Mercier Kelly, McRitchie Susan, Pathmasiri Wimal, Novokhatny Andrew, Koralkar Rajesh, Askenazi David, Brophy Patrick D, Sumner Susan
RTI International, 3040 E. Cornwallis Road, Research Triangle Park, Triangle, NC, 27709, USA.
University of Alabama Children's Hospital, Birmingham, AL, USA.
Pediatr Nephrol. 2017 Jan;32(1):151-161. doi: 10.1007/s00467-016-3439-9. Epub 2016 Jul 19.
Acute kidney injury (AKI) staging has been developed in the adult and pediatric populations, but these do not yet exist for the neonatal population. Metabolomics was utilized to uncover biomarkers of normal and AKI-associated renal function in preterm infants. The study comprised 20 preterm infants with an AKI diagnosis who were matched by gestational age and gender to 20 infants without an AKI diagnosis.
Urine samples from pre-term newborn infants collected on day 2 of life were analyzed using broad-spectrum nuclear magnetic resonance (NMR) metabolomics. Multivariate analysis methods were used to identify metabolite profiles that differentiated AKI and no AKI, and to identify a metabolomics profile correlating with gestational age in infants with and without AKI.
There was a clear distinction between the AKI and no-AKI profiles. Two previously identified biomarkers of AKI, hippurate and homovanillate, differentiated AKI from no-AKI profiles. Pathway analysis revealed similarities to cholinergic neurons, prenatal nicotine exposure on pancreatic β cells, and amitraz-induced inhibition of insulin secretion. Additionally, a pH difference was noted. Both pH and the metabolites were found to be associated with AKI; however, only the metabotype was a significant predictor of AKI. Pathways for the no-AKI group that correlated uniquely with gestational age included aminoacyl-t-RNA biosynthesis, whereas pathways in the AKI group yielded potential metabolite changes in pyruvate metabolism.
Metabolomics was able to differentiate the urinary profiles of neonates with and without an AKI diagnosis and metabolic developmental profiles correlated with gestational age. Further studies in larger cohorts are needed to validate these results.
急性肾损伤（AKI）分期已在成人和儿科人群中得到发展，但新生儿人群中尚未有此类分期。代谢组学被用于揭示早产儿正常和与AKI相关的肾功能生物标志物。该研究包括20名被诊断为AKI的早产儿，这些早产儿在胎龄和性别上与20名未被诊断为AKI的婴儿相匹配。
使用广谱核磁共振（NMR）代谢组学分析出生后第2天收集的早产新生儿尿液样本。采用多变量分析方法来识别区分AKI和非AKI的代谢物谱，并识别与有或无AKI的婴儿胎龄相关的代谢组学谱。
AKI和非AKI谱之间有明显区别。两种先前确定的AKI生物标志物，马尿酸盐和高香草酸，可区分AKI和非AKI谱。通路分析显示与胆碱能神经元、产前尼古丁暴露对胰腺β细胞的影响以及双甲脒诱导的胰岛素分泌抑制存在相似之处。此外，还注意到了pH差异。pH和代谢物均与AKI相关；然而，只有代谢型是AKI的显著预测指标。与胎龄唯一相关的非AKI组通路包括氨酰-t-RNA生物合成，而AKI组通路在丙酮酸代谢中产生了潜在的代谢物变化。
代谢组学能够区分有和没有AKI诊断的新生儿尿液谱以及与胎龄相关的代谢发育谱。需要在更大的队列中进行进一步研究以验证这些结果。
