title: Renal xenotransplantation: experimental progress and clinical prospects.
abstract: There are >100,000 patients waiting for kidney transplants in the United States and a vast need worldwide. Xenotransplantation, in the form of the transplantation of kidneys from genetically engineered pigs, offers the possibility of overcoming the chronic shortage of deceased and living human donors. These genetic manipulations can take the form of (i) knockout of pig genes that are responsible for the expression of antigens against which the primate (human or nonhuman primate) has natural "preformed" antibodies that bind and initiate complement-mediated destruction or (ii) the insertion of human transgenes that provide protection against the human complement, coagulation, or inflammatory responses. Between 1989 and 2015, pig kidney graft survival in nonhuman primates increased from 23 days to almost 10 months. There appear to be no clinically significant physiological incompatibilities in renal function between pigs and primates. The organ-source pigs will be housed in a biosecure environment, and thus the risk of transferring an exogenous potentially pathogenic microorganism will be less than that after allotransplantation. Although the risk associated with porcine endogenous retroviruses is considered small, techniques are now available whereby they could potentially be excluded from the pig. The US Food and Drug Administration suggests that xenotransplantation should be restricted to "patients with serious or life-threatening diseases for whom adequately safe and effective alternative therapies are not available." These might include those with (i) a high degree of allosensitization to human leukocyte antigens or (ii) rapid recurrence of primary disease in previous allografts. The potential psychosocial, regulatory, and legal aspects of clinical xenotransplantation are briefly discussed.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Wijkstrom
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Hayato
authors.initials: H
authors.lastname: Iwase
authors.affiliation: School of Social Work, Abilene Christian University, Abilene, Texas, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Paris
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address: cooperdk@upmc.edu.
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D064593:Heterografts; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects / Q000266:history / Q000379:methods*; D010641:Phenotype; D012307:Risk Factors; D013045:Species Specificity; D034421:Sus scrofa / Q000235:genetics* / Q000276:immunology; D014019:Tissue Donors / Q000600:supply & distribution; D023001:Transplantation Tolerance; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000266:history; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents
keywords: allosensitization; clinical trial; genetically engineered xenotransplantation; kidney; pig