Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Neonatal Intensive Care Unit, IRCCS S. Orsola-Malpighi Hospital, Bologna, Italy.
Pediatr Res. 2022 Jun;91(7):1715-1722. doi: 10.1038/s41390-021-01905-9. Epub 2021 Dec 11.
Following preterm birth, the immature kidney is exposed to several harmful conditions, with an increased risk of renal impairment. We aimed to assess urinary biomarkers of renal function in very preterm infants during early nephrotoxic treatments.
Infants ≤32 weeks' gestation and ≤1500 g were enrolled in this observational prospective study. Urine samples were collected on day 1(T1), 2-4(T2), 5-7(T3), 8-10(T4), 11-13(T5). The following urinary biomarkers were determined: osteopontin (uOPN), epidermal growth factor (uEGF), neutrophil gelatinase-associated lipocalin (uNGAL), cystatin C (uCysC). The infants were grouped according to their exposure to amikacin or ibuprofen during the study period and a between-group comparison of urinary biomarkers at each time point was performed.
Thirty-six infants were included. Urinary CysC, uOPN, and uNGAL rose significantly during ibuprofen or amikacin treatment, while no difference was observed for uEGF. After adjustment for possible influencing factors, amikacin administration was associated with higher uCysC at T1 (p = 0.007) and T2 (p = 0.016), whereas ibuprofen increased uOPN (p = 0.001) and uNGAL concentration (p = 0.009) at T3.
Nephrotoxic therapies induce molecule-specific change patterns of renal function biomarkers in treated preterm infants. Serial assessments of these biomarkers may aid to identify neonates at risk of renal impairment and to develop tailored therapeutic approaches.
Despite the wide use of nephrotoxic therapies in neonatal settings, little is known on their effect on renal function biomarkers in preterm infants. This study describes molecule-specific change patterns of urinary biomarkers during ibuprofen and amikacin administration, suggesting underlying pathophysiological effects on renal function. Given their low analytical costs and non-invasive collection, the urinary biomarkers investigated in this study represent a promising strategy for serial monitoring of renal function in at-risk neonates and may aid the early detection of renal function impairment at different kidney levels during nephrotoxic treatments.
早产儿出生后，其未成熟的肾脏会暴露于多种有害环境中，从而增加肾功能受损的风险。我们旨在评估极早产儿在早期肾毒性治疗期间的肾功能的尿液生物标志物。
本观察性前瞻性研究纳入了胎龄≤32 周且出生体重≤1500g 的婴儿。在第 1 天（T1）、第 2-4 天（T2）、第 5-7 天（T3）、第 8-10 天（T4）、第 11-13 天（T5）收集尿液样本。测定尿骨桥蛋白（uOPN）、表皮生长因子（uEGF）、中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）、胱抑素 C（uCysC）等尿生物标志物。根据研究期间是否接触氨基糖苷类抗生素（阿米卡星）或非甾体类抗炎药（布洛芬），将婴儿分为两组，并对每组各时间点的尿生物标志物进行比较。
36 名婴儿入组。在接受氨基糖苷类抗生素或布洛芬治疗期间，尿 CysC、uOPN 和 uNGAL 水平显著升高，而 uEGF 无差异。在调整了可能的影响因素后，氨基糖苷类抗生素的使用与 T1（p=0.007）和 T2（p=0.016）时 uCysC 升高相关，而布洛芬可增加 T3 时 uOPN（p=0.001）和 uNGAL 浓度（p=0.009）。
肾毒性治疗会引起治疗早产儿尿液生物标志物的特定功能变化模式。对这些生物标志物的连续评估可能有助于识别有肾功能损害风险的新生儿，并制定个体化的治疗方法。
尽管氨基糖苷类抗生素和非甾体类抗炎药在新生儿中广泛应用，但关于其对早产儿肾功能生物标志物的影响知之甚少。本研究描述了布洛芬和氨基糖苷类抗生素治疗期间尿液生物标志物的特定功能变化模式，提示其对肾功能具有潜在的病理生理作用。鉴于其分析成本低且采集方便，本研究中所研究的尿液生物标志物代表了一种有前途的策略，可用于监测高危新生儿的肾功能，并且可能有助于在肾毒性治疗期间在不同肾脏水平上早期发现肾功能损害。
