Background

Acute kidney injury (AKI) is common and is associated with poor clinical outcomes in premature neonates. Urine biomarkers hold the promise to improve our understanding and care of patients with kidney disease. Because kidney maturation and gender can impact urine biomarker values in extremely low gestational age neonates (ELGANs), careful control of gestational age (GA) and time is critical to any urine biomarker studies in neonates.

Methods

To improve our understanding of the potential use of urine biomarkers to detect AKI during the first postnatal weeks, we performed a nested case–control study to evaluate 21 candidate urine AKI biomarkers. Cases include 20 ELGANs with severe AKI. Each case was matched with 2 controls for the same GA week (rounded down to the nearest week), gender, and birth weight (BW) (± 50 g).

Results

Urine cystatin C, creatinine, ghrelin, fibroblast growth factor-23 (FGF23), tissue metalloproteinase 2 (TIMP2) and vascular endothelial growth factor A (VEGFa) concentrations were higher in ELGANs with early severe AKI compared to matched control subjects without AKI. Urine epidermal growth factor (EGF) and uromodulin (UMOD) concentrations are lower in cases than controls. Interleukin (IL)-15 was lower on day 1, but higher on day 8 in cases than controls; while VEGFa was lower on day 1, but higher on day 5 in cases than controls.

Conclusion

Urine biomarkers hold the promise to improve our ability to reliably detect kidney injury. Interventional studies are needed to determine the biomarkers’ ability to predict outcomes, enhance AKI phenotypes, and improve timely interventions which can prevent the sequalae of AKI in ELGANs.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information

中文翻译：

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极低胎龄新生儿尿液急性肾损伤生物标志物：21 种候选尿液生物标志物的巢式病例对照研究

背景

急性肾损伤 (AKI) 很常见，并且与早产儿临床结局不佳相关。尿液生物标志物有望提高我们对肾脏疾病患者的了解和护理。由于肾脏成熟度和性别会影响极低胎龄新生儿 (ELGAN) 的尿液生物标志物值，因此仔细控制胎龄 (GA) 和时间对于新生儿尿液生物标志物研究至关重要。

方法

为了加深我们对尿液生物标志物在产后最初几周检测 AKI 的潜在用途的了解，我们进行了一项巢式病例对照研究，以评估 21 种候选尿液 AKI 生物标志物。病例包括 20 名患有严重 AKI 的 ELGAN。每个病例均与同一 GA 周（四舍五入至最近的周）、性别和出生体重 (BW) (± 50 g) 的 2 个对照进行匹配。

结果

与没有 AKI 的匹配对照受试者相比，患有早期严重 AKI 的 ELGAN 受试者的尿液胱抑素 C、肌酐、生长素释放肽、成纤维细胞生长因子 23 (FGF23)、组织金属蛋白酶 2 (TIMP2) 和血管内皮生长因子 A (VEGFa) 浓度较高。病例中尿液表皮生长因子（EGF）和尿调节素（UMOD）浓度低于对照组。病例中白细胞介素 (IL)-15 在第 1 天低于对照组，但在第 8 天高于对照组；与对照组相比，病例中 VEGFa 在第 1 天较低，但在第 5 天较高。

结论

尿液生物标志物有望提高我们可靠检测肾损伤的能力。需要进行干预性研究来确定生物标志物预测结果的能力，增强 AKI 表型，并改进及时干预措施，以预防 ELGAN 中 AKI 的后遗症。

图形概要

更高分辨率版本的图形摘要可作为补充信息提供