Early prediction of cisplatin nephrotoxicity in head and neck cancer patients – An evaluation with urinary biomarkers

S. Ummer, K. Nalini, K. Gopalakrishna, R. Prabhu, Athiyamaan, A. Kamath, Vidyasagar
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Abstract

Background: Nephrotoxic Acute Kidney Injury (AKI) is a common condition associated with considerable morbidity and mortality. Acute exposure to potentially nephrotoxic drugs requires early appraisal of the extent of renal injury to determine the need for specific interventions. Hence this study was designed to evaluate two urinary biomarkers for the early diagnosis of AKI due to cisplatin chemotherapy, including Neutrophil gelatinase-associated lipocalin (uNGAL) and Cystatin C (uCysC). Methods: Urinary biomarker levels in cisplatin treated cancer patients were estimated before and at 2hrs, 6hrs, 12hrs, 24hrs and 48hrs after cisplatin administration. Diagnostic performances of biomarkers were studied by ROC analysis with AUC and predictive values. Results: uNGAL was identified as the earlier biomarker of AKI induced by cisplatin as it detected kidney injury as early as 2hrs after the exposure of nephrotoxic drug with an AUC of 0.8, which is 46hrs before the elevation of serum creatinine. uCysC detected AKI 6hrs after cisplatin administration with AUC 0.73. Conclusion: Indication of AKI by biomarker elevations can provide an early warning signal which may have implications in therapy by either stopping the nephrotoxic drug or reducing its dose or even by substituting it with a less nephrotoxic one. The research in this direction should focus on evolving rapid procedures with an eventual point-of-care test for urinary biomarker determinations that will transform the scope of biomarkers significantly in the field of early renal injury.
头颈癌患者顺铂肾毒性的早期预测——尿液生物标志物的评估
背景:肾毒性急性肾损伤(AKI)是一种常见的疾病,具有相当高的发病率和死亡率。急性暴露于潜在的肾毒性药物需要早期评估肾脏损伤的程度,以确定是否需要特殊的干预措施。因此,本研究旨在评估两种用于顺铂化疗引起AKI早期诊断的尿液生物标志物,包括中性粒细胞明胶酶相关脂钙蛋白(uNGAL)和胱抑素C (uCysC)。方法:评估顺铂治疗癌症患者在给药前、给药后2小时、6小时、12小时、24小时和48小时的尿液生物标志物水平。通过ROC分析、AUC和预测值研究生物标志物的诊断性能。结果:uNGAL是顺铂所致AKI的较早生物标志物,其在肾毒性药物暴露后2小时检测到肾损伤,AUC为0.8,比血清肌酐升高早46小时。顺铂给药后6小时uCysC检测AKI, AUC为0.73。结论:通过生物标志物升高的适应症可以提供早期预警信号,这可能对治疗有影响,可以停止肾毒性药物或减少其剂量,甚至用肾毒性较小的药物替代。这个方向的研究应该集中在发展快速的程序,最终实现尿液生物标志物测定的即时检测,这将显著改变早期肾损伤领域生物标志物的范围。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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