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

Abstract

Background: In children, estimated glomerular filtration rate (eGFR) methods are hampered by inaccuracy, hence there is an obvious need for safe, simplified, and accurate measured GFR (mGFR) methods. The aim of this study was to evaluate different formulas and determine the optimal sampling points for calculating mGFR based on iohexol clearance measurements on blood samples drawn at two time points (GFR2p).

Methods: The GFR of 96 children with different stages of chronic kidney disease (CKD) (median age 9.2 years, range 3 months to 17.5 years) was determined using the iohexol plasma clearance, with blood sampling at seven time points within 5 h (GFR7p) as the reference method. Median GFR7p was 65.9 (range 6.3-153) mL/min/1.73 m2. The performance of seven different formulas with early and late normalization to body surface area (BSA) was validated against the reference.

Results: The highest percentage (95.8 %) of GFR2p within 10 % of the reference was calculated using the formula of Jødal and Brøchner-Mortensen (JBM) from 2009, with sampling at 2 and 5 h. Normalization to BSA before correction of the distribution phase improved the performance of the original Brøchner-Mortensen method from 1972; P10 of 92.7 % compared to P10 of 82.3 % with late normalization, and a similar result was obtained with other formulas.

Conclusions: GFR2p performed well across a wide spectrum of GFR levels with the JBM formula. Several other formulas tested performed well provided that early BSA normalization was performed. Blood sampling at 2 and 5 h is recommended for an optimal GFR2p assessment.

Trial registration: ClinicalTrials.gov NCT01092260.

Keywords: Child; Chronic kidney disease; Glomerular filtration rate; Method; Renal function.

Conflict of interest statement

Compliance with ethical standards The study was approved by the Regional Ethics Committee of Western Norway and an informed consent form was signed in all cases. The study was performed in adherence to the Declaration of Helsinki. Funding source The study was supported by grants from the Health Trust of Western Norway, The Norwegian Society of Nephrology, Haukeland University Hospital and Oslo University Hospital Financial disclosure The authors have no financial relationships relevant to this article to disclose. Conflict of interest The authors have no conflicts of interest to disclose. Clinical trial registration ClinicalTrials.gov, Identifier NCT01092260, https://ichgcp.net/clinical-trials-registry/NCT01092260?term=tondel&rank=2

Figures

Fig. 1

Accuracy of 7 different formulas for calculating measured GFR (mGFR) based on iohexol clearance measurements (see Table 1 for the formulas and the Introduction for more details). GFR (mL/min/1.73 m2) was calculated by 2-point GFR (GFR2p) using the different formulas as indicated and with blood sampling at 2 and 5 h after injection. N = 96 patients. Color coding of graph: Black Fraction of results within 5 % deviation of the reference method (GFR7p: GFR measured by the iohexol clearance method with blood sampling at 7 time points within 5 h), gray additional fraction within 10 % deviation of reference method, white additional fraction within 15 % deviation of reference method. Left column of each column pair Body surface area (BSA) normalization to 1.73 m2 performed “before” the mathematical correction for the distribution phase, right column of each column pair normalization performed “after” the entire GFR calculation was completed

Fig. 2

Bland–Altman plots between the glomerular filtration rate (GFR) (mL/min/1.73 m2) calculated according to reference method (GFR7p) and GFR calculated according to the BMadultafter formula (a), the BMadultbefore formula (b), and the JBM formula (c). a GFR was calculated by GFR2p according to the 1972 formula of Brøchner–Mortensen (BMadultafter) with sampling at 2 and 5 h after injection. BSA normalization to 1.73 m2 was performed after the entire GFR calculation was completed. N = 96 patients. Y-axis Difference between BMadultafter and the reference method (GFR7p), X-axis mean of the two methods. Dotted lines ±10 % difference. b GFR was calculated by GFR2p according to the 1972 formula of Brøchner–Mortensen (BMadultbefore) with sampling at 2 and 5 h after injection. BSA normalization to 1.73 m2 was performed before the mathematical correction for the distribution phase. N = 96 patients. Y-axis Difference between BMadultbefore and the reference method (GFR7p), X-axis mean of the two methods. Dotted lines ±10 % difference. c GFR was calculated by GFR2p according to the 2009 formula of Jødal and Brøchner–Mortensen (JBM) with sampling at 2 and 5 h after injection. N = 96 patients. Y-axis Difference between JBM and the reference method (GFR7p), X-axis mean of the two methods. Dotted lines ±10 % difference