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免疫检查点抑制剂治疗后急性肾损伤的发生率、死亡率和危险因素:真实世界证据的系统评价和荟萃分析。

Incidence, mortality, and risk factors of acute kidney injury after immune checkpoint inhibitors: Systematic review and meta-analysis of real-world evidence.

机构信息

Department of Rheumatology and Clinical Immunology, Peking University First Hospital, No.8, Xishiku Street, West District, Beijing 100034, China.

Department of Gastroenterology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.

出版信息

Eur J Intern Med. 2023 Sep;115:88-95. doi: 10.1016/j.ejim.2023.05.034. Epub 2023 May 30.


DOI:10.1016/j.ejim.2023.05.034
PMID:37263805
Abstract

BACKGROUND: To precisely quantify the incidence, mortality, and risk factors for acute kidney injury (AKI) following immune checkpoint inhibitor (ICI) treatment for cancer in real-world scenarios. METHODS: Comprehensive searches were performed on PubMed, EMBASE and the Cochrane library. Real-world observational studies reporting incidence, mortality and/or factors for AKI in ICI-treated patients were eligible. Odds ratio (OR) with 95% CI for potential predictors and hazard ratio (HR) with 95% CI for mortality risk associated with AKI were calculated using the random-effect model. RESULTS: Eighteen articles comprising 12,111 patients receiving ICI were finally eligible. The pooled incidence was 16.0% (95% CI 11.2%-20.8%; n = 15) for AKI following ICI therapies overall and 3.5% (95% CI 2.1%-4.9%; n = 8) for ICI-induced AKI. Patients who developed AKI during ICI therapies had 51% increased risk of death compared with those without (HR 1.51, 95% CI 1.07-2.14). Regarding risk factors, statistically increased risk for AKI during ICI therapies was observed with preexisting chronic kidney diseases (OR 1.86, 1.25-2.78), diabetes (OR 1.26, 1.04-1.53), and concomitant extrarenal immune-related adverse events (OR 2.53, 1.79-3.56). Ipilimumab (OR 2.18, 1.43-3.32), combined ICI therapies (OR 1.80, 1.14-2.83) and concomitant use of proton pump inhibitors (OR 1.97, 1.56-2.49), renin-angiotensin system inhibitors (OR 1.50, 1.05-2.14), diuretics (OR 1.69, 1.27-2.26) also significantly predicted the incident AKI. CONCLUSIONS: AKI episode is frequently observed during ICI exposure for cancer treatment, but ICI induced nephrotoxicity is only occasionally. Higher risk of AKI during ICI therapies was significantly associated with specific comorbidities, concomitant of certain drugs, ipilimumab and ICI combination therapies.

摘要

背景:在真实环境中,精确量化癌症免疫检查点抑制剂(ICI)治疗后急性肾损伤(AKI)的发病率、死亡率和危险因素。

方法:在 PubMed、EMBASE 和 Cochrane 图书馆进行全面检索。符合条件的研究为报告 ICI 治疗患者 AKI 发病率、死亡率和/或危险因素的真实世界观察性研究。使用随机效应模型计算潜在预测因素的比值比(OR)及其 95%置信区间(95%CI)和与 AKI 相关的死亡率风险的危害比(HR)及其 95%CI。

结果:最终纳入 18 篇文章,共 12111 例接受 ICI 治疗的患者。ICI 治疗后 AKI 的总体发生率为 16.0%(95%CI 11.2%-20.8%;n=15),ICI 诱导的 AKI 发生率为 3.5%(95%CI 2.1%-4.9%;n=8)。与未发生 AKI 的患者相比,ICI 治疗期间发生 AKI 的患者死亡风险增加 51%(HR 1.51,95%CI 1.07-2.14)。关于危险因素,在 ICI 治疗期间发生 AKI 的风险与慢性肾脏病(OR 1.86,1.25-2.78)、糖尿病(OR 1.26,1.04-1.53)和同时发生的肾脏外免疫相关不良事件(OR 2.53,1.79-3.56)显著相关。Ipilimumab(OR 2.18,1.43-3.32)、联合 ICI 治疗(OR 1.80,1.14-2.83)和同时使用质子泵抑制剂(OR 1.97,1.56-2.49)、肾素-血管紧张素系统抑制剂(OR 1.50,1.05-2.14)、利尿剂(OR 1.69,1.27-2.26)也显著预测 AKI 的发生。

