Clinical Trials Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 27, 2022; 14(8): 1621-1632
Published online Aug 27, 2022. doi: 10.4254/wjh.v14.i8.1621
Iohexol plasma and urinary concentrations in cirrhotic patients: A pilot study
Paul Carrier, Alexandre Destere, Baptiste Giguet, Marilyne Debette-Gratien, Marie Essig, Caroline Monchaud, Jean-Baptiste Woillard, Véronique Loustaud-Ratti
Paul Carrier, Baptiste Giguet, Marilyne Debette-Gratien, Véronique Loustaud-Ratti, Department of Liver Disease, Limoges University Hospital Center, U1248, INSERM, F-87000, Limoges, France
Alexandre Destere, Marie Essig, Caroline Monchaud, Jean-Baptiste Woillard, Department of Pharmacology, Toxicology and Centre of Pharmacovigilance, Limoges University Hospital Center, U1248, INSERM, F-87000, Limoges, France
Author contributions: Carrier P, Essig M, Monchaud C, Woillard JB, and Loustaud-Ratti V designed the study; Carrier P, Debette-Gratien M, and Loustaud-Ratti V included the patients; Giguet B collected the data; Destère A and Woillard JB performed the statistical analysis; Carrier P, Destère A, Woillard JB, and Loustaud-Ratti V wrote the manuscript.
Institutional review board statement: The study was reviewed and approved by the French National Review Board and the Independent Ethics Committee of Limoges.
Clinical trial registration statement: This study was registered at EudraCT (2018-002778-35), and on ClinicalTrials.gov (NCT03769597).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest related to the subject.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Véronique Loustaud-Ratti, MD, Professor, Department of Liver Disease, Limoges University Hospital Center, U1248, INSERM, F-87000, Limoges, France. veronique.loustaud-ratti@unilim.fr
Received: March 16, 2022
Peer-review started: March 16, 2022
First decision: April 28, 2022
Revised: May 11, 2022
Accepted: June 24, 2022
Article in press: June 24, 2022
Published online: August 27, 2022
Processing time: 162 Days and 18.1 Hours
Abstract
BACKGROUND

Renal failure is an independent prognostic factor for survival in patients with cirrhosis. Equations to calculate serum creatinine significantly overestimate the glomerular filtration rate (GFR). Plasma clearance of direct biomarkers has been used to improve the accuracy of evaluations of GFR in this population, but no study has simultaneously measured plasma and urinary clearance, which is the gold standard.

AIM

To study calculated plasma and urinary concentrations of iohexol, based on the kinetics of samples collected over 24 h from cirrhotic patients with three different grades of ascites.

METHODS

One dose of iohexol (5 mL) was injected intravenously and plasma concentrations were measured 11 times over 24 h in nine cirrhotic patients. The urinary concentration of iohexol was also measured, in urine collected at 4, 8, 12 and 24 h.

RESULTS

The plasma and urinary curves of iohexol were similar; however, incomplete urinary excretion was detected at 24 h. Within the estimated GFR limits of our population (> 30 and < 120 mL/min/1.73 m²), the median measured GFR (mGFR) was 63.7 mL/min/1.73 m² (range: 41.3–111.3 mL/min/1.73 m²), which was an accurate reflection of the actual GFR. Creatinine-based formulas for estimating GFR showed significant bias and imprecision, while the Brochner–Mortensen (BM) equation accurately estimated the mGFR (r = 0.93).

CONCLUSION

Plasma clearance of iohexol seems useful for determining GFR regardless of the ascites grade. We will secondly devise a pharmacokinetics model requiring fewer samples andvalidate the BM equation.

Keywords: Cirrhosis; Glomerular filtration Rate; Iohexol; Pharmacokinetics; Brochner-Mortensen

Core tip: Accurately evaluating glomerular filtration rate (GFR) in cirrhotic patients is critical to optimize their management and identify patients who should be prioritized for liver transplantation, and informs discussion of double liver–kidney transplantation. Until now, no formula or direct method for measuring GFR was available. This prospective pilot study is the first to systematically describe the plasma and urinary concentrations of iohexol, based on the kinetics of samples collected over 24 h from cirrhotic patients with three different ascites grades. The next step will be to construct a Bayesian estimator from a limited number of samples.