Department of Pediatrics, Division of Nephrology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Division of Nephrology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
J Clin Pharmacol. 2021 Jul;61(7):871-880. doi: 10.1002/jcph.1839. Epub 2021 Apr 15.
Cisplatin is a chemotherapeutic agent highly excreted in urine and known to cause acute kidney injury (AKI). As AKI diagnosis by serum creatinine (SCr) is usually delayed, endeavors for finding early AKI biomarkers continue. This study aims to determine if urine platinum (UP) concentration 24 hours after cisplatin infusion is associated with AKI, and to evaluate the association between urine platinum and tubular damage biomarkers: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Children treated with cisplatin in 12 Canadian centers (April 2013 to December 2017) were included. Urine from the morning after the first cisplatin infusion of the first or second cisplatin cycle was measured for urine platinum, NGAL, and KIM-1. SCr and serum electrolytes were used to detect AKI by either SCr elevation or urinary electrolyte wasting (potassium, magnesium, phosphate). The associations of urine platinum with AKI, NGAL, and KIM-1 were assessed. A total of 115 participants (54% boys, median age, 8.5 years; interquartile range, 4.0-13.4) were included, of which 29 (25%) and 105 (91%) developed AKI defined by SCr and electrolyte criteria, respectively. Higher urine platinum was associated with higher cisplatin dose (Spearman rho, 0.21) and with younger age (Spearman rho, -0.33). Urine platinum was not associated with postinfusion AKIor KIM-1, but was weakly associated with NGAL, particularly in participants without SCr AKI (Pearson's r, 0.22). Urine platinum may be a marker of mild tubular injury but is not likely to be a useful biomarker of clinically evident AKI.
顺铂是一种在尿液中高度排泄的化疗药物,已知会导致急性肾损伤(AKI)。由于血清肌酐(SCr)检测通常会延迟 AKI 的诊断,因此人们仍在努力寻找早期 AKI 的生物标志物。本研究旨在确定顺铂输注后 24 小时尿液中的铂浓度是否与 AKI 相关,并评估尿液铂与肾小管损伤生物标志物:中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和肾损伤分子-1(KIM-1)之间的相关性。本研究纳入了在加拿大 12 个中心接受顺铂治疗的儿童(2013 年 4 月至 2017 年 12 月)。检测第一个或第二个顺铂周期的第一天顺铂输注后清晨的尿液中的尿铂、NGAL 和 KIM-1。使用 SCr 和血清电解质检测 AKI,包括 SCr 升高或尿电解质丢失(钾、镁、磷)。评估了尿铂与 AKI、NGAL 和 KIM-1 的相关性。共纳入 115 名参与者(54%为男孩,中位年龄为 8.5 岁;四分位间距,4.0-13.4),其中 29 名(25%)和 105 名(91%)参与者分别根据 SCr 和电解质标准定义为 AKI。尿铂浓度与顺铂剂量较高(Spearman rho,0.21)和年龄较小(Spearman rho,-0.33)相关。尿铂与输注后 AKI 或 KIM-1 无相关性,但与 NGAL 呈弱相关性,尤其是在无 SCr AKI 的参与者中(Pearson's r,0.22)。尿铂可能是轻度肾小管损伤的标志物,但不太可能是临床明显 AKI 的有用生物标志物。