Profiling of Kidney Injury Biomarkers in Patients Receiving Cisplatin: Time-dependent Changes in the Absence of Clinical Nephrotoxicity.
Profiling of Kidney Injury Biomarkers in Patients Receiving Cisplatin: Time-dependent Changes in the Absence of Clinical Nephrotoxicity.
复制标题
DOI：
10.1002/cpt.606
复制
发表时间：
2017-04
影响因子：
6.7
通讯作者：
Aleksunes LM
中科院分区：
文献类型：
--
作者：
George B;Wen X;Mercke N;Gomez M;O'Bryant C;Bowles DW;Hu Y;Hogan SL;Joy MS;Aleksunes LM
含顺铂方案治疗实体瘤的成功部分受到肾毒性的限制。在啮齿类动物中，几种尿蛋白已成为顺铂诱导肾损伤的更敏感指标。我们试图描述顺铂治疗后12种蛋白质（包括KIM-1、钙结合蛋白、β 2 M和TFF 3）尿浓度的时间依赖性变化。从接受门诊顺铂治疗（≥ 25 mg/m2）的57例实体瘤患者中采集基线、3（范围：2-5）和10（范围：9-11）天的尿液。顺铂输注后血清肌酐基本不变。然而，与基线值相比，尿液中的几种新型生物标志物显著增加，包括β 2 M，其在第3天高3倍（p<0.0001）。到第10天，尿KIM-1和TFF 3升高2倍（分别为p=0.002和p=0.002），而钙结合蛋白水平升高8倍（p<0.0001）。我们报告了顺铂治疗后亚临床肾损伤的非侵入性标志物尿排泄的新的时间依赖性变化。
The success of cisplatin-containing regimens to treat solid tumors is limited, in part, by nephrotoxicity. In rodents, several urinary proteins have emerged as more sensitive indicators of cisplatin-induced kidney injury. We sought to characterize time-dependent changes in the urinary concentrations of 12 proteins including KIM-1, calbindin, β2M, and TFF3 after cisplatin therapy. Urine was collected at baseline, 3 (range: 2-5), and 10 (range: 9-11) days from 57 patients with solid tumors receiving outpatient cisplatin therapy (≥ 25 mg/m2). Serum creatinine was largely unchanged after cisplatin infusion. However, compared to baseline values, several novel biomarkers were significantly increased in the urine including β2M, which was 3-fold higher by day 3 (p<0.0001). Urinary KIM-1 and TFF3 were elevated 2-fold by day 10 (p=0.002 and p=0.002, respectively) whereas calbindin levels were increased 8-fold (p<0.0001). We report novel time-dependent changes in the urinary excretion of noninvasive markers of subclinical kidney injury after cisplatin treatment.