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尿生物标志物作为预后工具的应用:预测儿童急性肾损伤的肾脏转归

The use of urinary biomarkers as prognostic tools: predicting kidney outcomes in pediatric acute kidney injury.

作者信息

Hui Wun Fung, Chan Renee Wan Yi, Tang Man Fung, Lei Tony Chun Hei, Liu Tsz Ki, Ho Kwok Hei, Ku Shu Wing, Leung Ting Fan, Hon Kam Lun

机构信息

Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, 9/F, Tower B, 1 Shing Cheong Road, Kowloon Bay, Kowloon, Hong Kong.

Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

出版信息

Pediatr Nephrol. 2025 Aug 13. doi: 10.1007/s00467-025-06920-0.

Abstract

BACKGROUND

There is limited data on applying urinary biomarkers for prediction of kidney outcomes in pediatric acute kidney injury (AKI).

METHODS

We prospectively measured urinary neutrophil gelatinase-associated lipocalin (NGAL), tissue metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP-7) and C-C motif chemokine ligand 14 (CCL14), alongside serum kidney function test in critically ill children with AKI admitted to the pediatric intensive care unit. The primary outcomes included persistent AKI (lasting for ≥ 72 h) and prolonged AKI (lasting for ≥ 7 days).

RESULTS

There were altogether 134 patients (median age 4.3 years; 43.3% female; AKI severity stage 1: 44.8%, stage 2: 33.6% and stage 3: 21.6%). The incidence of persistent and prolonged AKI was 40.3% and 25.4%, respectively. All four biomarkers, either measured singly, simultaneously or serially, significantly predicted both outcomes, with NGAL demonstrating the best performance (areas under the curve [AUC] 0.72 [0.61, 0.83] for persistent AKI and 0.72 [0.61, 0.84] for prolonged AKI). Integrating the simultaneous AKI staging with biomarker levels significantly improved prediction (NGAL: AUC 0.86 [0.78, 0.94] for persistent AKI and 0.87 [0.79, 0.96] for prolonged AKI). Persistent AKI increased the risk of acute kidney disease (hazard ratios [HR]: 2.59 [1.55, 4.34]), which was associated with kidney function non-recovery 90 days after AKI (HR 7.73 [1.01, 59.03]).

CONCLUSIONS

Urinary NGAL, TIMP-2, IGFBP-7 and CCL14 demonstrated promising performance of predicting kidney function non-recovery within 7 days of AKI onset. Integrating urinary biomarkers with concurrent clinical data substantially enhanced predictive performance.

摘要

背景

关于应用尿液生物标志物预测儿童急性肾损伤(AKI)肾脏预后的数据有限。

方法

我们对入住儿科重症监护病房的危重症AKI患儿前瞻性地检测了尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、组织金属蛋白酶-2(TIMP-2)、胰岛素样生长因子结合蛋白7(IGFBP-7)和C-C基序趋化因子配体14(CCL14),同时进行了血清肾功能检测。主要结局包括持续性AKI(持续≥72小时)和迁延性AKI(持续≥7天)。

结果

共有134例患者(中位年龄4.3岁;43.3%为女性;AKI严重程度1期:44.8%,2期:33.6%,3期:21.6%)。持续性和迁延性AKI的发生率分别为40.3%和25.4%。所有四种生物标志物,无论是单独、同时或连续检测,均能显著预测这两种结局,其中NGAL表现最佳(持续性AKI的曲线下面积[AUC]为0.72[0.61, 0.83],迁延性AKI的AUC为0.72[0.61, 0.84])。将同时期的AKI分期与生物标志物水平相结合可显著提高预测能力(NGAL:持续性AKI的AUC为0.86[0.78, 0.94],迁延性AKI的AUC为0.87[0.79, 0.96])。持续性AKI增加了急性肾病的风险(风险比[HR]:2.59[1.55, 4.34]),这与AKI后90天肾功能未恢复相关(HR 7.73[1.01, 59.03])。

结论

尿NGAL、TIMP-2、IGFBP-7和CCL14在预测AKI发病7天内肾功能未恢复方面表现出良好的性能。将尿液生物标志物与同期临床数据相结合可显著提高预测性能。

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