injury (AKI) is one of the adverse effects associated with using ICI, where knowledge of the prevalence and renal histological findings are still reasons for discussion.

Objective: Therefore, this meta-analysis evaluates the association between ICI use and AKI.

Methods: The search was performed in PubMed, Lilacs, and Cochrane platforms. Studies published up to December 1, 2022, were included.

Results: A total of 16 studies met the established PICOT criteria and were included in this review. Comparing the ICI plus chemotherapy against chemotherapy alone, the relative risk (RR) for AKI's development with ICI use was 2.89 (95%CI 1.37-6.10). In the analyses by class and drug type, programmed cell death 1 monoclonal antibody (anti-PD-1) showed an increased risk of 2.11 (95%CI 1.26-3.52), and pembrolizumab demonstrated a risk of AKI (RR= 2.77, 95%CI 1.46-5.26). Likewise, regarding the severity of AKI, AKI grade 3 or higher was more common in the ICI plus chemotherapy compared to the chemotherapy group: 3.66 (95%CI 1.19-11.30), while the subgroup analyses pooled studies comparing ICI alone versus chemotherapy alone in the control group did not demonstrate an association with AKI.

Conclusions: These findings suggest that ICI use is associated with an increased risk of AKI and that anti-PD-1 use is associated with a higher incidence of renal adverse events than programmed cell death ligand 1 monoclonal antibody (anti-PD-L1). Studies with adequate power and well-defined criteria for acute interstitial nephritis, nowadays taken as a synonym for AKI related to ICI, are necessary.

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来源期刊
CiteScore
5.40
自引率
0.00%
发文量
133
审稿时长
4-8 weeks
期刊介绍: The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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