Dhont Evelyn, Van Der Heggen Tatjana, Snauwaert Evelien, Willems Jef, Croubels Siska, Delanghe Joris, De Waele Jan J, Colman Roos, Vande Walle Johan, De Paepe Peter, De Cock Pieter A
Pediatric Intensive Care Unit, Department of Intensive Care Medicine, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium.
Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Pediatr Nephrol. 2024 May;39(5):1607-1616. doi: 10.1007/s00467-023-06221-4. Epub 2023 Nov 23.
Augmented renal clearance (ARC) holds a risk of subtherapeutic drug concentrations. Knowledge of patient-, disease-, and therapy-related factors associated with ARC would allow predicting which patients would benefit from intensified dosing regimens. This study aimed to identify ARC predictors and to describe ARC time-course in critically ill children, using iohexol plasma clearance (CL) to measure glomerular filtration rate (GFR).
This is a retrospective analysis of data from the "IOHEXOL" study which validated GFR estimating formulas (eGFR) against CL. Critically ill children with normal serum creatinine were included, and CL was performed as soon as possible after pediatric intensive care unit (PICU) admission (CL) and repeated (CL) after 48-72 h whenever possible. ARC was defined as CL exceeding normal GFR for age plus two standard deviations.
Eighty-five patients were included; 57% were postoperative patients. Median CL was 122 mL/min/1.73 m (IQR 75-152). Forty patients (47%) expressed ARC on CL. Major surgery other than cardiac surgery and eGFR were found as independent predictors of ARC. An eGFR cut-off value of 99 mL/min/1.73 m and 140 mL/min/1.73 m was suggested to identify ARC in children under and above 2 years, respectively. ARC showed a tendency to persist on CL.
Our findings raise PICU clinician awareness about increased risk for ARC after major surgery and in patients with eGFR above age-specific thresholds. This knowledge enables identification of patients with an ARC risk profile who would potentially benefit from a dose increase at initiation of treatment to avoid underexposure.
ClinicalTrials.gov NCT05179564, registered retrospectively on January 5, 2022.
肾脏清除率增加（ARC）存在药物浓度低于治疗水平的风险。了解与ARC相关的患者、疾病和治疗相关因素，将有助于预测哪些患者将从强化给药方案中获益。本研究旨在确定ARC的预测因素，并描述危重症儿童的ARC时间进程，采用碘海醇血浆清除率（CL）来测量肾小球滤过率（GFR）。
这是一项对“碘海醇”研究数据的回顾性分析，该研究针对CL验证了GFR估算公式（eGFR）。纳入血清肌酐正常的危重症儿童，在儿科重症监护病房（PICU）入院后尽快进行CL检测（CL1），并尽可能在48 - 72小时后重复检测（CL2）。ARC定义为CL超过同年龄正常GFR加两个标准差。
纳入85例患者；57%为术后患者。CL中位数为122 mL/min/1.73m²（四分位间距75 - 152）。40例患者（47%）在CL检测中表现出ARC。发现除心脏手术外的大手术和eGFR是ARC的独立预测因素。建议分别以99 mL/min/1.73m²和140 mL/min/1.73m²的eGFR临界值来识别2岁以下和2岁以上儿童的ARC。ARC在CL检测中呈现持续存在的趋势。
我们的研究结果提高了PICU临床医生对大手术后和eGFR高于年龄特异性阈值患者发生ARC风险增加的认识。这一认识有助于识别具有ARC风险特征的患者，这些患者可能从治疗开始时增加剂量中获益，以避免药物暴露不足。
ClinicalTrials.gov NCT05179564，于2022年1月5日追溯注册。
