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Review
. 2022 May;29(3):e12743.
doi: 10.1111/xen.12743. Epub 2022 Mar 16.

Physiological aspects of pig kidney xenotransplantation and implications for management following transplant

Christophe Hansen-Estruch  1 , David K C Cooper  1 , Eric Judd  2
Affiliations
Review

Physiological aspects of pig kidney xenotransplantation and implications for management following transplant

Christophe Hansen-Estruch et al. Xenotransplantation. 2022 May.

Abstract

Successful organ transplantation between species is now possible, using genetic modifications. This article aims to provide a comprehensive overview of the differences and similarities in kidney function between humans, primates, and pigs, in preparation for pig-allograft to human xenotransplantation. The kidney, as the principal defender of body homeostasis, acts as a sensor, effector, and regulator of physiologic feedback systems. Considerations are made for anticipated effects on each system when a pig kidney is placed into a human recipient. Discussion topics include anatomy, global kidney function, sodium and water handling, kidney hormone production and response to circulating hormones, acid-base balance, and calcium and phosphorus handling. Based on available data, pig kidneys are anticipated to be compatible with human physiology, despite a few barriers.

Keywords: kidney; pig; renal function; xenotransplantation.

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Conflict of interest statement

Conflict of interest

None of the authors has a conflict of interest.

Figures

Figure 1:
Figure 1:. Potential Barriers to Pig Kidney Allograft Function
JG, juxtaglomerular; REP, renal epo-producing cell; EPO, erythropoietin; AQ2, aquaporin 2; V2R, vasopressin (V2) receptor; CCD, cortical collecting duct; CSR, calcium-sensing receptor
Figure 2:
Figure 2:. Serum (a) creatinine, (b) albumin, (c) potassium, (d) calcium normalize following renal xenotransplant in a pig-to-baboon model. Hypophosphatemia (e) is also seen following transplant in this model.
These are labeled relative to renal xenotransplantation. Horizontal blue lines represent normal ranges for baboons (Ekser 2012).
Figure 2:
Figure 2:. Serum (a) creatinine, (b) albumin, (c) potassium, (d) calcium normalize following renal xenotransplant in a pig-to-baboon model. Hypophosphatemia (e) is also seen following transplant in this model.
These are labeled relative to renal xenotransplantation. Horizontal blue lines represent normal ranges for baboons (Ekser 2012).
Figure 2:
Figure 2:. Serum (a) creatinine, (b) albumin, (c) potassium, (d) calcium normalize following renal xenotransplant in a pig-to-baboon model. Hypophosphatemia (e) is also seen following transplant in this model.
These are labeled relative to renal xenotransplantation. Horizontal blue lines represent normal ranges for baboons (Ekser 2012).
Figure 3:
Figure 3:. Relative hydrolysis activity of recombinant human renin (a), human kidney renin (b), and porcine kidney renin (c) on angiotensinogen from several different species.
Note that human renin is able to cleave pig angiotensinogen at a low rate but pig renin cleaves human and baboon angiotensinogen at an extremely low rate. This raises the question of whether the RAAS system is preserved following renal xenotransplantation. (Adapted from Evans 1990)
Figure 3:
Figure 3:. Relative hydrolysis activity of recombinant human renin (a), human kidney renin (b), and porcine kidney renin (c) on angiotensinogen from several different species.
Note that human renin is able to cleave pig angiotensinogen at a low rate but pig renin cleaves human and baboon angiotensinogen at an extremely low rate. This raises the question of whether the RAAS system is preserved following renal xenotransplantation. (Adapted from Evans 1990)
See this image and copyright information in PMC

References

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