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Published in: Pediatric Nephrology 4/2018

Open Access 01-04-2018 | Original Article

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

Authors: Camilla Tøndel, Cathrin Lytomt Salvador, Karl Ove Hufthammer, Bjørn Bolann, Damien Brackman, Anna Bjerre, Einar Svarstad, Atle Brun

Published in: Pediatric Nephrology | Issue 4/2018

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Abstract

Background

The 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.

Methods

Ninety-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.

Results

The 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.

Conclusions

For 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.
Literature
1.
go back to reference Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedPubMedCentral Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedPubMedCentral
2.
go back to reference Krutzen E, Back SE, Nilsson-Ehle I, Nilsson-Ehle P (1984) Plasma clearance of a new contrast agent, iohexol: a method for the assessment of glomerular filtration rate. J Lab Clin Med 104:955–961PubMed Krutzen E, Back SE, Nilsson-Ehle I, Nilsson-Ehle P (1984) Plasma clearance of a new contrast agent, iohexol: a method for the assessment of glomerular filtration rate. J Lab Clin Med 104:955–961PubMed
3.
go back to reference Schwartz GJ, Furth S, Cole SR, Warady B, Munoz A (2006) Glomerular filtration rate via plasma iohexol disappearance: pilot study for chronic kidney disease in children. Kidney Int 69:2070–2077CrossRefPubMed Schwartz GJ, Furth S, Cole SR, Warady B, Munoz A (2006) Glomerular filtration rate via plasma iohexol disappearance: pilot study for chronic kidney disease in children. Kidney Int 69:2070–2077CrossRefPubMed
4.
go back to reference Schwartz GJ, Abraham AG, Furth SL, Warady BA, Munoz A (2010) Optimizing iohexol plasma disappearance curves to measure the glomerular filtration rate in children with chronic kidney disease. Kidney Int 77:65–71CrossRefPubMedPubMedCentral Schwartz GJ, Abraham AG, Furth SL, Warady BA, Munoz A (2010) Optimizing iohexol plasma disappearance curves to measure the glomerular filtration rate in children with chronic kidney disease. Kidney Int 77:65–71CrossRefPubMedPubMedCentral
5.
go back to reference Brown SC, O’Reilly PH (1991) Iohexol clearance for the determination of glomerular filtration rate in clinical practice: evidence for a new gold standard. J Urol 146:675–679CrossRefPubMed Brown SC, O’Reilly PH (1991) Iohexol clearance for the determination of glomerular filtration rate in clinical practice: evidence for a new gold standard. J Urol 146:675–679CrossRefPubMed
6.
go back to reference Gaspari F, Perico N, Ruggenenti P, Mosconi L, Amuchastegui CS, Guerini E, Daina E, Remuzzi G (1995) Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate. J Am Soc Nephrol 6:257–263PubMed Gaspari F, Perico N, Ruggenenti P, Mosconi L, Amuchastegui CS, Guerini E, Daina E, Remuzzi G (1995) Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate. J Am Soc Nephrol 6:257–263PubMed
7.
go back to reference Lindblad HG, Berg UB (1994) Comparative evaluation of iohexol and inulin clearance for glomerular filtration rate determinations. Acta Paediatr 83:418–422CrossRefPubMed Lindblad HG, Berg UB (1994) Comparative evaluation of iohexol and inulin clearance for glomerular filtration rate determinations. Acta Paediatr 83:418–422CrossRefPubMed
8.
go back to reference Brøchner-Mortensen J (1972) A simple method for the determination of glomerular filtration rate. Scand J Clin Lab Invest 30:271–274CrossRefPubMed Brøchner-Mortensen J (1972) A simple method for the determination of glomerular filtration rate. Scand J Clin Lab Invest 30:271–274CrossRefPubMed
9.
go back to reference Brøchner-Mortensen J, Haahr J, Christoffersen J (1974) A simple method for accurate assessment of the glomerular filtration rate in children. Scand J Clin Lab Invest 33:140–143CrossRefPubMed Brøchner-Mortensen J, Haahr J, Christoffersen J (1974) A simple method for accurate assessment of the glomerular filtration rate in children. Scand J Clin Lab Invest 33:140–143CrossRefPubMed
10.
go back to reference Fleming JS, Wilkinson J, Oliver RM, Ackery DM, Blake GM, Waller DG (1991) Comparison of radionuclide estimation of glomerular filtration rate using technetium 99m diethylenetriaminepentaacetic acid and chromium 51 ethylenediaminetetraacetic acid. Eur J Nucl Med 18:391–395CrossRefPubMed Fleming JS, Wilkinson J, Oliver RM, Ackery DM, Blake GM, Waller DG (1991) Comparison of radionuclide estimation of glomerular filtration rate using technetium 99m diethylenetriaminepentaacetic acid and chromium 51 ethylenediaminetetraacetic acid. Eur J Nucl Med 18:391–395CrossRefPubMed
11.
