TY - JOUR
T1 - A Uremic Pig Model for Peritoneal Dialysis
AU - de Vries, Joost C.
AU - van Gelder, Maaike K.
AU - Monninkhof, Anneke S.
AU - Ahmed, Sabbir
AU - Hazenbrink, Diënty H.M.
AU - Nguyen, Tri Q.
AU - de Kort, Gèrard A.P.
AU - Vonken, Evert Jan P.A.
AU - Vaessen, Koen R.D.
AU - Joles, Jaap A.
AU - Verhaar, Marianne C.
AU - Gerritsen, Karin G.F.
N1 - 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.
PY - 2022/9/14
Y1 - 2022/9/14
N2 - 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 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.
AB - 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 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.
KW - animal model
KW - kidney failure
KW - mass transfer area coefficient
KW - peritoneal dialysis
KW - standard peritoneal permeability assessment
KW - Creatinine
KW - Phosphates
KW - Dialysis Solutions
KW - Gentamicins
KW - Uremia/therapy
KW - Urea
KW - Animals
KW - Swine
KW - Peritoneal Dialysis/adverse effects
UR - http://www.scopus.com/inward/record.url?scp=85138458655&partnerID=8YFLogxK
U2 - 10.3390/toxins14090635
DO - 10.3390/toxins14090635
M3 - Article
C2 - 36136573
AN - SCOPUS:85138458655
SN - 2072-6651
VL - 14
JO - Toxins
JF - Toxins
IS - 9
M1 - 635
ER -