Department of Medicine, University of Sydney Nepean Clinical School, Kingswood, New South Wales, Australia.
Department of Nephrology, Nepean Hospital, Kingswood, New South Wales, Australia.
Clin J Am Soc Nephrol. 2023 Jul 1;18(7):843-849. doi: 10.2215/CJN.0000000000000160. Epub 2023 Mar 31.
The blockade of immune regulatory sites, cytotoxic T-lymphocyte antigen 4, programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) with immune checkpoint inhibitors has revolutionized survival outcomes in patients with cancer. However, immune checkpoint inhibitors are associated with a range of immune-related adverse events. The aim of this network meta-analysis was to evaluate severe adverse kidney events in patients with oncological or hematological malignancy receiving monotherapy, dual therapy, or combined therapy treatment with immune checkpoint inhibitors when compared with either placebo or standard chemotherapy.
Phase 3 randomized control trials reporting severe grade (3-5) adverse kidney events were identified across five electronic databases from inception to May 2022. This was supplemented with hand searching of medical journals and the National Clinical Trials registry. A Bayesian network meta-analysis was performed for AKI, hypertension, CKD, and the composite of all acute kidney adverse events. The results are reported as per the PRISMA guidelines.
Ninety-five randomized control trials reported severe grade adverse kidney events. The risk of developing severe AKI is higher among patients who received PD-1 plus chemotherapy (odds ratio [OR], 1.8; 95% credible interval [CrI], 1.4 to 2.5) and PD-L1 plus chemotherapy (OR, 1.8; 95% CrI, 1.2 to 2.7) compared with standard chemotherapy and placebo (94 studies, 63,357 participants). The risk of developing the composite of all severe acute kidney adverse events is higher among patients who received PD-1 plus chemotherapy (OR, 1.6; 95% CrI, 1.1 to 2.3) and PD-L1 plus chemotherapy (OR, 1.7; 95% CrI, 1.1 to 2.8) when compared with standard chemotherapy and placebo (95 studies, 63,973 participants).
The combined regimen of PD-1 plus chemotherapy and PD-L1 plus chemotherapy was associated with higher incidence of severe AKI and the composite of all severe acute kidney adverse events.
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_07_10_CJN0000000000000160.mp3.
免疫检查点抑制剂阻断免疫调节部位、细胞毒性 T 淋巴细胞抗原 4、程序性细胞死亡 1（PD-1）和程序性细胞死亡配体 1（PD-L1），彻底改变了癌症患者的生存结果。然而，免疫检查点抑制剂与一系列免疫相关不良事件相关。本网络荟萃分析旨在评估接受免疫检查点抑制剂单药、双药或联合治疗的肿瘤或血液恶性肿瘤患者与安慰剂或标准化疗相比严重肾脏不良事件。
从五个电子数据库中检索了从开始到 2022 年 5 月报告严重（3-5 级）不良肾脏事件的 3 期随机对照试验。这通过对医学期刊和国家临床试验注册中心的手工搜索进行了补充。对 AKI、高血压、CKD 和所有急性肾脏不良事件的综合进行了贝叶斯网络荟萃分析。结果按照 PRISMA 指南进行报告。
95 项随机对照试验报告了严重的肾脏不良事件。与标准化疗和安慰剂相比，接受 PD-1 联合化疗（比值比 [OR]，1.8；95%可信区间 [CrI]，1.4 至 2.5）和 PD-L1 联合化疗（OR，1.8；95% CrI，1.2 至 2.7）的患者发生严重 AKI 的风险更高（94 项研究，63357 名参与者）。与标准化疗和安慰剂相比，接受 PD-1 联合化疗（OR，1.6；95% CrI，1.1 至 2.3）和 PD-L1 联合化疗（OR，1.7；95% CrI，1.1 至 2.8）的患者发生所有严重急性肾脏不良事件的综合风险更高（95 项研究，63973 名参与者）。
PD-1 联合化疗和 PD-L1 联合化疗联合方案与严重 AKI 和所有严重急性肾脏不良事件的综合发生有关。
