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
ARTICLE HIGHLIGHTS
Research background

To date, no method for measuring the glomerular filtration rate (GFR) based on either creatinine or an exogenous marker, which is both reliable and applicable in clinical practice in cirrhotic patients with different degrees of decompensation, is available.

Research motivation

We urgently need accurate methods to measure GFR in cirrhotic patients; renal failure being a key prognostic factor in decompensated cirrhosis, particularly in the pre and post-transplant period.

Research objectives

Describing the complete pharmacokinetic (PK) study of iohexol in blood and urine as an appropriate and inexpensive marker is essential to subsequently construct a PK model from a limited number of samples.

Research methods

This pilot study included nine patients with different ascites grades, who received a single 5-mL bolus of iohexol, with the collection of 11 blood samples and all the urine volume (in four samples) over a period of 24 h.

Research results

Iohexol was almost no longer detected in plasma at 24 h that allowed us to extrapolate the area under the curve (AUC) 0–24 h to AUC 0–∞. The dose recovery in urine varied from 60% to 90% of the dose injected. The correlation between urine clearance and iohexol plasma clearance was strong. As expected, a low correlation with the estimated GFR (eGFR) calculated by creatinine-based equations was observed contrary to the Brochner–Mortensen (BM) equation, which exhibited a high correlation.

Research conclusions

This study confirmed the relevance of the plasma clearance of iohexol in the cirrhotic population. It also suggests a high accuracy of the BM equation and confirms the low correlation with eGFR estimated by creatinine-based equations.

Research perspectives

A future study based on a larger cohort of cirrhotic patients with different ascites grades will be performed to devise a PK model allowing the estimation of iohexol plasma clearance from a limited number of samples and to investigate the performance of the BM equation.