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Continuous Infusion of Low-Dose Iohexol Measures Changing Glomerular Filtration Rate in Critically Ill Patients

Dixon, John J. MSc1,2,3; Lane, Katie MBBS1,2; Dalton, R. Neil PhD4; Turner, Charles PhD4; MacPhee, Iain A. M. DPhil1,3; Chis Ster, Irina PhD5; Philips, Barbara J. MD1,2

doi: 10.1097/CCM.0000000000002870
Online Clinical Investigations
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Objective: Measurement of changing glomerular filtration rate in acute kidney injury remains problematic. We have previously used a continuous infusion of low-dose Iohexol to measure glomerular filtration rate in stable subjects and postulate that changes greater than 10.3% in critically ill patients indicate acute kidney injury. Our objective is to explore the extent to which continuous infusion of low-dose Iohexol can be a measure of changing glomerular filtration rate during acute kidney injury.

Design: Clinical observational exploratory study.

Setting: Adult ICU.

Patients: Three patient groups were recruited: nephrectomy group: predictable onset of acute kidney injury and outcome (n = 10); surgery group: predictable onset of acute kidney injury, unpredictable outcome (n = 11); and acute kidney injury group: unpredictable onset of acute kidney injury and outcome (n = 13).

Interventions: Continuous infusion of low-dose Iohexol was administered for 24–80 hours. Plasma (ClP) and renal (ClR) Iohexol clearances were measured at timed intervals.

Measurements and Main Results: Kidney Disease: Improved Global Outcomes acute kidney injury criteria were fulfilled in 22 patients (nephrectomy = 5, surgery = 4, and acute kidney injury = 13); continuous infusion of low-dose Iohexol demonstrated acute kidney injury in 29 patients (nephrectomy = 10, surgery = 8, acute kidney injury = 11). Dynamic changes in glomerular filtration rate were tracked in all patients. In the nephrectomy group, ClR decreased by an expected 50% (50.8% ± 11.0%). Agreement between ClP and ClR improved with increasing duration of infusion: bias of ClP versus ClR at 48 hours was –0.1 ± 3.6 mL/min/1.73 m2 (limits of agreement: –7.2 to 7.1 mL/min/1.73 m2). Coefficient of variation of laboratory sample analysis was 2.4%.

Conclusions: Continuous infusion of low-dose Iohexol is accurate and precise when measuring glomerular filtration rate and tracks changes in patients with differing risks of acute kidney injury. Continuous infusion of low-dose Iohexol may provide a useful standard against which to test novel biomarkers for the diagnosis of acute kidney injury.

1Institute of Medical and Biomedical Education, St. George’s, University of London, London, United Kingdom.

2Department of Critical Care, St. George’s University Hospitals NHS Foundation Trust, London, United Kingdom.

3Department of Renal and Transplantation Medicine, St. George’s University Hospitals NHS Foundation Trust, London, United Kingdom.

4Wellchild Laboratory, King’s College, London, Evelina Children’s Hospital, London, United Kingdom.

5Institute of Infection and Immunity, St. George’s, University of London, London, United Kingdom.

Dr. Dixon carried out the study, as part of a PhD project, and was responsible for all aspects of the research project, including writing the article. Drs. Turner and Dalton were involved in experimental design, sample analysis, and statistical analysis of the laboratory samples. Drs. Lane, MacPhee, and Philips were involved in experimental design and statistical analysis. Dr. Ster reviewed the study statistical methods and results and provided additional analyses. Drs. MacPhee and Philips provided final editorial changes prior to submission. All authors approved the final version.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported by Intensive Care Foundation, Intensive Care Society, London, United Kingdom, and St. George’s Hospital Medical Research Charity, St. George’s Hospital, London, United Kingdom.

Dr. Lane’s institution received funding from Intensive Care Society and St George’s Hospital Charity. Dr. Dalton’s institution received funding from Clinical Sciences Division, St George’s Medical School University of London and he disclosed work for hire. Drs. Dalton and Turner disclosed that they are founding Directors (and Dr. Dalton is a Board Member) of SpOtOn Clinical Diagnostics, a University/Trust spin-out company incorporated in 2011 specializing in analytical consultancy and services with an expertise in renal function. Drs. Turner and Philips’s institutions received funding from a Young Investigator award to J. Dixon, from Intensive Care Foundation (c/o Intensive Care Society), for £15,000, and from a St. George’s Hospital Medical Research Charity grant, for £5000. Dr. MacPhee’s institution received funding from Young Investigator award, from Intensive Care Foundation (c/o Intensive Care Society) and St. George’s Hospital Medical Research Charity grant, and he received funding from Chiesi (honorarium for: delivering teaching, lecturing, and writing the article). Dr. Philips’ institution received funding from Aridis, principal investigator for their UK studies in to Monoclonal Ab treatment of specific infections (unrelated to her acute kidney injury work); she received funding from St George’s hospital medical research charity for £5,000 (money for consumables in the study); and she disclosed she is a council member of the Intensive Care Society 2013–2016 (travel and accommodation paid) The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: bphilips@sgul.ac.uk

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