Background

Characterizing the dynamics of serum creatinine concentrations (Scr) and associated creatinine clearance (CLcr) as a measure of kidney function in extremely low birth weight (≤ 1000 g; ELBW) neonates remains challenging.

Methods

We performed a retrospective study that included longitudinal Scr (enzymatic assay) data from 148 ELBW neonates up to 6 weeks after birth. Change of Scr and inter-individual variability was characterized with nonlinear mixed-effect modeling. Key covariates such as gestational age (GA), mode of delivery (MOD), and treatment with ibuprofen or inotropic agents were investigated.

Results

A total of 2814 Scr concentrations were analyzed. GA was associated with Scr at birth (higher with advancing GA), and GA and MOD showed an association with postnatal maturation of CLcr (faster clearance increase with advancing GA and after C-section). Small CLcr decrease (≤ 5%) was quantified during ibuprofen treatment. For a GA of 27 weeks, mean Scr (estimated CLcr) at birth was 0.61 mg/dl (0.23 ml/min), increasing to 0.87 mg/dl (0.27 ml/min) at day three, and decreasing to 0.36 mg/dl (0.67 ml/min) at day 42 after birth.

Conclusions

We report the first mathematical model able to characterize Scr and CLcr in ELBW neonates during the first 6 weeks of life in a quantitative manner as a function of GA, MOD, and ibuprofen treatment. This model allows the derivation of GA-adjusted reference ranges for ELBW neonates and provides a rationale for normative Scr concentrations, and as such will help clinicians to further optimize monitoring and treatment decisions in this vulnerable patient population.

中文翻译：

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在生命的前 6 周内表征极低出生体重新生儿的血清肌酐和肌酐清除率动态。

背景

将血清肌酐浓度 (Scr) 和相关肌酐清除率 (CLcr) 的动态表征为极低出生体重 (≤ 1000 g; ELBW) 新生儿的肾功能指标仍然具有挑战性。

方法

我们进行了一项回顾性研究，其中包括来自 148 名 ELBW 新生儿直至出生后 6 周的纵向 Scr（酶分析）数据。用非线性混合效应模型表征 Scr 的变化和个体间变异性。研究了关键协变量，例如胎龄 (GA)、分娩方式 (MOD) 和布洛芬或正性肌力药物的治疗。

结果

总共分析了 2814 种 Scr 浓度。GA 与出生时的 Scr 相关（随着 GA 的推进而更高），并且 GA 和 MOD 显示出与 CLcr 的出生后成熟相关（随着 GA 的推进和剖腹产后清除率增加更快）。在布洛芬治疗期间量化了小的 CLcr 下降（≤ 5%）。对于 27 周的 GA，出生时的平均 Scr（估计 CLcr）为 0.61 mg/dl（0.23 ml/min），在第三天增加到 0.87 mg/dl（0.27 ml/min），然后下降到 0.36 mg/dl (0.67 毫升/分钟) 在出生后第 42 天。

结论

我们报告了第一个能够在生命的前 6 周内以定量方式表征 ELBW 新生儿的 Scr 和 CLcr 的数学模型，作为 GA、MOD 和布洛芬治疗的函数。该模型允许推导出 ELBW 新生儿的 GA 调整参考范围，并为规范的 Scr 浓度提供基本原理，因此将帮助临床医生进一步优化对这一易感患者群体的监测和治疗决策。