A Uremic Pig Model for Peritoneal Dialysis
de Vries, Joost C.; van Gelder, Maaike K.; Monninkhof, Anneke S.; Ahmed, Sabbir; Hazenbrink, Diënty H.M.; Nguyen, Tri Q.; de Kort, Gèrard A.P.; Vonken, Evert Jan P.A.; Vaessen, Koen R.D.; Joles, Jaap A.; Verhaar, Marianne C.; Gerritsen, Karin G.F.
(2022) Toxins, volume 14, issue 9
(Article)
Abstract
With increasing interest in home dialysis, there is a need for a translational uremic large animal model to evaluate technical innovations in peritoneal dialysis (PD). To this end, we developed a porcine model with kidney failure. Stable chronic kidney injury was induced by bilateral subtotal renal artery embolization. Before applying
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PD, temporary aggravation of uremia was induced by administration of gentamicin (10 mg/kg i.v. twice daily for 7 days), to obtain uremic solute levels within the range of those of dialysis patients. Peritoneal transport was assessed using a standard peritoneal permeability assessment (SPA). After embolization, urea and creatinine concentrations transiently increased from 1.6 ± 0.3 to 7.5 ± 1.2 mM and from 103 ± 14 to 338 ± 67 µM, respectively, followed by stabilization within 1–2 weeks to 2.5 ± 1.1 mM and 174 ± 28 µM, respectively. Gentamicin induced temporary acute-on-chronic kidney injury with peak urea and creatinine concentrations of 16.7 ± 5.3 mM and 932 ± 470 µM respectively. PD was successfully applied, although frequently complicated by peritonitis. SPA showed a low transport status (D/P creatinine at 4 h of 0.41 (0.36–0.53)) with a mass transfer area coefficient of 9.6 ± 3.1, 4.6 ± 2.6, 3.4 ± 2.3 mL/min for urea, creatinine, and phosphate respectively. In conclusion, this porcine model with on-demand aggravation of uremia is suitable for PD albeit with peritoneal transport characterized by a low transport status.
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Keywords: animal model, kidney failure, mass transfer area coefficient, peritoneal dialysis, standard peritoneal permeability assessment, Creatinine, Phosphates, Dialysis Solutions, Gentamicins, Uremia/therapy, Urea, Animals, Swine, Peritoneal Dialysis/adverse effects, Health, Toxicology and Mutagenesis, Toxicology, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 2072-6651
Publisher: Multidisciplinary Digital Publishing Institute
Note: Funding Information: This study was supported by the Dutch Kidney Foundation and Dutch Ministry of Economic Affairs by means of a PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public private partnerships (DKF project code PPS08). In addition, this study was supported by the European Union Horizon 2020 research and innovation program, grant agreement no. 945207. Furthermore, a part of this project was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 813839. Publisher Copyright: © 2022 by the authors.
(Peer reviewed)