澳大利亚非小细胞肺癌患者的免疫相关性急性肾损伤：真实世界研究结果。

Immune-related acute kidney injury in Australian non-small cell lung cancer patients: Real-world results.

机构信息

Department of Medical Oncology, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia.

出版信息

Lung Cancer. 2023 Oct;184:107325. doi: 10.1016/j.lungcan.2023.107325. Epub 2023 Aug 9.

DOI:10.1016/j.lungcan.2023.107325

PMID:37573702

Abstract

BACKGROUND

The use of immune checkpoint inhibitors has altered therapeutic paradigms in NSCLC. However, they may cause immune-related toxicities, including acute kidney injury (irAKI), especially when combined with nephrotoxic agents. We investigated the incidence, management and outcomes of AKI in Australian NSCLC patients.

METHODS

Medical records from a cancer centre registry were reviewed. AKI was defined and graded on absolute creatinine rise, or rise above baseline. Fishers exact test compared proportions. The Kaplan-Meier method estimated survival, and multiple logistic regression tested for risk factors.

RESULTS

Of 449 patients who underwent immunotherapy from 2013 to 2021, the median age was 65 years and 61% were male. Metastatic disease was present in 68% at diagnosis, the remainder had stage Ia-III disease; 70% had adenocarcinoma; and 17% had EGFR mutations. AKI was identified in 65 patients (14.5%) of which 19 were irAKI (4.2%). Within irAKI patients, eleven (58%) had other immune-related adverse events. Median time to irAKI onset was 4 months (IQR 4-6). Seventeen (89%) patients had AKI stage 1 or 2; two had stage 3. Eleven patients developed chronic kidney disease; none required renal replacement therapy. Kidney biopsies demonstrated acute interstitial nephritis (n = 3), acute tubular necrosis (n = 1) and anti-phospholipase A2 receptor negative membranous glomerulonephritis (n = 1). Five patients were rechallenged with immunotherapy; two had recurrent irAKI. The median overall survival for those with irAKI was not reached versus 12 months with no irAKI (HR 0.35, 95 %CI 0.20-0.60, p = 0.01). Risk factors for irAKI included having an additional, non-renal irAE (OR 6.21, 95 %CI 2.35-17.26, p ≤ 0.01); immunotherapy combined with other cancer therapies (OR 5.62, 95 %CI 2.08-16.20, p ≤ 0.01); and ECOG performance status > 1 (OR 4.39 (95 %CI 1.11-14.90, p = 0.02) CONCLUSIONS: The incidence of irAKI was similar to the published literature. Renal recovery was poor, however survival was not compromised. Improved diagnostic and therapeutic strategies for irAKI would benefit this population.

摘要

背景

免疫检查点抑制剂的使用改变了 NSCLC 的治疗模式。然而，它们可能会引起免疫相关的毒性，包括急性肾损伤（irAKI），特别是当与肾毒性药物联合使用时。我们研究了澳大利亚 NSCLC 患者 AKI 的发生率、管理和结局。

方法

从癌症中心的病历中进行了回顾性研究。AKI 的定义和分级采用绝对肌酐升高或高于基线的标准。Fisher 精确检验比较了比例。Kaplan-Meier 方法估计了生存率，多因素逻辑回归检验了危险因素。

结果

在 2013 年至 2021 年间接受免疫治疗的 449 名患者中，中位年龄为 65 岁，61%为男性。诊断时 68%有转移性疾病，其余为 I 期-III 期疾病；70%为腺癌；17%有 EGFR 突变。在 65 名（14.5%）患者中发现了 AKI，其中 19 名（4.2%）为 irAKI。在 irAKI 患者中，11 名（58%）有其他免疫相关的不良反应。irAKI 发病的中位时间为 4 个月（IQR 4-6）。17 名（89%）患者的 AKI 为 1 期或 2 期；2 名患者为 3 期。11 名患者发生慢性肾脏病；均未进行肾脏替代治疗。肾活检显示急性间质性肾炎（n=3）、急性肾小管坏死（n=1）和抗磷脂酶 A2 受体阴性膜性肾小球肾炎（n=1）。5 名患者再次接受免疫治疗；2 名患者出现复发性 irAKI。irAKI 患者的中位总生存期未达到，而无 irAKI 患者的中位总生存期为 12 个月（HR 0.35，95%CI 0.20-0.60，p=0.01）。irAKI 的危险因素包括存在其他非肾脏的 irAE（OR 6.21，95%CI 2.35-17.26，p≤0.01）；免疫治疗联合其他癌症治疗（OR 5.62，95%CI 2.08-16.20，p≤0.01）；ECOG 表现状态>1（OR 4.39（95%CI 1.11-14.90，p=0.02）。