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
Highlights
For determination of measured GFR (mGFR) in children with chronic kidney disease (CKD) and an assumed glomerular filtration rate (GFR) of ≥ 30 mL/min/1.73 m2 we recommend GFR1p3h-Fleming as the preferred single-point method as an alternative to GFR2p
The low accuracy of formulas for estimating glomerular filtration rate (GFR) in children has long been a major challenge, Pediatr Nephrol (2018) 33:683–696 with studies showing that less than 50% of the GFR levels estimated using formulas based on serum cystatin C, creatinine and/or urea are within ± 10% of the gold standard GFR measurement [1]
More accurate determinations of kidney function are needed with a feasible measured GFR methodology based on the plasma clearance of an exogenous GFR marker
Summary
The low accuracy of formulas for estimating glomerular filtration rate (GFR) in children has long been a major challenge, Pediatr Nephrol (2018) 33:683–696 with studies showing that less than 50% of the GFR levels estimated (eGFR) using formulas based on serum cystatin C, creatinine and/or urea are within ± 10% of the gold standard GFR measurement [1]. A modification of the Jacobsson formula for pediatric use was published the same year by Stake and colleagues; these authors recommended a sampling point at 3 h based on 99TCm-DTPA clearance [3, 21]. The Fleming formula first and foremost was suggested as a quality control method for the slope-intercept technique [22], a recent study [19] reports results arguing for the GFR1p-Fleming as a potential stand-alone formula for pediatric nephrology care. 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. Considerable differences within and between the different formulas were found for different CKD stages and different time points for blood sampling
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