Uchino Tomonobu, Iwano Yuna, Miyazaki Yasunori, Nakajo Michiaki, Osawa Misa, Nagai Erina, Taki Yusuke, Sato Shinsuke, Watanabe Masaya, Takagi Masakazu, Kagawa Yoshiyuki
Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Cancer Chemother Pharmacol. 2024 Dec 23;95(1):11. doi: 10.1007/s00280-024-04737-6.
Cisplatin (CDDP) induces acute kidney injury (AKI) as a side effect during neoadjuvant chemotherapy (NAC). Urinary vanin-1 excretion may increase during CDDP treatment. We investigated whether urinary vanin-1 is an early biomarker for CDDP-induced AKI.
Thirty patients were administered 80 mg/m CDDP on day 1 as NAC for esophageal cancer. Blood and urine samples were collected on days 1, 2, 3, 4, and 6 after CDDP administration. Serum creatinine (sCr) and urinary vanin-1 levels were measured. Creatinine clearance (cCr) and estimated glomerular filtration rate (eGFR) were calculated from sCr. Based on the change in sCr after CDDP administration, the AKI and non-AKI groups were defined using the Kidney Disease Improving Global Outcomes classification. Changes in sCr, cCr, eGFR, and urinary vanin-1 levels were compared between the two groups.
A gradual increase in sCr and a decrease in eGFR were observed over time post-CDDP administration, with differences between the two groups becoming significant by day 4. However, urinary vanin-1 levels increased on day 3 after CDDP administration, and the difference between the two groups was significant on day 3. Receiver operating characteristic curves of urinary vanin-1 on day 3 revealed that a cut-off value of 3.17 ng urinary vanin-1/mg urinary creatinine yielded an area under the curve, sensitivity, and specificity of 0.83 (P < 0.05), 75.0%, and 22.7%, respectively. The non-AKI incidence below the cut-off value of urinary vanin-1 of 3.17 ng/mg uCr was 89.5%.
Urinary vanin-1 is a superior minimally invasive biomarker for the early prediction of CDDP-induced AKI.
顺铂（CDDP）在新辅助化疗（NAC）期间会引起急性肾损伤（AKI）这一副作用。在CDDP治疗期间，尿香草扁桃酸-1排泄量可能会增加。我们研究了尿香草扁桃酸-1是否为CDDP诱导的AKI的早期生物标志物。
30例患者在第1天接受80mg/m²的CDDP作为食管癌的NAC治疗。在CDDP给药后的第1、2、3、4和6天采集血液和尿液样本。测量血清肌酐（sCr）和尿香草扁桃酸-1水平。根据sCr计算肌酐清除率（cCr）和估算肾小球滤过率（eGFR）。根据CDDP给药后sCr的变化，使用改善全球肾脏病预后组织的分类方法定义AKI组和非AKI组。比较两组之间sCr、cCr、eGFR和尿香草扁桃酸-1水平的变化。
CDDP给药后，随着时间的推移，sCr逐渐升高，eGFR逐渐降低，两组之间的差异在第4天变得显著。然而，尿香草扁桃酸-1水平在CDDP给药后第3天升高，两组之间的差异在第3天显著。第3天尿香草扁桃酸-1的受试者工作特征曲线显示，尿香草扁桃酸-1/尿肌酐为3.17ng时的曲线下面积、敏感性和特异性分别为0.83（P＜0.05）、75.0%和22.7%。尿香草扁桃酸-1低于3.17ng/mg尿肌酐临界值时的非AKI发生率为89.5%。
尿香草扁桃酸-1是用于早期预测CDDP诱导的AKI的一种出色的微创生物标志物。
