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NewYork-Presbyterian/Columbia
We are investigating a new immunosuppressant – Rapamune (sirolimus). This anti-rejection medication may enable patients to take lower doses of Neoral (cyclosporine) or Prograf (tacrolimus), the commonly prescribed immunosuppressants, or possibly even eliminate them. This is important because both of these drugs can potentially cause damage to kidneys after prolonged use.
Our physicians also are exploring the viability of using ACE (angiotensin converting enzyme) inhibitors to help heal the transplanted organ and protect it from stress not related to rejection. These drugs, which relax arteries, are now mainly used for blood pressure control and congestive heart failure.
A study currently is monitoring blood levels of cyclosporine to evaluate how to optimize its use.
A successful program was developed for transplant patients who have antibodies against their donors. These patients are treated with plasmapheresis Ü which filters antibodies from blood Ü and intravenous immunoglobulin (IVIG) before and after transplantation. Under special circumstances, a similar treatment may be offered to a recipient who receives an organ from a donor with an incompatible blood type.
A study on tolerance induction is about to begin that will use a biologic agent (thymoglobulin) in the first few days after transplantation along with Rapamycin (sirolumus), to prevent the need for steroids and, eventually, the use of tacrolimus. This treatment may help minimize the side effects of steroids and tacrolimus and permit better long-term function of the new kidneys.
The Immunogenetics Laboratory is conducting extensive clinical monitoring studies of kidney recipients to determine when it may be safe to reduce and discontinue some of the immunosuppressant drugs and to predict rejection before it is significant so treatment can be successful.
The Immunosurgery Basic Science Laboratories are developing new techniques to prevent rejection of the new transplanted kidney by using small molecules (allopeptides), to avoid the use of immunosuppressant agents after the first week of transplantation.
NewYork-Presbyterian/Weill Cornell
The Institute's core research laboratory at NewYork-Presbyterian/Weill Cornell is a national center for investigating the relationship between genes and organ rejection. It analyzes tissue samples sent from about 30 transplant centers throughout the United States for markers of rejection. The laboratory is, for example, researching the genes responsible for the "killer" function of the cells that try to damage transplanted organs.
The Institute has initiated a steroid-free protocol in which patients are given immunosuppressants but never steroids. Part of the standard immunosuppressant therapy over the years has been the inclusion of steroids, which after prolonged use can cause such side effects as weight gain, a "moon face," a worsening of diabetes because of high blood glucose, mood swings, and osteoporosis.
The Institute has recently developed new strategies to reduce the long-term harmful effects of Prograf (tacrolimus) and Neoral (cyclosporine) by significantly reducing the doses needed to protect a patient's new kidney.
One of the new breakthrough techniques developed at the Institute and published last year in New England Journal of Medicine, is the use of a urine test to detect early, subtle signs of transplant rejection so that anti-rejection therapy can be begin as soon as possible. This method avoids the standard method of needle biopsy, in which the surgeon, while guided by ultrasound, passes a thin needle through the patient's skin into the kidney and removes small pieces of the organ.
Plasmapheresis and intravenous immunoglobulin (IVIG) also are being used to expand the possibilities of organ transplanting between blood type ABO incompatible people. Traditionally, a patient with type O blood would only be able to receive a transplant from a type O donor. Using plasmapherisis and IVIG, the researchers are exploring the possibility of removing the antibodies of type O that react against type A so an A donor might be able to give to an O recipient.
The Institute currently is participating in a study in which kidney transplantation is offered to HIV patients on dialysis. These patients may now be considered candidates for transplantation because of advances in medications that control HIV-related infections. The candidates must be relatively healthy with no opportunistic infections, low viral load and an acceptable CD4 count (white blood cells that play an important role in the immune system).
Researchers are investigating new preservation solutions to protect cadaveric kidney cells during the time between when the organ is removed and when it is placed in the recipient. This work is being conducted at the Organ Preservation Laboratory of NewYork-Presbyterian/Weill Cornell. The laboratory serves the New York metropolitan area as its largest organ preservation unit.
