Renal Function Assessment in Critically Ill Children (IOHEXOL)

Identification of renal dysfunction in critically ill children is often delayed due to lack of accurate methods for evaluation of glomerular filtration rate (GFR). The investigators compared GFR measurement by the gold standard technique iohexol plasma clearance with estimated GFR (eGFR) based on selected established formulas incorporating the renal biomarkers creatinine, cystatin C and betatrace protein.

Acute kidney injury (AKI) is a frequent comorbidity of critical illness associated with poor outcome, including prolonged duration of mechanical ventilation, longer length of stay and increased mortality or progression to chronic kidney disease on the long term. The reported incidence of AKI in critically ill children and neonates varies widely between 10% and 80% depending on the diagnostic criteria. Besides a decline in renal function, also the phenomenon of augmented renal clearance (ARC) and in consequence enhanced clearance of renally eliminated drugs, is increasingly recognized in pediatric intensive care patients. Hence, accurate assessment of renal function is crucial in the intensive care population to guide therapy. But to date consensus is lacking about the reliability of common GFR estimation methods based on the endogenous renal biomarkers serum creatinine, cystatin C and betatrace protein in critical care patients. the aim of this study is to measure GFR in a reliable way by iohexol plasma clearance and evaluate the agreement between the gold standard technique iohexol plasma clearance and biomarker-based formula to estimate GFR.

Iohexol, Pharmacokinetics, Renal Function, Critically Ill Children, Acute Kidney Injury, Augmented Renal Clearance

a weight-dependent dose of iohexol will be injected as an intravenous bolus in 100 patients 2,5 -9kg = 1ml; 10-19kg = 2ml; 20-29kg = 3ml; 30-39kg = 4ml; ≥ 40kg = 5ml

Blood sampling will be performed through an arterial (preferred) or venous line, other than the iohexol infusion line. In the first 30 minutes after iohexol injection, a blood sample of 2 ml will be obtained for iohexol concentration measurement and determination of renal biomarkers serum creatinine, cystatin C, betatrace protein. Subsequently, 2 up to 5 additional blood samples of 0,5 ml will be obtained for iohexol determination at 60,120 ,180, 240 and 360 minutes after iohexol injection to calculate iohexol plasma clearance from the plasma disappearance curve

Agreement between determination of GFR when based on biomarker formulas to estimate GFR compared to measurement of GFR by iohexol plasma clearance

GFR will be calculated by using 26 established mathematical equations based on renal biomarkers Iohexol clearance will be calculated from the plasma iohexol disappearance curve based on 3 up to 6 blood samples drawn for iohexol concentration measurement over a 360 minutes interval after iohexol injection, Clearance = iohexol dose /area under the curve Agreement between reference method iohexol clearance and estimating GFR formulas will be evaluated by Bland -Altman analysis with determination of bias (= iohexol clearance - estimated GFR), precision (=standard deviation of bias), limits of agreement (= bias +- 1.96 x standard deviation) and visual display of Bland-Altman plots for every eGFR formula

Identify which GFR estimating formulas yield a sufficient accuracy to predict GFR in critically ill children

P30 value expresses the percentage of estimated GFR results with evaluated formulas that lie within a 30% range of GFR values measured by iohexol clearance. This P30 value reflects accuracy of a specific GFR estimating formula. Formulas with P30 > 75% have acceptable accuracy to be relied on for GFR determination in clinical practice

Prevalence of Acute Kidney Injury and Augmented Renal Clearance based on iohexol clearance in critically ill children

AKI will be defined by pediatricRIFLE criteria for GFR decline, using age-specific reference values of GFR pRIFLE classification of AKI: Risk = GFR decline > 25% Injury= GFR decline > 50% Failure= GFR decline > 75% ARC will be described as GFR exceeding age-specific reference GFR +2 standard deviations

Inclusion criteria: patients admitted to the pediatric or neonatal intensive care unit 0 - 15 years for neonates: gestational age ≥ 37 weeks bodyweight >2.5kg intra-arterial and/or intravenous access available for iohexol administration and blood sampling Exclusion criteria: no vascular access in place for iohexol administration and blood sampling absence of parental/patient consent known hypersensitivity to contrast media or previous history of adverse reaction after administration of contrast agents known thyroid dysfunction, or for newborns: mother with known thyroid dysfunction extracorporeal circuit (haemodialysis, extra corporal membrane oxygenation (ECMO), peritoneal dialysis) patients with chronic kidney disease or congenital kidney anomalies preterm neonates (gestational age < 37 weeks) body weight < 2.5 kg dehydrated newborns (i.e. loss of birth weight ≥ 10%) planned/expected surgery with extracorporeal circulation within 5 days after inclusion

Dhont E, Windels C, Snauwaert E, Van Der Heggen T, de Jaeger A, Dhondt L, Delanghe J, Croubels S, Walle JV, De Paepe P, De Cock PA. Reliability of glomerular filtration rate estimating formulas compared to iohexol plasma clearance in critically ill children. Eur J Pediatr. 2022 Nov;181(11):3851-3866. doi: 10.1007/s00431-022-04570-0. Epub 2022 Sep 2.