Isik Busra, Alexander Mariam P, Manohar Sandhya, Vaughan Lisa, Kottschade Lisa, Markovic Svetomir, Lieske John, Kukla Aleksandra, Leung Nelson, Herrmann Sandra M
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Kidney Int Rep. 2021 Feb 2;6(4):1022-1031. doi: 10.1016/j.ekir.2021.01.013. eCollection 2021 Apr.
Immune checkpoint inhibitors (ICIs) are effective in treating several cancers; however, acute kidney injury (AKI) can occur as part as an immune-related adverse event (iRAE). Biomarkers at the time of AKI diagnosis may help determine whether they are ICI- related and guide therapeutic strategies.
In this retrospective study, we reviewed patients with cancer treated with ICI therapy between 2014 and 2020 who developed AKI (defined as a ≥1.5-fold increase in serum creatinine [SCr]) that was attributed to ICI (ICI-AKI) and compared them with an adjudicated non-ICI-AKI group. Clinical and laboratory features, including SCr, serum C-reactive protein (CRP), and urine retinol binding protein/urine creatinine (uRBP/Cr) levels at AKI event were evaluated.
There were 37 patients with ICI-AKI and 13 non-ICI-AKI referents in the cohort for analysis. At time of AKI, SCr, CRP, and uRBP/Cr were significantly higher in the ICI-AKI compared with the non-ICI-AKI patients (median [interquartile range (IQR)] SCr 2.0 [1.7, 2.9] vs. 1.5 [1.3, 1.6] mg/dl, serum CRP 54.0 [33.7, 90.0] vs. 3.5 [3.0, 7.9] mg/l, and uRBP/Cr 1927 [1174, 46,522] vs. 233 [127, 989] μg/g Cr, respectively, < 0.05 for all). Compared with the referent group, time from ICI initiation to AKI was shorter in the ICI-AKI patients. Among the ICI-AKI group, complete renal recovery occurred in 39% of patients by 3 months; rechallenge occurred in 16 (43%) of patients, of whom 3 (19%) had recurrence of AKI.
Our findings suggest that serum CRP and uRBP/Cr may help to differentiate AKI due to ICI from other causes.
免疫检查点抑制剂（ICI）在治疗多种癌症方面有效；然而，急性肾损伤（AKI）可能作为免疫相关不良事件（iRAE）的一部分发生。AKI诊断时的生物标志物可能有助于确定其是否与ICI相关，并指导治疗策略。
在这项回顾性研究中，我们回顾了2014年至2020年间接受ICI治疗且发生AKI（定义为血清肌酐[SCr]升高≥1.5倍）且归因于ICI（ICI-AKI）的癌症患者，并将他们与经判定的非ICI-AKI组进行比较。评估了临床和实验室特征，包括AKI事件时的SCr、血清C反应蛋白（CRP）和尿视黄醇结合蛋白/尿肌酐（uRBP/Cr）水平。
队列中有37例ICI-AKI患者和13例非ICI-AKI对照者用于分析。在AKI发生时，与非ICI-AKI患者相比，ICI-AKI患者的SCr、CRP和uRBP/Cr显著更高（中位数[四分位间距（IQR）]，SCr分别为2.0[1.7,2.9]与1.5[1.3,1.6]mg/dl，血清CRP为54.0[33.7,90.0]与3.5[3.0,7.9]mg/l，uRBP/Cr为1927[1174,46522]与233[127,989]μg/g Cr，所有P均<0.05）。与对照组相比，ICI-AKI患者从ICI开始至AKI的时间更短。在ICI-AKI组中，39%的患者在3个月时完全肾功能恢复；16例（43%）患者再次接受ICI治疗，其中3例（19%）发生AKI复发。
我们的研究结果表明，血清CRP和uRBP/Cr可能有助于将ICI引起的AKI与其他原因区分开来。
