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Validation of a continuous infusion of low dose Iohexol to measure glomerular filtration rate: randomised clinical trial.

Dixon, JJ; Lane, K; Dalton, RN; Turner, C; Grounds, RM; MacPhee, IA; Philips, BJ (2015) Validation of a continuous infusion of low dose Iohexol to measure glomerular filtration rate: randomised clinical trial. J Transl Med, 13. p. 58. ISSN 1479-5876
SGUL Authors: MacPhee, Iain Angus MacGregor Philips, Barbara

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INTRODUCTION: There is currently no accurate method of measuring glomerular filtration rate (GFR) during acute kidney injury (AKI). Knowledge of how much GFR varies in stable subjects is necessary before changes in GFR can be attributed to AKI. We have designed a method of continuous measurement of GFR intended as a research tool to time effects of AKI. The aims of this crossover trial were to establish accuracy and precision of a continuous infusion of low dose Iohexol (CILDI) and variation in GFR in stable volunteers over a range of estimated GFR (23-138 mL/min/1.73 m(2)). METHODS: We randomised 17 volunteers to GFR measurement by plasma clearance (PC) and renal clearance (RC) of either a single bolus of Iohexol (SBI; routine method), or of a continuous infusion of low dose Iohexol (CILDI; experimental method) at 0.5 mL/h for 12 h. GFR was measured by the alternative method after a washout period (4-28 days). Iohexol concentration was measured by high performance liquid chromatography/electrospray tandem mass spectrometry and time to steady state concentration (Css) determined. RESULTS: Mean PC was 76.7 ± 28.5 mL/min/1.73 m(2) (SBI), and 78.9 ± 28.6 mL/min/1.73 m(2) (CILDI), p = 0.82. No crossover effects occurred (p = 0.85). Correlation (r) between the methods was 0.98 (p < 0.0001). Bias was 2.2 mL/min/1.73 m(2) (limits of agreement -8.2 to 12.6 mL/min/1.73 m(2)) for CILDI. PC overestimated RC by 7.1 ± 7.3 mL/min/1.73 m(2). Mean intra-individual variation in GFR (CILDI) was 10.3% (p < 0.003). Mean ± SD Css was 172 ± 185 min. CONCLUSION: We hypothesise that changes in GFR >10.3% depict evolving AKI. If this were applicable to AKI, this is less than the 50% change in serum creatinine currently required to define AKI. CILDI is now ready for testing in patients with AKI. TRIAL REGISTRATION: This trial was registered with the European Union Clinical Trials Register (, registration number: 2010-019933-89 .

Item Type: Article
Additional Information: © Dixon et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Keywords: Adult, Aged, Demography, Dose-Response Relationship, Drug, Female, Glomerular Filtration Rate, Humans, Iohexol, Male, Middle Aged, Time Factors, Humans, Iohexol, Glomerular Filtration Rate, Demography, Dose-Response Relationship, Drug, Time Factors, Adult, Aged, Middle Aged, Female, Male, Immunology, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Clinical Education (INMECE )
Journal or Publication Title: J Transl Med
ISSN: 1479-5876
Language: eng
12 February 2015Published
20 January 2015Accepted
Publisher License: Creative Commons: Attribution 4.0
PubMed ID: 25885409
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