免疫检查点抑制剂（ICIs）可以引起惊人的抗肿瘤反应，但可能导致与ICI治疗相关的急性肾损伤（AKI-ICI）。目前缺乏可以区分AKI-ICI和其他原因引起的AKI（AKI-other）的生物标记。因为ICIs阻碍免疫调节途径，我们假设与免疫细胞失调相关的生物标记，包括系统循环和肾组织中的肿瘤坏死因子α（TNF-α）和B和T细胞激活的其他标志物，可能有助于诊断AKI-ICI。这是一项前瞻性研究，共有24名在ICI治疗期间出现AKI的参与者，被鉴定为患有AKI-ICI（n = 14）或AKI-other（n = 10）。我们比较了肾脏炎症和损伤的指标（中性粒细胞凝胶酶相关脂蛋白、肾损伤分子1），以及T细胞相关的细胞因子（TNF-α、干扰素-γ、白细胞介素(IL)-2、IL-4、IL-6、IL-8、IL-9和IL-10）的血浆和尿液水平。我们还使用质谱细胞术系统比较了系统循环和肾组织中的T细胞反应。我们发现，在发生AKI-ICI的患者中，肾组织中包括CD4存储细胞、T辅助细胞和树突状细胞在内的特定免疫细胞以及尿液细胞因子IL-2、IL-10和TNF-α增加，与患有AKI-other的患者相比明显增加（P＜0.05）。TNF-α在区分AKI原因方面的判别能力较强（曲线下面积=0.814，95%置信区间：0.623-1.00）。CD4+ T细胞具有记忆表型的亚群是主要的。这些结果表明，特定的T细胞反应及其相关的细胞因子可能是与ICI治疗相关的AKI的指示，并可能有助于区分AKI-ICI和AKI-other。尿中的TNF-α是一种有前途的AKI-ICI生物标记，最常见于急性间质性肾炎（AIN），TNF-α途径可能成为治疗干预的潜在靶点。©2022 Elsevier。

Immune checkpoint inhibitors (ICIs) induce impressive antitumor responses but may lead to acute kidney injury (AKI) associated with ICI therapy (AKI-ICI). Biomarkers distinguishing AKI-ICI from AKI because of other causes (AKI-other) are currently lacking. Because ICIs block immunoregulatory pathways, we hypothesized that biomarkers related to immune cell dysregulation, including tumor necrosis factor alpha (TNF-α) and other markers of B and T cell activation in the systemic circulation and kidney tissue, may aid with the diagnosis of AKI-ICI.This is a prospective study consisting of 24 participants who presented with AKI during ICI therapy, adjudicated to either have AKI-ICI (n = 14) or AKI-other (n = 10). We compared markers of kidney inflammation and injury (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1) as well as plasma and urine levels of T cell-associated cytokines (TNF-α, interferon-γ, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-9, and IL-10) between groups. We also compared T-cell responses in the systemic circulation and in kidney tissue across groups, using mass cytometry systems.We observed increase in several specific immune cells, including CD4 memory, T helper cells, and dendritic cells in the kidney tissue, as well as in the urine cytokines IL-2, IL-10, and TNF-α, in patients who developed AKI-ICI compared to patients with AKI-other (P < 0.05 for all). The discriminatory ability of TNF-α on AKI cause was strong (area under the curve = 0.814, 95% confidence interval: 0.623-1.00. The CD4+ T cells with memory phenotype formed the dominant subset.These results suggest that specific T-cell responses and their respective cytokines may be indicative of AKI associated with ICI therapy and may help to differentiate AKI-ICI from AKI-other. Urine TNF-α is a promising biomarker for AKI-ICI, which is most often caused by acute interstitial nephritis (AIN), and TNF-α pathway may serve as a potential target for therapeutic intervention.© 2022 Published by Elsevier Inc. on behalf of the International Society of Nephrology.