History of Kidney Transplantation
Lynn D. Cornell, MD
CHRONOLOGY AND EVOLUTION
First Successful Human Living-Donor Kidney Transplants
1954
Peter Bent Brigham Hospital, Boston, Massachusetts
Transplant donor and recipient were identical twin brothers, one of whom had end-stage renal disease
No immunosuppression necessary in identical twin donor-recipient pairs
Skin autograft and isograft performed on recipient prior to kidney transplant; no evidence of skin rejection
Kidney transplant functioned for 8 years until recipient died of cardiovascular disease
1956
Peter Bent Brigham Hospital, Boston, Massachusetts
1st living-donor kidney transplant performed in a woman; donor was her twin sister
Recipient lived 54 years after receiving kidney transplant
Longest surviving kidney transplant recipient; died of causes unrelated to transplant
1st transplant recipient to become pregnant and give birth
Progress in Immunosuppressive Therapy
Early transplants done in recipients who had undergone total body irradiation
Irradiation allowed for transplantation from nonidentical twin relatives or unrelated donors
While some allografts functioned for years, others failed early post transplant
Late 1950s to early 1960s
High-dose corticosteroids, total body irradiation, graft irradiation
Graft loss due to rejection was common
1963, Murray et al
Prolonged allograft survival with azathioprine (Imuran) immunosuppressive therapy
Acute cellular rejection still common but improved graft survival
1963, Starzl et al
Combined use of azathioprine and prednisone in human kidney transplant recipients reduced rejection
1970 to mid 1980s
Introduction of T-cell depleting agents
Improved prevention and treatment of acute cellular rejection
Minnesota anti-lymphocyte globulin (MALG)
Production shut down in 1992
Anti-thymocyte globulin (Thymoglobulin, Atgam)
OKT3
1979, Calne et al
Use of cyclosporine A (CSA) monotherapy for immunosuppression in kidney allografts
1980, Starzl et al
Combined CSA and prednisone used in deceased-donor kidney transplant recipients
1980 to mid 1990s
Significant improvements in acute rejection rates and long-term graft survival with addition of CSA as maintenance immunosuppression
Mid 1990s to early 2000s
Introduction of oral agents tacrolimus (Prograf) and mycophenolate mofetil (CellCept) as part of maintenance immunosuppression
Intravenous nondepleting T-cell antibodies as induction therapy: Basiliximab (Simulect), daclizumab (Zenapax)
Directed against IL-2 receptor alpha chain (CD25), present on cell surface of activated T cells
Current greatest obstacle in immunosuppression is overcoming antibody response in sensitized patients
Early acute humoral rejection in positive crossmatch (XM) transplants prevented by inhibition of complement component C5
No effective drugs for chronic antibody-mediated rejection
Renal Allograft Pathology
