Iohexol plasma clearance in children: validation of multiple formulas and single-point sampling times

Abstract

BackgroundThe non-ionic agent iohexol is increasingly used as the marker of choice for glomerular filtration rate (GFR) measurement. Estimates of GFR in children have low accuracy and limiting the number of blood-draws in this patient population is especially relevant. We have performed a study to evaluate different formulas for calculating measured GFR based on plasma iohexol clearance with blood sampling at only one time point (GFR1p) and to determine the optimal sampling time point.MethodsNinety-six children with chronic kidney disease (CKD) stage 1–5 (median age 9.2 years; range 3 months to 17.5 years) were examined in a cross-sectional study using iohexol clearance and blood sampling at seven time points within 5 h (GFR7p) as the reference method. Median GFR7p was 66 (range 6–153) mL/min/1.73 m2. The performances of six different single time-point formulas (Fleming, Ham and Piepsz, Groth and Aasted, Stake, Jacobsson- and Jacobsson-modified) were validated against the reference. The two-point GFR (GFR2p) was calculated according to the Jødal and Brøchner–Mortensen formula.ResultsThe GFR1p calculated according to Fleming with sampling at 3 h (GFR1p3h-Fleming) had the best overall performance, with 82% of measures within 10% of the reference value (P10). In children with a GFR ≥ 30 mL/min/1.73 m2 (n = 78), the GFR1p3h-Fleming had a P10 of 92.3%, which is not significantly different (p = 0.29) from that of GFR2p (P10 = 96.2%). Considerable differences within and between the different formulas were found for different CKD stages and different time points for blood sampling.ConclusionsFor determination of mGFR in children with CKD and an assumed GFR of ≥ 30 mL/min/1.73 m2 we recommend GFR1p3h-Fleming as the preferred single-point method as an alternative to GFR2p. For children with a GFR < 30 mL/min/1.73 m2, we recommend the slope-GFR with at least two blood samples. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2

Comparative physiology of glomerular filtration rate by plasma clearance of exogenous creatinine and exo-iohexol in six different avian species

“…The latter was confirmed in children by Tøndel et al . (single: >30 mL/min/1.73 m²; double: <30 mL/min/1.73 m²) 26 . In future studies, the use of single- or double-plasma sampling approaches could be evaluated in avian species as well, whereby a mathematical correction for the first fast exponential curve based on the slope-intercept method proposed by Brochner-Mortensen could be incorporated 27 .…”

Growth Differentiation Factor 15 in Children with Chronic Kidney Disease and after Renal Transplantation

“…CKD cohort: children and adolescents < 18 years of age with CKD were included in a cross-sectional study, evaluating biomarkers in CKD and different methods of measuring glomerular filtration rate (mGFR). The children were in a stable phase of their CKD and enrolled at the pediatric departments at Oslo University Hospital and Haukeland University Hospital [10,11].…”

Iohexol plasma clearance for measuring glomerular filtration rate: effect of different ways to calculate the area under the curve

“…at 10 and 20 min, or even only one at 15 min) in the early (distribution) phase may (partially) solve this, but this requires additional discomfort for the patient. Moreover, studies with earlier time-points have reported the same fitting problems [ 24 ].…”

“…Only a few iohexol studies have been published including early (< 120 min) and late time-points [ 5 , 16 , 23 , 24 ] and the ‘accuracy’ of the obtained GFR from the double-exponential decay curve has not been questioned so far. In the current study we have shown that the fitting procedure has significant influence on the obtained coefficients for the double exponential decay curve.…”