与免疫检查点抑制剂（ICI-AIN）相关的急性间质性肾炎（AIN）的病理生理学尚不完全清楚。我们的目标是分析区分急性肾小管坏死 (ATN) 和 AIN 的可能生物标志物，特别是在癌症患者中，并研究免疫检查点通路在 ICI-AIN 中的参与。我们进行了一项观察性研究。我们招募了 ICI-AIN 事件诊断的患者 (n = 19)。我们在诊断时测量了血清和尿液中的可溶性 PD-1 (sPD-1)、sPD-L1 和 sPD-L2，并与非 ICI 相关 AIN (非 ICI-AIN) 患者进行了比较 (n = 18)和 ATN（n = 21）。研究结果在另一家机构的独立队列中得到了验证（n = 30）。此外，我们对 ICI-AIN 患者的肾活检进行了 PD-L1 和 PD-L2 免疫染色，并与非 ICI-AIN 患者进行了比较。与 ATN 患者相比，AIN 患者的尿液 sPD-1 (usPD-1) 较高（P=.03）。 AIN 患者的血清 sPD-1 (ssPD-1) 水平也高于 ATN 患者 (P = .021)。 在癌症患者中，usPD-1 <129.3 pg/ml 区分 ATN 和 ICI-AIN 的敏感性为 71.43%，特异性为 94.44%，似然比为 12.86。在外部验证队列中，相同的截止值显示敏感性为 80%。 在肾活检中，ICI-AIN 患者的 PD-L1 阳性肾小管密度高于非 ICI-AIN 患者 (P = .02)。与非 ICI-AIN 患者相比，ICI-AIN 患者中具有 >2.64/mm2 PD-L2 阳性肾小管的患者比例较高 (P = .034)。 usPD-1与PD-L1阳性小管数量呈正相关（P=.009，r=0.72）。AIN中UsPD-1和ssPD-1的含量高于ATN。此外，usPD-1和肾小管PD-L1表达之间存在很强的相关性。我们的研究结果表明，usPD-1 作为非侵入性生物标志物可区分 ICI-AIN 和 ATN，尤其是在癌症患者中，这一点已在外部验证队列中得到证实。© 作者 2024。由牛津大学出版社出版代表 ERA。

Acute interstitial nephritis (AIN) related to immune checkpoint inhibitors (ICI-AIN) has a not completely understood pathophysiology. Our objectives were to analyze possible biomarkers for the differentiation between acute tubular necrosis (ATN) and AIN, especially in cancer patients, and to study the participation of the immune checkpoint pathway in ICI-AIN.We performed an observational study. We recruited patients with incident diagnosis of ICI-AIN (n = 19). We measured soluble PD-1 (sPD-1), sPD-L1, and sPD-L2 in serum and urine at diagnosis and compared to it patients with non-ICI-related AIN (non-ICI-AIN) (n = 18) and ATN (n = 21). The findings were validated in an independent cohort from another institution (n = 30). Also, we performed PD-L1 and PD-L2 immunostaining of kidney biopsies from patients with ICI-AIN and compared to patients with non-ICI-AIN.Urinary sPD-1 (usPD-1) was higher in patients with AIN compared to ATN (P = .03). Patients with AIN also showed higher serum sPD-1 (ssPD-1) than patients with ATN (P = .021). In cancer patients, usPD-1 <129.3 pg/ml had a 71.43% sensitivity and 94.44% specificity to differentiate ATN from ICI-AIN, with a likelihood ratio of 12.86. In the external validation cohort, the same cutoff showed a sensitivity of 80%. In kidney biopsies, patients with ICI-AIN showed higher density of PD-L1 positive tubules than patients with non-ICI-AIN (P = .02). The proportion of patients having >2.64/mm2 PD-L2 positive tubules was higher among patients with ICI-AIN compared to non-ICI-AIN (P = .034). There was a positive correlation (P = .009, r = 0.72) between usPD-1 and the number of PD-L1 positive tubules.UsPD-1 and ssPD-1 are higher in AIN than ATN. Moreover, there was a strong correlation between usPD-1 and renal tubular PD-L1 expression. Our findings suggest a role of usPD-1 as non-invasive biomarker to differentiate ICI-AIN from ATN, especially in cancer patients, which has been confirmed in an external validation cohort.© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.