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

Tøndel, Camilla; Bolann, Bjørn J.; Salvador, Cathrin Lytomt; Brackman, Damien; Bjerre, Anna; Svarstad, Einar; Brun, Atle

doi:10.1007/s00467-016-3436-z

Cited by 25 publications

(28 citation statements)

References 31 publications

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“…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].…”

Section: Methodsmentioning

confidence: 99%

“…Renal Function. mGFR was measured by using an injection of Omnipaque® (GE Healthcare, Oslo, Norway; i.e., 647 mg iohexol/mL) with blood sampling after 2 and 5 hours as described in a previous publication [10]. In the Tx cohort, 2 mL of Omnipaque® was given to children under 2 years and 5 mL to children over 2 years while the dose was adjusted to the child's weight in the CKD cohort (<10 kg, 1 mL; 10-20 kg, 2 mL; 20-30 kg, 3 mL; 30-40 kg, 4 mL; and >40 kg, 5 mL).…”

Section: Healthy Controlmentioning

confidence: 99%

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

et al. 2020

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Growth differentiation factor 15 (GDF-15) is strongly associated with cardiovascular disease (CVD). The aim of our study was to evaluate plasma and urinary levels of GDF-15 after pediatric renal transplantation (Rtx) and in children with chronic kidney disease (CKD) and its associations to cardiovascular risk factors. In this cross-sectional study, GDF-15 was measured in plasma and urine from 53 children with a renal transplant and 83 children with CKD and related to cardiovascular risk factors (hypertension, obesity, and cholesterol) and kidney function. Forty healthy children served as a control group. Plasma levels of GDF-15 (median and range) for a Tx (transplantation) cohort, CKD cohort, and healthy controls were, respectively, 865 ng/L (463-3039 ng/L), 508 ng/L (183-3279 ng/L), and 390 ng/L (306-657 ng/L). The CKD and Tx cohorts both had significantly higher GDF-15 levels than the control group (p<0.001). Univariate associations between GDF-15 and hyperuricemia (p<0.001), elevated triglycerides (p=0.028), low HDL (p=0.038), and obesity (p=0.028) were found. However, mGFR (p<0.001) and hemoglobin (p<0.001) were the only significant predictors of GDF-15 in an adjusted analysis. Urinary GDF-15/creatinine ratios were 448 ng/mmol (74–5013 ng/mmol) and 540 ng/mmol (5–14960 ng/mmol) in the Tx cohort and CKD cohort, respectively. In the CKD cohort, it was weakly correlated to mGFR (r=−0.343, p=0.002). Plasma levels of GDF-15 are elevated in children with CKD and after Rtx. The levels were not associated with traditional cardiovascular risk factors but strongly associated with renal function.

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Section: Methodsmentioning

confidence: 99%

Section: Healthy Controlmentioning

confidence: 99%

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

et al. 2020

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“…Ninety-six children with chronic kidney disease (CKD) were recruited in a cross-sectional study ( ClinicalTrials.gov Identifier NCT01092260) which has evaluated the two-point methodology [ 23 ]: 54 children at Haukeland University Hospital, Bergen, Norway, and 42 children at Oslo University Hospital, Oslo, Norway. The median age of the included children (55 males, 41 females), was 9.2 years (range 3 months to 17.5 years), the median weight was 28.3 (range 6.6–84.6) kg and the median height was 134 (range 59–177) cm.…”

Section: Methodsmentioning

confidence: 99%

“…Blood samples were drawn at 10, 30 or 60, 120, 180, 210, 240 and 300 min after injection. Additional details are provided in an earlier study published on the same cohort with a focus on two-point methodology [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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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

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Glomerular filtration rate in children and young adults with haemato‐oncological disease and infection is best described by three‐compartment iohexol model

Soeorg

Karu

Saks

et al. 2021

Pediatric Blood & Cancer

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Background: Children with cancer and infection may develop glomerular hyperfiltration. With the aim to determine the prevalence of glomerular hyperfiltration in children and young adults with haemato‐oncological disease and infection, we developed population pharmacokinetic model of iohexol. We further aimed to assess the accuracy of estimated glomerular filtration rate (eGFR) equations and single‐ or two‐point measured GFR (mGFR) formulas compared with GFR based on iohexol clearance from our population pharmacokinetic model (iGFR). Procedure: Hospitalised patients (0.5–25 years) with haemato‐oncological disease and infection were included if their eGFR was ≥80 ml/min/1.73 m2 at the screening visit. Iohexol plasma concentrations were described by population pharmacokinetic model. Bias, precision and accuracy of 23 eGFR equations and 18 mGFR formulas were calculated. Results: Total of 32 iohexol administrations were performed in 28 patients. Median (range) eGFR was 136 ml/min/1.73 m2 (74–234) and age 15.1 years (0.8–26.0). Three‐compartment model with allometric scaling of central, one peripheral compartment and clearance (with power 0.75) to weight fitted the best. Median (range) iGFR was 103 ml/min/1.73 m2 (68–140). All except one eGFR equation overestimated GFR. Lund–Malmö revised eGFR equation performed the best, followed by Gao equation. Of single‐ or two‐point mGFR formulas, 15 overestimated iGFR. Modified Jacobsson formula at 5.5 hours performed the best, followed by Fleming formula at 3 hours. Conclusions: In children and young adults with haemato‐oncological disease and infection, renal function is best described by iohexol clearance from three‐compartment pharmacokinetic model, while eGFR equations and single‐ and two‐point mGFR formulas overestimate iGFR.

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

Cited by 25 publications

References 31 publications

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

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

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

Glomerular filtration rate in children and young adults with haemato‐oncological disease and infection is best described by three‐compartment iohexol model

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