Division of Nephrology, Department of Pediatrics, Research Institute of the McGill University Health Centre, McGill University Health Centre, Montreal Children's Hospital, Montreal, Quebec, Canada.
Division of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Kidney360. 2021 Nov 3;3(1):37-50. doi: 10.34067/KID.0004802021. eCollection 2022 Jan 27.
Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin.
Participants (=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured () pre-cisplatin infusion, () post-infusion (morning after), and () at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher).
Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; <0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65).
Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.
鲜有研究描述了顺铂治疗儿童急性肾损伤（AKI）生物标志物尿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）与 AKI 之间的关系。我们旨在描述顺铂治疗儿童的尿液 NGAL 和 KIM-1 的排泄模式及其与 AKI 的关系。
2013 年至 2017 年，我们在加拿大 12 家儿科医院进行了一项前瞻性队列研究，共纳入了 159 名参与者。在早期（第 1 或第 2 个顺铂周期）和顺铂晚期（最后或倒数第 2 个周期）顺铂输注时评估参与者。在顺铂输注前（）、输注后（清晨）和（）以及早期和顺铂输注时的住院期间（）测量尿液 NGAL 和 KIM-1。主要结局：根据肾脏疾病改善全球结果指南标准（第 1 期或更高），定义为顺铂给药后 10 天内血清肌酐升高的 AKI。
在 159 名儿童中，156 名（中位数[四分位距（IQR）]年龄：5.8[2.4-12.0]岁；78[50%]女性）在早期顺铂输注时具有生物标志物数据，127 名在晚期顺铂输注时有数据。在早期和晚期顺铂输注后 10 天内，分别有 46 名（29%）和 22 名（17%）儿童发生 AKI。与无 AKI 相比，AKI 患者的尿液 NGAL 和 KIM-1 浓度显著升高（晚期顺铂输注接近出院时，中位数[IQR]NGAL 水平分别为 76.1[10.0-232.7]ng/mg 肌酐；KIM-1 水平分别为 4415[2083-9077]pg/mg 肌酐；<0.01）。这些标志物对 AKI 有一定的鉴别能力（受试者工作特征曲线下面积[AUC-ROC]范围：NGAL，0.56-0.72；KIM-1，0.48-0.75）。与早期顺铂输注（AUC-ROC 范围，0.48-0.65）相比，晚期顺铂输注时标志物浓度更高，对 AKI 的鉴别能力更强（AUC-ROC 范围，0.54-0.75）。
尿液 NGAL 和 KIM-1 对顺铂相关性 AKI 的鉴别能力有限。需要进一步研究以确定这些标志物的临床实用性和适用性及其与晚期肾脏结局的关系。
