Plasma iohexol clearance (CLiohexol) is a reference technique for glomerular filtration rate (GFR) determination. In routine practice, CLiohexol is calculated using one of several formulas, which have never been evaluated in kidney transplant recipients. We aimed to model iohexol pharmacokinetics in this population, evaluate the predictive performance of three simplified formulas and evaluate whether a Bayesian algorithm improves CLiohexol estimation.
After administration of iohexol, six blood samples were drawn from 151 patients at various time points. The dataset was split into two groups, one to develop the population pharmacokinetic (POPPK) model (n = 103) and the other (n = 48) to estimate the predictive performances of the various GFR estimation methods. GFR reference values (GFRref) in the validation dataset were obtained by non-compartmental pharmacokinetic (PK) analysis. Predictive performances of each method were evaluated in terms of bias (ME), imprecision (root mean square error [RMSE]) and number of predictions out of the ±10% or 15% error interval around the GFRref.
A two-compartment model best fitted the data. The Bayesian estimator with samples drawn at 30, 120 and 270 min allowed accurate prediction of GFRref (ME = 0.47%, RMSE = 3.42%), as did the Brøchner-Mortensen (BM) formula (ME = − 0.0425%, RMSE = 3.40%). With both methods, none of the CL estimates were outside the ±15% interval and only 2.4% were outside the ±10% for the BM formula (and none for the Bayesian estimator). In patients with GFR ≤30 mL/min/1.73 m2, the BM formula performed very well, while the Bayesian method could not be evaluated in depth due to too small a number of patients with adequate sampling times.
GFR can be estimated with acceptable accuracy in kidney transplant patients using the BM formula, but also using a Bayesian algorithm.
The authors would like to acknowledge the patients who participated in this study, as well as the investigators and on-site staff who made this study possible. We warmly thank Prof. Pierre Marquet for his careful reading of this paper and Karen Poole for correcting our English.
Author contributions: Joevin Besombes/Camille Riff: acquisition of data, analysis and interpretation; writing, review and/or revision of the manuscript. Hélène Blasco: conception and design; writing, review and/or revision of the manuscript. Philippe Gatault: conception and design; acquisition of data, review and/or revision of the manuscript. Christelle Barbet: acquisition of data, review and/or revision of the manuscript. Matthias Büchler: conception and design; acquisition of data, review and/or revision of the manuscript. Jean-Michel Halimi: conception and design; acquisition of data, review and/or revision of the manuscript. Chantal Barin-Le Guellec: conception and design; analysis and interpretation; writing; study supervision; review and/or revision of the manuscript. Isabelle Benz-de Bretagne: conception and design; acquisition of data, analysis and interpretation; writing, review and/or revision of the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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