Transplantation

Out of turmoil, destruction, and death in World War II came research that led to the artificial kidney and recognition that allograft destruction was an immunological event. Peter Medawar described the accelerated second set rejection of mouse skin grafts while trying to understand why skin allografts always failed on severely burned pilots of the British Royal Air Force. Meanwhile, in Rotterdam, Willem Kolff developed a primitive artificial kidney to treat renal failure that followed severe crush injury during bombing of that city. In the early post-war years, Boston's Peter Bent Brigham Hospital assembled a team, which included Kolff that began human kidney transplantation and refined the artificial kidney. The first kidney transplant at the Brigham, in 1947, came from a cadaver donor and was revascularized by the recipient's antecubital vessels. The graft failed after three days, but it functioned long enough to clear the recipient's uremic coma and permitted recovery from reversible injury to the native kidneys. Next, the team developed the surgical procedure for implanting kidneys in the iliac fossa of dogs and performed it on 15 human recipients between 1949 and 1951. Immunosuppression had not yet arrived and the grafts failed. However, the iliac fossa operation worked well and was extended to kidney transplantation between identical twins in 1954. From 1955 until 1962, cadaver kidneys were transplanted in Paris and Boston with immunosuppression from whole body irradiation and adrenocorti-cal steroids; there were a few hard-earned, short-term successes. The era of pharmacologic immunosuppression began in 1962 with a mother-to-son kidney transplant for which the recipient was treated with both steroids and the antiproliferative drug 6-mercaptopurine. The kidney functioned more than 20 years.

By 2003 three hundred thousand Americans with renal failure were maintained on chronic dialysis; seventeen thousand received kidney transplants in 2002 (8000 from deceased donors and 9000 from living donors). Graft and recipient survival beyond the critical first year exceeds 90 percent in many centers for kidney, pancreas, liver, heart, lung and intestine. At least 100,000 individuals wait for organ transplants in the United States.

Organ Transplantation, 2nd edition, edited by Frank P. Stuart, Michael M. Abecassis and Dixon B. Kaufman. ©2003 Landes Bioscience.

Table 2.1. Immunosuppressive agents

Generic Name

Brand Name

Company

Date of FDA

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