Section of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Clinical and Translational Research Accelerator, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
J Immunother Cancer. 2022 Mar;10(3). doi: 10.1136/jitc-2021-004421.
In patients receiving immune checkpoint inhibitor (ICI) therapy, acute kidney injury (AKI) is common, and can occur either from kidney injury unrelated to ICI use or from immune activation resulting in acute interstitial nephritis (AIN). In this study, we test the hypothesis that occurrence of AIN indicates a favorable treatment response to ICI therapy and therefore among patients who develop AKI while on ICI therapy, those with AIN will demonstrate greater survival compared with others with AKI.
In this observational cohort study, we included participants initiated on ICI therapy between 2013 and 2019. We tested the independent association of AKI and estimated AIN (eAIN) with mortality up to 1 year after therapy initiation as compared with those without AKI using time-varying Cox proportional hazard models controlling for demographics, comorbidities, cancer type, stage, and therapy, and baseline laboratory values. We defined eAIN as those with a predicted probability of AIN >90th percentile derived from a recently validated diagnostic model.
Of 2207 patients initiated on ICIs, 617 (28%) died at 1 year and 549 (25%) developed AKI. AKI was independently associated with higher mortality (adjusted HR, 2.28 (95% CI 1.90 to 2.72)). Those AKI patients with eAIN had more severe AKI as reflected by a higher peak serum creatinine (3.3 (IQR 2.1-6.1) vs 1.4 (1.2-1.9) mg/dL, p<0.001) but exhibited lower mortality than those without eAIN in univariable analysis (HR 0.43 (95% CI 0.21 to 0.89)) and after adjusting for demographics, comorbidities, and cancer type and severity (adjusted HR 0.44 (95% CI 0.21 to 0.93)).
In patients treated with ICI, mortality was higher in those with AKI unrelated to ICI but lower in those where the underlying etiology was AIN. Future studies could evaluate the association of biopsy-proven or biomarker-proven AIN with mortality in those receiving ICI therapy.
在接受免疫检查点抑制剂（ICI）治疗的患者中，急性肾损伤（AKI）很常见，其可能由与 ICI 使用无关的肾损伤引起，也可能由免疫激活引起急性间质性肾炎（AIN）。在这项研究中，我们验证了以下假说，即 AIN 的发生表明对 ICI 治疗有良好的治疗反应，因此，在接受 ICI 治疗的患者中发生 AKI 的患者中，AIN 患者的生存情况要好于其他 AKI 患者。
在这项观察性队列研究中，我们纳入了 2013 年至 2019 年期间开始接受 ICI 治疗的参与者。我们使用时变 Cox 比例风险模型，通过控制人口统计学、合并症、癌症类型、分期和治疗以及基线实验室值，测试 AKI 和估计的 AIN（eAIN）与治疗开始后 1 年内死亡的独立关联，与无 AKI 的患者进行比较。我们将 eAIN 定义为从最近验证的诊断模型中获得的 AIN 预测概率 >90 百分位数的患者。
在 2207 名开始接受 ICI 治疗的患者中，有 617 名（28%）在 1 年内死亡，549 名（25%）发生 AKI。AKI 与更高的死亡率独立相关（调整后的 HR，2.28（95%CI 1.90 至 2.72））。那些患有 eAIN 的 AKI 患者的 AKI 更严重，表现为更高的峰值血清肌酐（3.3（IQR 2.1-6.1）vs 1.4（1.2-1.9）mg/dL，p<0.001），但在单变量分析中死亡率低于无 eAIN 的患者（HR 0.43（95%CI 0.21 至 0.89）），并且在调整人口统计学、合并症和癌症类型和严重程度后（调整后的 HR 0.44（95%CI 0.21 至 0.93））。
在接受 ICI 治疗的患者中，与 ICI 无关的 AKI 患者的死亡率较高，而病因是 AIN 的患者的死亡率较低。未来的研究可以评估在接受 ICI 治疗的患者中，经活检证实或生物标志物证实的 AIN 与死亡率的关系。
