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      A Simple Method to Measure Renal Function in Swine by the Plasma Clearance of Iohexol

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          Abstract

          There is no simple method to measure glomerular filtration rate (GFR) in swine, an established model for studying renal disease. We developed a protocol to measure GFR in conscious swine by using the plasma clearance of iohexol. We used two groups, test and validation, with eight animals each. Ten milliliters of iohexol (6.47 g) was injected into the marginal auricular vein and blood samples (3 mL) were collected from the orbital sinus at different points after injection. GFR was determined using two models: two-compartment (CL2: all samples) and one-compartment (CL1: the last six samples). In the test group, CL1 overestimated CL2 by ~30%: CL2 = 245 ± 93 and CL1 = 308 ± 123 mL/min. This error was corrected by a first-order polynomial quadratic equation to CL1, which was considered the simplified method: SM = −47.909 + (1.176xCL1) − (0.00063968xCL1 2). The SM showed narrow limits of agreement with CL2, a concordance correlation of 0.97, and a total deviation index of 14.73%. Similar results were obtained for the validation group. This protocol is reliable, reproducible, can be performed in conscious animals, uses a single dose of the marker, and requires a reduced number of samples, and avoids urine collection. Finally, it presents a significant improvement in animal welfare conditions and handling necessities in experimental trials.

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          Physiological parameters in laboratory animals and humans.

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            A simple method for the determination of glomerular filtration rate.

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              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?

              While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non-ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                12 January 2018
                January 2018
                : 19
                : 1
                : 232
                Affiliations
                [1 ]Research Unit, University Hospital of the Canary Islands, 38320 La Laguna, Tenerife, Spain; luislimasergio@ 123456gmail.com (S.L.-L.); natalianegrinmena@ 123456gmail.com (N.N.-M.); ajimenezsosa@ 123456gmail.com (A.J.-S.); hjimenezhdez@ 123456gmail.com (H.J.-H.)
                [2 ]Comparative Physiology Group, SGIT-INIA, 28040 Madrid, Spain; garcia.consolacion@ 123456inia.es (C.G.-C.); astiz.susana@ 123456gmail.com (S.A.); bulnes@ 123456inia.es (A.G.-B.)
                [3 ]Faculty of Veterinary, Universidad Complutense de Madrid, 28040 Madrid, Spain; mvgomez@ 123456ucm.es
                [4 ]IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases ‘Aldo & Cele Daccò’, 24020 Ranica (BG), Italy; fabiola.carrara@ 123456marionegri.it (F.C.); flavio.gaspari@ 123456marionegri.it (F.G.)
                [5 ]Instituto Tecnologías Biomédicas (ITB), University of La Laguna, 38320 Tenerife, Spain
                Author notes
                [* ]Correspondence: esteban.l.porrini@ 123456gmail.com ; Tel.: +34-922-678-116
                Author information
                https://orcid.org/0000-0002-8916-2086
                https://orcid.org/0000-0002-9718-0903
                https://orcid.org/0000-0001-5941-3481
                https://orcid.org/0000-0002-0917-4475
                Article
                ijms-19-00232
                10.3390/ijms19010232
                5796180
                29329247
                2c0c793a-4e35-4850-95b2-8f401adb3d9a
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 October 2017
                : 09 January 2018
                Categories
                Article

                Molecular biology
                renal function,iohexol plasma clearance,swine model
                Molecular biology
                renal function, iohexol plasma clearance, swine model

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