The New Kidneys

When 1,200 medical researchers assembled at Manhattan's Waldorf-Astoria hotel last week for the Sixth International Congress of the Transplantation Society, some of the loudest applause was given not to a physician but to a philosophy professor from Indianapolis. In 1959 the man, John Riteris, now in his early 40s, was stricken by severe kidney disease. Faced with the prospect of imminent death--or dismal years on a kidney machine--he agreed to what was then still a highly experimental treatment: replacement of his dying kidneys with one donated by his twin brother. Now, 17 years later, John Riteris is one of the longest survivors of what is a major unsung success story of contemporary medicine: kidney transplants.

Though heart transplants have been more often in the headlines, the results with kidneys have been far more enduring. Of some 25,000 known kidney transplants performed in the past two decades, nearly half of the recipients are still alive today. In contrast, of the 316 heart transplants that have been performed since the first successful operation in 1967, only 63 patients survive.

The kidney transplanters owe much of their success to a rapidly emerging science: immunology. Its practitioners devote themselves to the extremely complex task of finding ways of overcoming the body's natural defenses against foreign cells, so that transplanted tissue will not be rejected. Up to now, the usual tactic has been a form of biochemical overkill known as immunosuppression: the transplant patient is heavily dosed with drugs that interfere with the function of white blood cells--the major weapon of the immune system--and block the formation of antibodies. These are the wondrous proteins designed by nature to seek out invading cells, including transplant tissue, and set the stage for their destruction by the white cells. At best, though, immunosuppression is a blunderbuss approach that also leaves the body unshielded against lethal germs and sometimes apparently cancer.

As a result, researchers are stepping up the hunt for a better way. One of these is Surgeon-Immunologist Felix Rapaport of the New York University Medical Center, who became the Transplantation Society's new president-elect last week. Prior to implanting new kidneys in beagles, he has been removing some of their bone marrow--the site, along with the lymph nodes, of white-blood-cell production--and irradiating the dogs. The X rays destroy the ability of the remaining bone marrow and lymphoid tissue to produce white blood cells. Then he reinjects the marrow cells, thus restoring the animal's immune system, and quickly performs the transplant. Some of the beagles on which this technique has been tried have already survived for three years, without needing any immunosuppressive drugs.

Rapaport notes that some of the early kidney transplant recipients, including Riteris, were in fact also irradiated. But in most cases the technique proved unreliable--in part because of uncertainties about how much X-ray dosage the body could withstand--and was thus abandoned. Rapaport believes, however, that his dog experiments now indicate that these problems could be solved, and that irradiation, plus bone-marrow reconstitution, may eventually offer a way of eliminating troublesome immunosuppressive drug therapy in human transplant recipients as well.

Another promising approach was reported by Dr. Robert R. Riggio and his co-workers at New York Hospital-Cornell Medical Center. Riggio was aware that women produce large amounts of antibodies during pregnancy, specifically in response to the fetus, yet somehow manage to tolerate this "foreign" tissue in their bodies. He therefore wondered whether the baby might actually be stimulating the production of "blocking antibodies" within the mother that neutralize her immune reaction against the fetus. If so, perhaps the same response could be artificially produced in transplant recipients.

To test his theory, Riggio has been injecting gamma globulin from human placentas, which are usually discarded after delivery, into patients at the hospital's Rogosin Kidney Center. He hopes that the placental extract will transfer blocking antibodies into them. That then might encourage acceptance of new organs. A positive sign: when Riggio examined long-term transplant survivors at the center, he found that their acceptance of kidney grafts somehow appeared to have been enhanced by a biochemical mechanism similar to that postulated in pregnant women.

Neither Rapaport nor Riggio can yet fully explain such effects, but they think that in successful transplants there apparently has been a tilt in the balance of immune cells toward those that tolerate specific foreign tissue rather than reject it. In short, the immunological blunderbuss can be replaced by a more accurate biochemical rifle.

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