Solid Organ Transplantation Outcomes

SOLID ORGAN TRANSPLANTATION OUTCOMES

The kidney was the first successfully transplanted human organ. Even when the donor is not an identical twin, patients can do well for some time with grafts from live donors and from unrelated and often totally unmatched cadaveric donors. The half-life of kidney transplants has been increasing and is currently more than ten years. Failures are mainly due to chronic rejection, nephrotoxicity of the calcineu-rin inhibitor agents, and recurrent disease. Liver and heart transplantation have also provided excellent treatment for many patients. The empiric clinical observation is that livers are more tolerogenic than other solid organ allografts, but the basis for this has not been clearly established. The most common indication for liver transplan-tation is now hepatitis C, but this almost invariably recurs in the graft and can lead to liver failure irrespective of rejection and other causes of graft loss. The chief complication of heart allografts is chronic rejection, which involves the coronary arteries with accelerated atherosclerosis. There have now been many cases of bilat-eral lung transplantation with or without the heart; however, the main problem is that the alveoli are particularly susceptible to rejection.

A major conceptual advance in the treatment of diabetes was the successful trans-plantation of islets of Langerhans by a group in Edmonton led by James Shapiro. The early results were excellent using an immu-nosuppressive protocol with no steroids and treating patients suffering from hypo-glycemia. Most patients required two islet cell donors to reach a euglycemic state. At one year, 80 percent of patients no longer required insulin support. This fell to about 75 percent at two years but deteriorated more quickly thereafter. This study was an important proof of principle that islet cell transplantation could achieve good results. Significant obstacles still remain, however, including the exhaustion of transplanted islet cells, control of chronic rejection, balancing the toxicities of immunosup-pressive drugs, and preventing recurrent autoimmune destruction in type I diabetes.

There is continued enthusiasm for the prospect of xenogeneic transplantation of organs and tissues from animals to man, but to date there have been no long-term successes. The best result occurred in the 1960s, when Reemtsma transplanted a kidney from a chimpanzee to a patient who achieved adequate graft function for nearly ten months. There are many difficulties, however, with xenografting. In addition to hyperacute rejection, accel-erated rejection, and other immunological factors, there are physiological consider-ations regarding organ size disparities and whether xenogeneic proteins will function satisfactorily in man.