Time-dependent changes in kidney injury biomarkers in patients receiving multiple cycles of cisplatin chemotherapy
Time-dependent changes in kidney injury biomarkers in patients receiving multiple cycles of cisplatin chemotherapy
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DOI：
10.1016/j.toxrep.2020.04.003
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发表时间：
2020-01-01
影响因子：
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通讯作者：
Aleksunes, Lauren M.
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文献类型：
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作者：
George, Blessy;Wen, Xia;Aleksunes, Lauren M.
肾小管损伤后分泌到尿液中的蛋白质越来越多地被用作临床和亚临床肾毒性的生物标志物。在本研究中，我们试图描述27例实体瘤患者在两个不同的化疗周期中，三种有希望的生物标志物肾损伤分子-1（KIM-1）、钙结合蛋白和三叶因子3（TFF 3）的尿排泄的时间依赖性，这些患者接受了抗癌药物顺铂（>= 25 mg/m2）。在顺铂化疗的初始和后续周期期间，在第3天和第10天评价尿生物标志物。纵向分析比较了顺铂治疗初始和后续周期期间和期间生物标志物浓度的平均差异估计值。传统的生物标志物包括血清肌酐、估计的肾小球滤过率和血尿素氮在顺铂治疗的两个周期内和整个周期内均无变化。作为对初始周期的响应，尿KIM-1浓度从基线增加，并在随后的顺铂化疗周期中保持升高。相比之下，初始顺铂治疗后10天尿钙结合蛋白水平升高，但在随后的周期中顺铂暴露基本不变。在顺铂治疗的初始和后续周期中，均观察到顺铂给药后3天尿TFF 3的早期升高。总之，在同一肿瘤患者队列中生物标志物性能的纵向评估揭示了含顺铂化疗的初始和后续周期之间的不同尿排泄模式。这些数据增加了新的周期依赖性的见解，越来越多的文献解决尿生物标志物的能力，以检测接受顺铂的患者亚临床肾损伤。
Proteins secreted into urine following tubular injury are being increasingly used as biomarkers of clinical and subclinical nephrotoxicity. In the present study, we sought to characterize the time-dependent urinary excretion of three promising biomarkers, kidney injury molecule-1 (KIM-1), calbindin, and trefoil factor 3 (TFF3), during two different chemotherapy cycles in 27 patients with solid tumors prescribed the anticancer drug cisplatin (>= 25 mg/m(2)). Urinary biomarkers were evaluated at Days 3 and 10 during an initial and a subsequent cycle of cisplatin chemotherapy. Longitudinal analyses compared the mean difference estimations for biomarker concentrations during and across the initial and subsequent cycles of cisplatin treatment. Traditional biomarkers including serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen were unchanged during and across both cycles of cisplatin therapy. In response to the initial cycle, urinary KIM-1 concentrations increased from baseline and remained elevated through a subsequent cycle of cisplatin chemotherapy. By comparison, urinary levels of calbindin were elevated 10 days after the initial cisplatin treatment, but largely unchanged by cisplatin exposure in a subsequent cycle. Early elevations in urinary TFF3 at 3 days after cisplatin administration were observed consistently in both the initial and subsequent cycle of cisplatin treatment. In conclusion, the longitudinal assessment of biomarker performance in the same cohort of oncology patients reveals different patterns of urinary excretion between initial and subsequent cycles of cisplatin-containing chemotherapy. These data add novel cycle-dependent insight to the growing literature addressing the ability of urinary biomarkers to detect subclinical renal injury in patients receiving cisplatin.