Predictors of augmented renal clearance based on iohexol plasma clearance in critically ill children

Background 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 iohexol ) to measure glomerular filtration rate (GFR). Methods This is a retrospective analysis of data from the “IOHEXOL” study which validated GFR estimating formulas (eGFR) against CL iohexol . Critically ill children with normal serum creatinine were included, and CL iohexol was performed as soon as possible after pediatric intensive care unit (PICU) admission (CL iohexol1 ) and repeated (CL iohexol2 ) after 48–72 h whenever possible. ARC was defined as CL iohexol exceeding normal GFR for age plus two standard deviations. Results Eighty-five patients were included; 57% were postoperative patients. Median CL iohexol1 was 122 mL/min/1.73 m 2 (IQR 75–152). Forty patients (47%) expressed ARC on CL iohexol1 . 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 2 and 140 mL/min/1.73 m 2 was suggested to identify ARC in children under and above 2 years, respectively. ARC showed a tendency to persist on CL iohexol2 . Conclusions 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. Trial registration ClinicalTrials.gov NCT05179564, registered retrospectively on January 5, 2022. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information