go back to reference Fleming JS, Zivanovic MA, Blake GM, Burniston M, Cosgriff PS (2004) Guidelines for the measurement of glomerular filtration rate using plasma sampling. Nucl Med Commun 25:759–769CrossRefPubMed Fleming JS, Zivanovic MA, Blake GM, Burniston M, Cosgriff PS (2004) Guidelines for the measurement of glomerular filtration rate using plasma sampling. Nucl Med Commun 25:759–769CrossRefPubMed
12.
go back to reference Jacobsson L (1983) A method for the calculation of renal clearance based on a single plasma sample. Clin Physiol 3:297–305CrossRefPubMed Jacobsson L (1983) A method for the calculation of renal clearance based on a single plasma sample. Clin Physiol 3:297–305CrossRefPubMed
13.
go back to reference Stake G, Monclair T (1991) A single plasma sample method for estimation of the glomerular filtration rate in infants and children using iohexol, I: establishment of a body weight-related formula for the distribution volume of iohexol. Scand J Clin Lab Invest 51:335–342CrossRefPubMed Stake G, Monclair T (1991) A single plasma sample method for estimation of the glomerular filtration rate in infants and children using iohexol, I: establishment of a body weight-related formula for the distribution volume of iohexol. Scand J Clin Lab Invest 51:335–342CrossRefPubMed
14.
go back to reference Gaspari F, Guerini E, Perico N, Mosconi L, Ruggenenti P, Remuzzi G (1996) Glomerular filtration rate determined from a single plasma sample after intravenous iohexol injection: is it reliable? J Am Soc Nephrol 7:2689–2693PubMed Gaspari F, Guerini E, Perico N, Mosconi L, Ruggenenti P, Remuzzi G (1996) Glomerular filtration rate determined from a single plasma sample after intravenous iohexol injection: is it reliable? J Am Soc Nephrol 7:2689–2693PubMed
16.
go back to reference Groth S, Aasted M (1981) 51Cr-EDTA clearance determined by one plasma sample. Clin Physiol 1:417–425CrossRefPubMed Groth S, Aasted M (1981) 51Cr-EDTA clearance determined by one plasma sample. Clin Physiol 1:417–425CrossRefPubMed
17.
go back to reference Itoh K, Matsuyama T (2002) The single-plasma-sample method for determining the glomerular filtration rate with Tc-99m-diethylenetriamine pentaacetic acid in childhood and adolescence: is it age-dependent? Ann Nucl Med 16:541–548CrossRefPubMed Itoh K, Matsuyama T (2002) The single-plasma-sample method for determining the glomerular filtration rate with Tc-99m-diethylenetriamine pentaacetic acid in childhood and adolescence: is it age-dependent? Ann Nucl Med 16:541–548CrossRefPubMed
18.
go back to reference Eriksen BO, Mathisen UD, Melsom T, Ingebretsen OC, Jenssen TG, Njølstad I, Solbu MD, Toft I (2010) Cystatin C is not a better estimator of GFR than plasma creatinine in the general population. Kidney Int 78:1305–1311CrossRefPubMed Eriksen BO, Mathisen UD, Melsom T, Ingebretsen OC, Jenssen TG, Njølstad I, Solbu MD, Toft I (2010) Cystatin C is not a better estimator of GFR than plasma creatinine in the general population. Kidney Int 78:1305–1311CrossRefPubMed
19.
go back to reference McMeekin H, Wickham F, Barnfield M, Burniston M (2016) A systematic review of single-sample glomerular filtration rate measurement techniques and demonstration of equal accuracy to slope-intercept methods. Nucl Med Commun 37:743–755CrossRefPubMed McMeekin H, Wickham F, Barnfield M, Burniston M (2016) A systematic review of single-sample glomerular filtration rate measurement techniques and demonstration of equal accuracy to slope-intercept methods. Nucl Med Commun 37:743–755CrossRefPubMed
20.
go back to reference Groth S, Aasted M (1984) 51Cr-EDTA clearance determined by one plasma sample in children. Clin Physiol 4:75–83CrossRefPubMed Groth S, Aasted M (1984) 51Cr-EDTA clearance determined by one plasma sample in children. Clin Physiol 4:75–83CrossRefPubMed
21.
go back to reference Stake G, Monn E, Rootwelt K, Monclair T (1991) A single plasma sample method for estimation of the glomerular filtration rate in infants and children using iohexol, II: establishment of the optimal plasma sampling time and a comparison with the 99Tcm-DTPA method. Scand J Clin Lab Invest 51:343–348CrossRefPubMed Stake G, Monn E, Rootwelt K, Monclair T (1991) A single plasma sample method for estimation of the glomerular filtration rate in infants and children using iohexol, II: establishment of the optimal plasma sampling time and a comparison with the 99Tcm-DTPA method. Scand J Clin Lab Invest 51:343–348CrossRefPubMed
22.
go back to reference Fleming JS, Persaud L, Zivanovic MA (2005) A general equation for estimating glomerular filtration rate from a single plasma sample. Nucl Med Commun 26:743–748CrossRefPubMed Fleming JS, Persaud L, Zivanovic MA (2005) A general equation for estimating glomerular filtration rate from a single plasma sample. Nucl Med Commun 26:743–748CrossRefPubMed
