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Kidney Week

Abstract: PO0977

A Uremic Pig Model for Peritoneal Dialysis Research

Session Information

  • Peritoneal Dialysis
    November 04, 2021 | Location: On-Demand, Virtual Only
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 702 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

  • de Vries, Joost Christiaan, University Medical Center Utrecht, Utrecht, Netherlands
  • van Gelder, Maaike K., University Medical Center Utrecht, Utrecht, Netherlands
  • Monninkhof, Anneke Suzanne, University Medical Center Utrecht, Utrecht, Netherlands
  • Ahmed, Sabbir, Utrecht University, Utrecht, Netherlands
  • Hazenbrink, Diënty, University Medical Center Utrecht, Utrecht, Netherlands
  • Nguyen, Tri Q., University Medical Center Utrecht, Utrecht, Netherlands
  • Vaessen, Koen, Utrecht University, Utrecht, Netherlands
  • Joles, Jaap A., University Medical Center Utrecht, Utrecht, Netherlands
  • Verhaar, Marianne C., University Medical Center Utrecht, Utrecht, Netherlands
  • Gerritsen, Karin G., University Medical Center Utrecht, Utrecht, Netherlands
Background

The renewed interest in home dialysis requires a translational uremic large animal model to evaluate innovations in peritoneal dialysis. Ideally, toxin plasma levels should be comparable to those in dialysis patients, without requiring maintenance dialysis for survival. To this end, we developed a pig model with stable moderate chronic kidney disease.

Methods

CKD was induced in five female pigs by bilateral subtotal renal artery embolization aiming for embolization of ~85-90% of total kidney tissue. Temporary aggravation of uremia was induced with gentamicin (10 mg/kg twice daily for 7 days). We hypothesized this approach would lead to stable CKD without the need for maintenance dialysis. Peritoneal transport was assessed with a standard peritoneal permeability assessment.

Results

After embolization, urea and creatinine levels increased from 1.6±0.2 to 7.5±1.0 mM and 103±12 to 338±60 µM, respectively, followed by stabilization within 2 weeks to 2.5±1.0 mM and 174±25 µM, respectively. GFR (iohexol clearance) decreased from 49 mL/min to 28 mL/min. Gentamicin induced temporary acute-on-chronic kidney injury with peak urea and creatinine concentrations of 17.0±6.1 mM and 932±504 µM, respectively (Figure 1), while potassium (range 4.1-4.7 mM) and phosphate (range 2.33-2.67 mM) remained stable. Peak indoxyl sulfate and hippuric acid levels were 10.5 ± 0.85 mg/L and 75.3 ± 81.5 mg/L respectively. Peritoneal dialysis, although complicated by peritonitis, could be successfully applied. Peritoneal transport assessment showed a low transport status (D/P creatinine (4h): 0.45±0.12) with an MTAC of 9.6±3.0, 4.6±2.5, 3.4±2.2 mL/min for urea, creatinine, and phosphate respectively.

Conclusion

We have established a pig model with stable moderate CKD without the need for maintenance dialysis. Temporary on-demand acute-on-chronic kidney injury, resulting in uremic solute levels representative for ESKD, allows evaluation of novel dialysis methods.

Figure 1. Urea (left) and creatinine (right) plasma levels after administration of gentamicin (day 0). Mean ± SD, n=10 administrations in n=5 pigs.