结论:在癌症的 ICI 治疗中经常观察到 AKI 发作,但 ICI 诱导的肾毒性仅偶尔发生。ICI 治疗期间 AKI 的风险较高与特定合并症、某些药物的同时使用、Ipilimumab 和 ICI 联合治疗显著相关。

相似文献

[1]
Incidence, mortality, and risk factors of acute kidney injury after immune checkpoint inhibitors: Systematic review and meta-analysis of real-world evidence.

Eur J Intern Med. 2023-9

[2]
Incidence and risk factors of acute kidney injury in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

Front Immunol. 2023

[3]
Association of Proton Pump Inhibitor Use and Immune Checkpoint Inhibitor-Mediated Acute Kidney Injury: A Meta-Analysis and a Review of Related Outcomes.

Am J Nephrol. 2024

[4]
Incidence, predictors and 6-month overall outcome of acute kidney injury in Chinese patients receiving PD-1 inhibitors.

Future Oncol. 2022-5

[5]
Comparative risk of acute kidney injury among cancer patients treated with immune checkpoint inhibitors.

Cancer Commun (Lond). 2023-2

[6]
Risk factors of immune checkpoint inhibitor-associated acute kidney injury: evidence from clinical studies and FDA pharmacovigilance database.

BMC Nephrol. 2023-4-22

[7]
Incidence, predictors, and survival impact of acute kidney injury in patients with melanoma treated with immune checkpoint inhibitors: a 10-year single-institution analysis.

Oncoimmunology. 2021-5-23

[8]
Acute kidney injury in advanced lung cancer patients treated with PD-1 inhibitors: a single center observational study.

J Cancer Res Clin Oncol. 2023-7

[9]
Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes.

J Immunother Cancer. 2020-6

[10]
All-cause and immune checkpoint inhibitor-associated acute kidney injury in immune checkpoint inhibitor users: a meta-analysis of occurrence rate, risk factors and mortality.

Clin Kidney J. 2023-11-28

引用本文的文献

[1]
Immunotherapy-Associated Renal Dysfunction in Metastatic Cancer: An Emerging Challenge in Onco-Nephrology.

Cancers (Basel). 2025-6-23

[2]
Nephrotoxicity of Immune Checkpoint Inhibitors in Single and Combination Therapy-A Systematic and Critical Review.

Biomedicines. 2025-3-13

[3]
Acute Kidney Injury Associated with Novel Anticancer Therapies: Immunotherapy.

Kidney360. 2025-4-1

[4]
Clinical outcomes after immune checkpoint inhibitor-associated acute kidney injury: a cohort study.

BMJ Open. 2025-2-7

[5]
Acute kidney injury in patients treated with immune checkpoint inhibitors: a single-center retrospective study.

Ren Fail. 2024-12

[6]
Immune checkpoint inhibitors and acute kidney injury.

Front Immunol. 2024-2-23

[7]
Nephrotoxicity in the Age of Immune Checkpoint Inhibitors: Mechanisms, Diagnosis, and Management.

Int J Mol Sci. 2023-12-28

[8]
All-cause and immune checkpoint inhibitor-associated acute kidney injury in immune checkpoint inhibitor users: a meta-analysis of occurrence rate, risk factors and mortality.

Clin Kidney J. 2023-11-28

[9]
Single and combination immunotherapy with chemotherapy and the risk of AKI in patients with solid cancer.

Clin Exp Nephrol. 2024-4

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