Remaining Physiological Barriers in Porcine Kidney Xenotransplantation: Potential Pathways behind Proteinuria as well as Factors Related to Growth Discrepancies following Pig-to-Kidney Xenotransplantation

Considerable shortages in the supply of available organs continue to plague the field of solid organ transplantation. Despite changes in allocation, as well as the utilization of extended criteria and living donors, the number of patients waiting for organs continues to grow at an alarming pace. Xenotransplantation, cross-species solid organ transplantation, offers one potential solution to this dilemma. Previous extensive research dedicated to this field has allowed for resolution of xenograft failure due to acute rejection, leaving new areas of unresolved challenges as barriers to success in large animal models. Specific to kidney xenotransplantation, recent data seems to indicate that graft compromise can occur due to discrepancies in growth between breeds of donors and significant proteinuria leading to nephrotic syndrome in the recipient. Given these potential limitations, herein, we review potential pathways behind proteinuria, as well as potential causative factors related to growth discrepancies. Control of both of these has the potential to allow xenotransplantation to become clinically applicable in an effort to resolve this organ shortage crisis

High risk, high reward: An analysis of outcomes for candidates awaiting hepatic re-transplantation

Background. Liver re-transplantation (re-OLT) remains the only feasible option for patients with graft failure following liver transplantation. Sparse resources and a growing waitlist mandate that available grafts are allocated properly. We studied the differences in patient demographics, characteristics, and survival for those listed for re-OLT in a region with prolonged wait times.Material and methods. We performed a single-center retrospective study, from 2005 to 2013, of adult candidates listed for liver re-OLT at a tertiary care center within United Network for Organ Sharing (UNOS) region 1.Results. Of the 48 patients listed for re-OLT, 1(2%) improved while waiting, 14(29%) died while waiting, and 33(69%) underwent re-OLT. Those re-transplanted represented 11% of the center’s adult liver transplant volume during the same time period. Comparing those who died while waiting to those who achieved re-OLT, there was no significant difference in age (median 52 vs. 48 years, p=0.56) or MELD at second listing (median 29 vs. 26, p = 0.90). Waitlisted candidates who failed to achieve re-transplant died on average of 15.5 days (IQR 36 days) days after re-listing. Those re-transplanted achieved 3-year survival of 70% and there was no significant difference in 3-year survival of those re-transplanted within or beyond 90 days of first transplant (70% vs. 69.5%, p = 0.28).Conclusions. In conclusion, re-OLT is the only viable option for candidates with nonreversible liver graft failure. Inability to achieve re-OLT leads to nearly assured and expeditious death. Despite technical challenges, in experienced hands excellent long term survival following re-OLT can be achieved

Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model.

The liver's regenerative capacity is unique, but too small a segment can overwhelm its ability to simultaneously regenerate and support the host, resulting in liver dysfunction and death. Here we tested a temporary Xenogeneic Heterotopic Auxiliary Liver Transplant (XHALT) from Gal-KO miniature swine in a baboon model of Post-Hepatectomy Liver Failure (PHLF) by 90%- hepatectomy. Immunosuppression consisted of CVF, ATG, FK 506 and steroids. 90%-hepatectomized animals died within 4-5 days with the clinical picture of PHLF, (high LFTs and bilirubin, ascites, encephalopathy and coagulopathy). The 10% remnants had macroscopic and histological evidence of severe steatosis and absence of hepatocyte replication. In contrast, the addition of XHALT prolonged survival up to 11 days, with the cause of death being sepsis, rather than liver failure. The remnant liver appeared grossly normal, and on histology, there was no evidence of fatty infiltration, but there was pronounced Ki-67 staining. In conclusion, temporary auxiliary xenografts have the potential to support a small for size liver graft while it grows to adequate size or provide an opportunity for organ recovery in acute liver failure