![]() Intermittent hypovolemia has been noted among NHP xenograft recipients, although oral intake was not increased in a compensatory manner ( 9). Pig xenografts may be incompatible with other aspects of human renal physiology. ![]() Although a high degree of homology has been noted between human and pig erythropoietin ( 10), incompatibility could be managed with recombinant human erythropoietin, a common practice for anemia among patients with chronic kidney disease. This may be secondary to immunosuppression, blood draws, or incompatibility of NHP and pig erythropoietin ( 9, 10). Additionally, anemia among NHP recipients has been reported ( 9). ![]() Similar to allotransplantation, this could be managed with increased non-dairy dietary intake and oral phosphorus supplementation. Although most serum electrolyte concentrations remained within normal human limits in NHP recipients, gradual and mild hypercalcemia and late hypophosphatemia have occurred ( 9). Second, xenotransplants may enhance uric acid elimination, as they filter as well as secrete uric acid, perhaps protecting recipients from posttransplant gout ( 9).Īlthough pig-to-NHP models suggest that some aspects of renal xenograft physiology may differ from the human kidney, these differences may be successfully managed. Assuming immune-mediated rejection is prevented, these data suggest glomerular filtration should occur normally in living humans ( 8). Serum creatinine remained within normal human ranges, and proteinuria has not been observed in recent pig-to-NHP experiments ( 9, 10). First, renal blood flow and glomerular filtration rate are similar in pigs and humans (human, 4 mL/min/g vs. There are several aspects of renal physiology likely to be normal in human xenotransplant recipients. ( 9), can be leveraged to hypothesize which kidney functions may be normal or altered in living human xenotransplant recipients ( 10). Although phase 1 clinical trials are needed, the physiologic findings from pig-to-NHP models, as previously reviewed by Iwase et al. Given the complex, systemic functions performed by the human kidney, including filtration, electrolyte balance, volume status, blood pressure, and stimulation of erythropoiesis, xenograft physiologic compatibility requires evaluation ( Figure 1). Notably, although the kidneys made urine, they did not clear creatinine. Given the physiologic derangements of the brain-dead recipient ( 8), however, this pre-clinical model was not designed to assess xenotransplant physiologic function. Third, no porcine endogenous retrovirus transmission was observed. Second, relative hemodynamic stability was maintained intraoperatively, and vascular anastomotic integrity was maintained at the higher human blood pressures. First, no hyper-acute rejection occurred, consistent with the negative pre-transplant pig-to-human crossmatch. The pig-to-decedent, or Parsons, model demonstrated important safety and feasibility features of kidney xenotransplantation ( 5). The development of novel gene-editing technology to “humanize” the pig organ, however, has enabled successful pig-to-non-human primate (NHP) models and a return to animal-to-human experimentation ( 5– 7). The primary limitation of using pigs for xenotransplantation was the cross-species immunologic barrier ( 2, 4). Pigs have organs comparable in size and function with humans and lower risk of zoonoses, and their hormones and tissues are already used, suggesting positive public opinion ( 2, 3). Pigs soon became the ideal organ source because they produce large litters and mature rapidly, and availability is virtually unlimited ( 2, 3). Although the recipient survived 9 months, subsequent animal-to-human transplants were limited by immunologic barriers and the need for a sustainable organ source ( 2). In 1964, the first kidney xenotransplant from a chimpanzee to human was performed successfully ( 1).
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