A Uremic Pig Model for Peritoneal Dialysis

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 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.

Renal Embolization-Induced Uremic Swine Model for Assessment of Next-Generation Implantable Hemodialyzers

“…Importantly, this approach preserves the retroperitoneal anatomic planes and vasculature, facilitating straightforward exposure of the iliac vasculature for anastomosis of the SNMHD or other implantable, blood-based renal replacement technologies. Compared to the approaches described by de Vries [22] and Misra [24], our approach offers at least two distinct advantages. First, both groups reported fatal or euthanasia-requiring complications associated with their single-stage embolization procedures.…”

“…Misra and colleagues found that single-stage bilateral endovascular nephrectomy can produce mobility-limiting pain and an overwhelming inflammatory response that is life-threatening for the animal [ 24 ]. Recently, a similar endovascular nephrectomy protocol has been used to induce uremia in swine for the study of novel peritoneal dialysis therapies [ 22 ]. The same group has also developed an acute-on-chronic goat model of kidney injury using a combination of endovascular nephrectomy and gentamicin-induced kidney injury with animals surviving for 10 months; a procedure which may be advantageous for studying chronic dialysis therapies [ 23 ].…”

“…Compared to the approaches described by de Vries [ 22 ] and Misra [ 24 ], our approach offers at least two distinct advantages. First, both groups reported fatal or euthanasia-requiring complications associated with their single-stage embolization procedures.…”

“…An ideal model should replicate human renal physiology and anatomy, induce stable renal failure while remaining compatible with standard hemodialysis techniques, and preserve surgical anatomy for implantation of experimental RRT devices. Animal models with some of these characteristics have been established in swine, sheep, and goats [ 21 , 22 , 23 , 24 ]. Specifically in swine, several models have been developed to induce acute and chronic renal failure via surgery, ischemia-reperfusion (IR) injury, sepsis, nephrotoxic drugs, and combinations these modalities.…”

“…Sepsis-induced renal injury, while effective at inducing renal injury, creates multi-organ system dysfunction that would compromise downstream evaluation of novel RRT [ 30 ]. Finally, drug-induced renal injury has been combined with surgical nephrectomy to induce acute-on-chronic renal injury to study reno-protective drug therapies as well at RRT [ 22 , 31 , 32 ]. Swine subtotal endovascular nephrectomy, originally described by Misra and colleagues, effectively and reproducibly induces chronic renal failure and leaves retroperitoneal anatomy intact for subsequent device implants [ 24 ].…”