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

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          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 m 2. 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.

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          Most cited references24

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          A simple method for the determination of glomerular filtration rate.

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            Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate.

            Renal clearance of inulin is the best available indicator of GFR but cannot be used routinely for clinical purposes and is also difficult to perform for clinical investigation when repeated measurements are required. The aim of this study was to find a reliable alternative to inulin clearance that would allow one to avoid the use of radioactivity and problems related to the continuous infusion of the marker. The plasma clearance of unlabeled iohexol, a nonionic contrast agent, was used. Forty-one patients (creatinine clearance 6 to 160 mL/min per 1.73 m2) underwent simultaneous measurements of renal clearance of inulin and plasma clearance of iohexol. Iohexol was given as a single iv dose, and blood samples were drawn up to 600 min after the administration. Iohexol concentrations (by HPLC) were analyzed by a two-compartment, open-model system. A highly significant correlation between the plasma clearance of iohexol and the renal clearance of inulin over a wide range of GFR values was found. By analyzing the data with a simplified method that uses a one-compartment model corrected with the Bröchner-Mortensen formula, an excellent correlation with the inulin clearance was also observed. When only patients with moderate to severe renal failure were considered, a significant correlation between the two methods was found. A further comparison between GFR determined with iohexol and iopromide, a new low-osmolarity, low-viscosity contrast medium, was also performed in a subgroup of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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              Glomerular filtration rate via plasma iohexol disappearance: pilot study for chronic kidney disease in children.

              To guide the design of a nation-wide cohort study of chronic kidney disease in children, we determined how iohexol plasma disappearance curves could be used in children to measure glomerular filtration rate (GFR). Iohexol (5 ml) was administered intravenously and blood samples were obtained at 10, 20, 30, 60, 120, 240, 300, and 360 min after injection (N=29) and assayed by high performance liquid chromatography. Four urines were also collected following the injection. Intra-assay coefficient of variation (CV) in serum was 1.3% at 100 mg/l, 2.6% at 15 mg/l, and 3.4% for duplicate unknowns. GFR(9) was computed from iohexol dose and area under the nine-point blood disappearance curve, using double exponential modeling. Only 2.8% of 254 data points deviated by >3 CV from the curves. GFR(4) calculated from 10, 30, 120, and 300 min points correlated well with GFR(9) (r=0.999) and showed no bias (means+/-s.d. of GFR(9) and GFR(4)=59.3+/-36.3 and 59.4+/-36.0 ml/min per 1.73 m(2)). Relationship of GFR(9) and one-compartment GFR followed quadratic equation as previously reported by Brochner-Mortensen, allowing GFR to be calculated from 120 and 300 min points. This GFR(2) correlated well with GFR(9) (r=0.986). Estimated GFR from Schwartz height/creatinine formula correlated with GFR(9)(r=0.934) but overestimated GFR by 12.2 ml/min per 1.73 m(2). Urine iohexol clearance was poorly correlated (r=0.770) with GFR(9) owing to variability in urine collections (median CV=24%). GFR can be measured accurately using four-point iohexol plasma disappearance (in most cases, two points suffice); estimated GFR and urinary clearances are less useful.
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                Author and article information

                Contributors
                + 47-55975000 , + 47-55975701 , camilla.tondel@helse-bergen.no
                Journal
                Pediatr Nephrol
                Pediatr. Nephrol
                Pediatric Nephrology (Berlin, Germany)
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0931-041X
                1432-198X
                1 July 2016
                1 July 2016
                2017
                : 32
                : 2
                : 311-320
                Affiliations
                [1 ]Department of Pediatrics, Haukeland University Hospital, N-5021 Bergen, Norway
                [2 ]Department of Clinical Medicine, University of Bergen, Bergen, Norway
                [3 ]Department of Clinical Science, University of Bergen, Bergen, Norway
                [4 ]Laboratory for Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway
                [5 ]Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
                [6 ]Department of Pediatrics, Oslo University Hospital, Oslo, Norway
                [7 ]Department of Medicine, Haukeland University Hospital, Bergen, Norway
                Article
                3436
                10.1007/s00467-016-3436-z
                5203838
                27369694
                35360d9b-3098-4a0d-b886-e06a07608da1
                © The Author(s) 2016

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 31 December 2015
                : 2 May 2016
                : 17 May 2016
                Funding
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/501100005029, Helse Vest Regionalt Helseføretak;
                Funded by: The Norwegian Society of Nephrology
                Funded by: Oslo University Hospital
                Funded by: Haukeland University Hospital
                Categories
                Original Article
                Custom metadata
                © IPNA 2017

                Nephrology
                glomerular filtration rate,child,chronic kidney disease,renal function,method
                Nephrology
                glomerular filtration rate, child, chronic kidney disease, renal function, method

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