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尿足细胞蛋白作为肾小球成熟和损伤的生物标志物,与危重新生儿急性肾损伤和死亡相关。

Urinary Nephrin as a Biomarker of Glomerular Maturation and Injury Is Associated with Acute Kidney Injury and Mortality in Critically Ill Neonates.

机构信息

Pediatric Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, China.

Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.

出版信息

Neonatology. 2019;116(1):58-66. doi: 10.1159/000499083. Epub 2019 Apr 12.

DOI:10.1159/000499083
PMID:30982033
Abstract

BACKGROUND

Nephrin is a key component of the slit diaphragm of the glomerular podocyte, and increased urinary nephrin level may reflect glomerular injury.

OBJECTIVES

To determine whether urinary nephrin is a useful biomarker of glomerular maturation and injury and whether it is associated with acute kidney injury (AKI) and neonatal intensive care unit (NICU) mortality in critically ill neonates.

METHODS

Urinary samples were serially collected in 234 neonates during NICU stay for measurements of nephrin, cystatin C (CysC), and albumin. AKI diagnosis was based on neonatal Kidney Disease: Improving Global Outcome (KDIGO) criteria.

RESULTS

Of the neonates, 26 developed AKI and 24 died during NICU stay. The independent contributors to the initial urinary nephrin level obtained on the first 24 h admitted to NICU were gestational age (p = 0.004) and initial urinary CysC level (p < 0.001). Both initial (p = 0.037) and peak (p = 0.039) urinary nephrin were significantly associated with AKI, even after controlling for significant covariates, and had an area under the receiver-operating characteristic curve (AUC) of 0.71 and 0.70, respectively, for predicting AKI. At the optimal cutoff value of 0.375 μg/mg urinary creatinine, the initial urinary nephrin displayed sensitivity of 61.5% and specificity of 76.9% for predicting AKI. The AUCs for initial and peak urinary nephrin to predict NICU mortality were 0.81 and 0.83, respectively.

CONCLUSIONS

Urinary nephrin, which may decrease with increasing glomerular maturity, is significantly associated with increased risk for AKI and NICU mortality even after adjustment for potential confounders. A higher level of urinary nephrin may be independently predictive of AKI and NICU mortality in critically ill neonates.

摘要

背景

足细胞裂孔隔膜的关键组成部分是 Nephrin,尿 Nephrin 水平升高可能反映肾小球损伤。

目的

确定尿 Nephrin 是否是肾小球成熟和损伤的有用生物标志物,以及它是否与危重新生儿急性肾损伤 (AKI) 和新生儿重症监护病房 (NICU) 死亡率相关。

方法

在 NICU 住院期间,对 234 名新生儿连续采集尿样,用于测量 Nephrin、胱抑素 C (CysC) 和白蛋白。AKI 诊断基于新生儿肾脏病:改善全球结局 (KDIGO) 标准。

结果

在这些新生儿中,有 26 名发生 AKI,有 24 名在 NICU 期间死亡。首次入住 NICU 后 24 小时内尿 Nephrin 初始水平的独立贡献因素为胎龄 (p = 0.004) 和初始尿 CysC 水平 (p < 0.001)。 初始 (p = 0.037) 和峰值 (p = 0.039) 尿 Nephrin 与 AKI 显著相关,即使在控制了重要的协变量后,其预测 AKI 的受试者工作特征曲线 (ROC) 下面积 (AUC) 分别为 0.71 和 0.70。在最佳截断值 0.375μg/mg 尿肌酐时,初始尿 Nephrin 对预测 AKI 的灵敏度为 61.5%,特异性为 76.9%。初始和峰值尿 Nephrin 预测 NICU 死亡率的 AUC 分别为 0.81 和 0.83。

结论

尿 Nephrin 可能随着肾小球成熟而降低,即使在调整了潜在混杂因素后,与 AKI 和 NICU 死亡率的风险增加显著相关。较高水平的尿 Nephrin 可能是危重新生儿 AKI 和 NICU 死亡率的独立预测因素。

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