原发性非小细胞肺癌患者PD-1/PD-L1抑制剂相关急性肾损伤的临床特征分析

Clinical investigation of PD-1/PD-L1 inhibitors associated acute renal injury in patients with primary nonsmall cell lung cancer

目的 探讨原发性非小细胞肺癌(NSCLC)患者发生程序性细胞死亡蛋白1(PD-1)和程序性细胞死亡蛋白配体-1(PD-L1)抑制剂相关急性肾损伤(AKI)的相关因素。方法 本研究采用回顾性病例对照研究,共纳入103例接受PD-1/PD-L1抑制剂治疗的原发性NSCLC患者,将患者分为PD-1/PD-L1抑制剂相关AKI组24例和对照组79例。比较AKI组与对照组患者的基本临床特征,采用多因素Logistic回归分析评估PD-1/PD-L1抑制剂相关AKI发生的风险因素。结果 PD-1/PD-L1抑制剂相关AKI组的患者中合并糖尿病和应用利尿剂、非甾体类抗炎药物(NASIDs)、质子泵抑制剂(PPIs)的比例显著高于对照组,基线肾小球滤过率(e GFR)水平显著低于对照组,PD-1/PD-L1抑制剂使用后出现无菌性白细胞尿、血嗜酸性粒细胞计数增多和肾外免疫相关不良事件(ir AEs)的患者比例显著高于对照组(均P<0.05)。多因素Logistic回归分析结果显示,基线e GFR降低(OR=0.968,95%CI:0.946~0.990,P=0.005)、无菌性白细胞尿(OR=7.618,95%CI:1.406~41.282,P=0.019)、血嗜酸性粒细胞计数增多(OR=24.513,95%CI:2.214~271.463,P=0.009)和合并肾外ir AEs(OR=7.712,95%CI:2.068~24.460,P=0.002)与PD-1/PD-L1抑制剂相关AKI的发生显著相关。结论 原发性NSCLC患者接受PD-1/PD-L1抑制剂治疗后AKI并不少见,对于存在基线肾功能水平下降及治疗后出现无菌性白细胞尿、血嗜酸性粒细胞计数增多和ir AEs的患者,应高度警惕AKI的发生。

Objective To determine the clinical features of programmed cell death protein-1( PD-1) or programmed death ligand-1( PD-L1) inhibitors associated with acute kidney injury( AKI) in patients with primary non-small cell lung cancer( NSCLC).Methods The clinical data of 103 patients with primary non-small cell lung cancer treated with PD-1/PD-L1 inhibitors were collected in this retrospective case-control study,which included 24 patients in the PD-1/PD-L1 inhibitor-related AKI group and 79 patients in the control group. The clinical characteristics of the two groups were compared and the risk factors of PD-1/PD-L1 inhibitors related to AKI were analyzed by multivariate logistic regression model. Results Patients in the AKI group were characterized by higher proportions of diabetes,diuretics use,nonsteroidal anti inflammatory drugs( NSAIDs) use,proton pump inhibitors( PPIs) use,aseptic leukocyturia,blood eosinophil count > 500/μl,combined immune-related adverse events( ir AEs),and a lower baseline estimated glomerular filtration rate( e GFR) level( P < 0. 05). Multivariate logistic regression results showed that decreased baseline e GFR level( OR = 0. 968,95% CI: 0. 946-0. 990,P = 0. 005),aseptic leukocyturia( OR = 7. 618,95% CI: 1. 406-41. 282,P =0. 019),increased blood eosinophil count( OR = 24. 513,95% CI: 2. 214-271. 463,P = 0. 009) and combined other ir AEs( OR =7. 712,95%CI: 2. 068-24. 460,P = 0. 002) were associated with PD-1/PD-L1 inhibitors related AKI. Conclusion PD-1/PD-L1inhibitors associated AKI is not an uncommon complication in primary NSCLC patients receiving PD-1/PD-L1 inhibitors treatment.Patients with decreased baseline renal function,increased blood eosinophil count,aseptic leukocyturia and other ir AEs after treatment should be alert to PD-1/PD-L1 inhibitors associated AKI.