Department of Pediatrics, University of Alabama at Birmingham, 1600 5th Avenue South, Birmingham, AL, 35233, USA.
Department of Biostatistics, University of Washington, Seattle, WA, USA.
Pediatr Nephrol. 2023 Apr;38(4):1329-1342. doi: 10.1007/s00467-022-05688-x. Epub 2022 Aug 1.
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.
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).
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.
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. A higher resolution version of the Graphical abstract is available as Supplementary information.
急性肾损伤（AKI）在早产儿中较为常见，与不良临床结局相关。尿生物标志物有望改善我们对肾脏病患者的认识和护理。由于肾脏成熟度和性别会影响极低出生体重儿（ELGAN）的尿生物标志物值，因此在对新生儿进行任何尿生物标志物研究时，都必须严格控制胎龄（GA）和时间。
为了更好地了解在新生儿出生后第一周内使用尿生物标志物检测 AKI 的可能性，我们进行了一项巢式病例对照研究，以评估 21 种候选尿 AKI 生物标志物。病例包括 20 名患有严重 AKI 的 ELGAN。每个病例都与同一 GA 周（向下取整到最近的一周）、性别和出生体重（BW）（±50g）相匹配的 2 名对照相匹配。
与无 AKI 相匹配的对照组相比，早期严重 AKI 的 ELGAN 尿液胱抑素 C、肌酐、胃饥饿素、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）浓度更高。尿液表皮生长因子（EGF）和尿调蛋白（UMOD）浓度低于病例组。与对照组相比，IL-15 在第 1 天较低，但在第 8 天较高；而 VEGFa 在第 1 天较低，但在第 5 天较高。
尿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以确定这些生物标志物预测结局、增强 AKI 表型以及改善及时干预的能力，从而预防 ELGAN 中 AKI 的后遗症。更详细的图表摘要版本可作为补充信息提供。