23.
go back to reference Tøndel C, Bolann B, Salvador CL, Brackman D, Bjerre A, Svarstad E, Brun A (2017) Iohexol plasma clearance in children: validation of multiple formulas and two-point sampling times. Pediatr Nephrol 32:311–320CrossRefPubMed Tøndel C, Bolann B, Salvador CL, Brackman D, Bjerre A, Svarstad E, Brun A (2017) Iohexol plasma clearance in children: validation of multiple formulas and two-point sampling times. Pediatr Nephrol 32:311–320CrossRefPubMed
24.
go back to reference Sapirstein LA, Vidt DG, Mandel MJ, Hanusek G (1955) Volumes of distribution and clearances of intravenously injected creatinine in the dog. Am J Phys 181:330–336 Sapirstein LA, Vidt DG, Mandel MJ, Hanusek G (1955) Volumes of distribution and clearances of intravenously injected creatinine in the dog. Am J Phys 181:330–336
25.
go back to reference Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height–weight formula validated in infants, children, and adults. J Pediatr 93:62–66CrossRefPubMed Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height–weight formula validated in infants, children, and adults. J Pediatr 93:62–66CrossRefPubMed
26.
go back to reference Ham HR, Piepsz A (1991) Estimation of glomerular filtration rate in infants and in children using a single-plasma sample method. J Nucl Med 32:1294–1297PubMed Ham HR, Piepsz A (1991) Estimation of glomerular filtration rate in infants and in children using a single-plasma sample method. J Nucl Med 32:1294–1297PubMed
27.
go back to reference Brown LD, Cai T, DasGupta A (2001) Interval estimation for a binomial proportion. Statist Sci 16:101–133 Brown LD, Cai T, DasGupta A (2001) Interval estimation for a binomial proportion. Statist Sci 16:101–133
28.
go back to reference Jødal L, Brøchner-Mortensen J (2009) Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part I: analytically correct relationship between total and one-pool clearance. Scand J Clin Lab Invest 69:305–313CrossRefPubMed Jødal L, Brøchner-Mortensen J (2009) Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part I: analytically correct relationship between total and one-pool clearance. Scand J Clin Lab Invest 69:305–313CrossRefPubMed
29.
go back to reference Brøchner-Mortensen J, Jødal L (2009) Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part II: empirically determined relationships between total and one-pool clearance. Scand J Clin Lab Invest 69:314–322CrossRefPubMed Brøchner-Mortensen J, Jødal L (2009) Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part II: empirically determined relationships between total and one-pool clearance. Scand J Clin Lab Invest 69:314–322CrossRefPubMed
30.
go back to reference Core Team R (2017) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. www.R-project.org Core Team R (2017) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. www.​R-project.​org
31.
go back to reference Delanaye P, Ebert N, Melsom T, Gaspari F, Mariat C, Cavalier E, Bjork J, Christensson A, Nyman U, Porrini E, Remuzzi G, Ruggenenti P, Schaeffner E, Soveri I, Sterner G, Eriksen BO, Back SE (2016) Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: how to measure glomerular filtration rate with iohexol? Clin Kidney J 9:682–699CrossRefPubMedPubMedCentral Delanaye P, Ebert N, Melsom T, Gaspari F, Mariat C, Cavalier E, Bjork J, Christensson A, Nyman U, Porrini E, Remuzzi G, Ruggenenti P, Schaeffner E, Soveri I, Sterner G, Eriksen BO, Back SE (2016) Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: how to measure glomerular filtration rate with iohexol? Clin Kidney J 9:682–699CrossRefPubMedPubMedCentral
32.
go back to reference Delanaye P, Melsom T, Ebert N, Back SE, Mariat C, Cavalier E, Bjork J, Christensson A, Nyman U, Porrini E, Remuzzi G, Ruggenenti P, Schaeffner E, Soveri I, Sterner G, Eriksen BO, Gaspari F (2016) Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2: why to measure glomerular filtration rate with iohexol? Clin Kidney J 9:700–704CrossRefPubMedPubMedCentral Delanaye P, Melsom T, Ebert N, Back SE, Mariat C, Cavalier E, Bjork J, Christensson A, Nyman U, Porrini E, Remuzzi G, Ruggenenti P, Schaeffner E, Soveri I, Sterner G, Eriksen BO, Gaspari F (2016) Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2: why to measure glomerular filtration rate with iohexol? Clin Kidney J 9:700–704CrossRefPubMedPubMedCentral
Metadata
Title
Iohexol plasma clearance in children: validation of multiple formulas and single-point sampling times
Authors
Camilla Tøndel
Cathrin Lytomt Salvador
Karl Ove Hufthammer
Bjørn Bolann
Damien Brackman
Anna Bjerre
Einar Svarstad
Atle Brun
Publication date
01-04-2018
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 4/2018
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-017-3841-y

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