Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China.
Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Immunol. 2023 May 29;14:1173952. doi: 10.3389/fimmu.2023.1173952. eCollection 2023.
BACKGROUND: The incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported with their widespread application. OBJECTIVE: This study aimed to quantify the incidence and identify risk factors of AKI in cancer patients treated with ICIs. METHODS: We searched the electronic databases of PubMed/Medline, Web of Science, Cochrane and Embase before 1 February 2023 on the incidence and risk factors of AKI in patients receiving ICIs and registered the protocol in PROSPERO (CRD42023391939). A random-effect meta-analysis was performed to quantify the pooled incidence estimate of AKI, identify risk factors with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) and investigate the median latency period of ICI-AKI in patients treated with ICIs. Assessment of study quality, meta-regression, and sensitivity and publication bias analyses were conducted. RESULTS: In total, 27 studies consisting of 24048 participants were included in this systematic review and meta-analysis. The overall pooled incidence of AKI secondary to ICIs was 5.7% (95% CI: 3.7%-8.2%). Significant risk factors were older age (OR: 1.01, 95% CI: 1.00-1.03), preexisting chronic kidney disease (CKD) (OR: 2.90, 95% CI: 1.65-5.11), ipilimumab (OR: 2.66, 95% CI: 1.42-4.98), combination of ICIs (OR: 2.45, 95% CI: 1.40-4.31), extrarenal immune-related adverse events (irAEs) (OR: 2.34, 95% CI: 1.53-3.59), and proton pump inhibitor (PPI) (OR: 2.23, 95% CI: 1.88-2.64), nonsteroidal anti-inflammatory drug (NSAID) (OR: 2.61, 95% CI: 1.90-3.57), fluindione (OR: 6.48, 95% CI: 2.72-15.46), diuretic (OR: 1.78, 95% CI: 1.32-2.40) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) (pooled OR: 1.76, 95% CI: 1.15-2.68) use. Median time from ICIs initiation to AKI was 108.07 days. Sensitivity and publication bias analyses indicated robust results for this study. CONCLUSION: The occurrence of AKI following ICIs was not uncommon, with an incidence of 5.7% and a median time interval of 108.07 days after ICIs initiation. Older age, preexisting chronic kidney disease (CKD), ipilimumab, combined use of ICIs, extrarenal irAEs, and PPI, NSAID, fluindione, diuretics and ACEI/ARB use are risk factors for AKI in patients receiving ICIs. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42023391939.
背景：免疫检查点抑制剂（ICI）广泛应用于恶性肿瘤患者，其导致急性肾损伤（AKI）的发生率和风险因素也被广泛报道。 目的：本研究旨在定量评估癌症患者接受 ICI 治疗后 AKI 的发生率，并确定其风险因素。 方法：我们在 2023 年 2 月 1 日前检索了 PubMed/Medline、Web of Science、Cochrane 和 Embase 电子数据库，以获取有关接受 ICI 治疗的患者 AKI 发生率和风险因素的研究，并在 PROSPERO（CRD42023391939）中注册了方案。采用随机效应荟萃分析来量化 AKI 的汇总发生率，识别风险因素的汇总优势比（OR）和 95%置信区间（95%CI），并研究接受 ICI 治疗的患者 ICI-AKI 的中位潜伏期。进行了研究质量评估、meta 回归、敏感性和发表偏倚分析。 结果：共纳入 27 项研究，包含 24048 名参与者，这些研究均被纳入本系统评价和荟萃分析。ICI 引起 AKI 的总体汇总发生率为 5.7%（95%CI：3.7%-8.2%）。显著的风险因素包括年龄较大（OR：1.01，95%CI：1.00-1.03）、预先存在的慢性肾脏病（CKD）（OR：2.90，95%CI：1.65-5.11）、伊匹单抗（OR：2.66，95%CI：1.42-4.98）、ICI 联合使用（OR：2.45，95%CI：1.40-4.31）、肾外免疫相关不良事件（irAE）（OR：2.34，95%CI：1.53-3.59）、质子泵抑制剂（PPI）（OR：2.23，95%CI：1.88-2.64）、非甾体抗炎药（NSAID）（OR：2.61，95%CI：1.90-3.57）、氟苯达嗪（OR：6.48，95%CI：2.72-15.46）、利尿剂（OR：1.78，95%CI：1.32-2.40）和血管紧张素转换酶抑制剂（ACEI）或血管紧张素受体阻滞剂（ARB）（汇总 OR：1.76，95%CI：1.15-2.68）的使用。从 ICI 开始到 AKI 的中位时间为 108.07 天。敏感性和发表偏倚分析表明，本研究结果稳健。 结论：ICI 后 AKI 的发生并不罕见，发生率为 5.7%，ICI 后中位时间间隔为 108.07 天。年龄较大、预先存在的 CKD、伊匹单抗、ICI 联合使用、肾外 irAE、PPI、NSAID、氟苯达嗪、利尿剂和 ACEI/ARB 的使用是接受 ICI 治疗的患者发生 AKI 的风险因素。 系统评价注册：https://www.crd.york.ac.uk/prospero/，标识符 CRD42023391939。
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