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Review
. 2015 Nov;23(Pt B):229-233.
doi: 10.1016/j.ijsu.2015.07.721. Epub 2015 Aug 22.

Current status of pig kidney xenotransplantation

Hayato Iwase  1 , Takaaki Kobayashi  2
Affiliations
Review

Current status of pig kidney xenotransplantation

Hayato Iwase et al. Int J Surg. 2015 Nov.

Abstract

Significant progress in life-supporting kidney xenograft survival in nonhuman primates (NHPs) has been associated largely with the increasing availability of pigs with genetic modifications that protect the pig tissues from the primate immune response and/or correct molecular incompatibilities between pig and primate. Blockade of the CD40/CD154 costimulation pathway with anti-CD154 mAb therapy has contributed to prolongation of kidney xenograft survival, although this agent may not be clinically available. An anti-CD40 mAb-based regimen is proving equally successful, but blockade of the CD28/B7 pathway is inadequate. Severe proteinuria were uniformly documented in the early studies of pig kidney xenotransplantation, but whether this resulted from immune injury or from physiological incompatibilities between the species, or both, remained uncertain. Recent experiments suggest it was related to a continuing immune response. Before 2014, the longest survival of a pig kidney graft in a NHP was 90 days, though graft survival >30 days was unusual. Recently this has been extended to >125 days, without features of a consumptive coagulopathy or a protein-losing nephropathy. In conclusion, overcoming the immune, coagulation, and inflammatory responses by the development of precise genetic modifications in donor pigs, along with effective immunosuppressive and anticoagulant/anti-inflammatory therapy is advancing the field towards clinical trials.

Keywords: Kidney; Nonhuman primate; Pig; Xenotransplantation.

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Conflict of interest statement

Conflict of interest:

none

Figures

Figure 1
Figure 1
Maximum pig kidney graft survival in NHPs (worldwide data)
Figure 2
Figure 2
Mean pig kidney graft survival in NHPs (worldwide data)
See this image and copyright information in PMC

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