Ellegaard_Göttingen_Minipigs_Newsletter 53

Using Göttingen Minipigs as model
for peritoneal dialysis
Anette Blak Gross & Andrew Makin, Citoxlab Denmark, Ejby, Denmark
Peritoneal dialysis is a commonly used treatment in human
patients with severe renal and other diseases. Extended use
of peritoneal dialysis including new peritoneal dialysis formulations
in the pharmaceutical industry requires appropriate
animal models in order to meet the regulatory requirements for
approval of products.
Selection of the correct or most appropriate model depends
on similarities between animals and humans in terms of both
physiology and anatomy. To a degree the relative size of the
animal model can be important. Similar transport properties of
solute and water across the peritoneal membrane in humans
and animals have been important factors in choosing the right
animal model [1] .
Rats, rabbits, and genetically modified mice have been used as
experimental models, but also larger animals such as pigs dogs,
sheep, or even kangaroos have been used [1,2,3] .
The use of each animal model offers advantages and disadvantages
[1] . Rodents are cheap and readily available, but the small
size also complicates catheter insertion and increases the risk
of complications. In addition, the size of the parietal peritoneum
and ratio of peritoneal surface area is different from that of
humans and larger animals. Pigs and other large animal models
also offer the advantage that large volumes of dialysate solution
and human size catheters may be used.
Pigs are an attractive model for peritoneal dialysis due to
similarities in the anatomy and physiology of several of the
abdominal organs and not least the similar size to humans.
In addition, pigs are widely used as a model for many other
procedures involving abdominal tissues and organs (for instance
renal transplantation, intrarenal surgery, artificial bladders and
ureteral stents.
At Citoxlab we have developed an excellent model for peritoneal
dialysis products in the Göttingen Minipig.
The minipigs we have used have been around 4 to 5 months old
and with a weight of ca 10 kg at study initiation. Under general
anaesthesia intraperitoneal catheters are placed and tunnelled
subcutaneously to the neck skin. Dosing is performed once
daily for 10-20 minutes using injection pumps while the animals
are walking freely in their pen unaffected by the dosing as the
catheters are sufficiently long to ensure normal behaviour of
the minipigs.
After some time, typically a few hours, the dialysate (infused
formulation included) can be collected by drainage of the
catheters in conscious animals (typically 75%-100% of infused
formulation can be retrieved). Drainage is preferably achieved
by gravity, and suction only used if necessary. Suitable toxicokinetic/clinical
chemistry/hematology parameters can be
measured in the dialysate after retrieval.
Formulations for intraperitoneal dosing should obviously be
sterile, isotonic, non-irritating and heated to body temperature
before use.
Surgery and handling of catheters are only performed by
dedicated, trained personnel using aseptic procedures at all
time. Care should be taken to ensure that the placement of
the catheter does not compromise the organs and tissues in the
abdomen; irritation could lead to inflammation and peritonitis.
To assist in this, the catheter end is curled, and placement is as
far away from the omentum as possible.
Using these methods, we have successfully achieved dosing
daily for up to 10 days.
When performed correctly, intraperitoneal catheters are very
well tolerated and the Göttingen Minipig is considered a suitable
model for peritoneal dialysis products.
References
1. Animal models in peritoneal dialysis, Olga Nikitidou,Vasiliki
I. Peppa,Konstantinos Leivaditis, Theodoros Eleftheriadis,Sotirios,
G. Zarogiannis, and Vassilios Liakopoulos, Front Physiol.
2015; 6: 244.
2. Swine as Models in Biomedical Research and Toxicology
Testing, M. M Swindle, A. Makin, A. J. Herron, Veterinary
Pathology, 2012: 49 (2): 344.
3. Pawlaczyk K., Baum E., Schwermer K., Hoppe K., Lindholm B.,
Breborowicz A. (2015). Animal models of peritoneal dialysis:
thirty years of our own experience. Biomed. Res. Int. 2015:
Article ID 261813.
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