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Kidney Transplant in End-Stage Renal Disease

Improving Transplant Rates for Successful Outcomes

Jul 17, 2008 Sridhar Nadamuni

Novel therapy improves kidney transplant rates by reducing organ rejection in patients undergoing living- and deceased-donor-kidney transplantation.

Researchers have developed ingenious ways to overcome the risk of organ rejection. According to a study published in the July 17 edition of the New England Journal of Medicine, researchers led by Stanley C. Jordan, M.D., director of the Division of Nephrology and medical director of the Renal Transplant Program at Cedars-Sinai Medical Center (Los Angeles, CA, USA) developed high-dose intravenous immunoglobulin (IVIG) therapy to "desensitize" highly sensitized patients and increase their chances of successful transplantation.

What is Kidney Transplantation?

Kidney transplantation entails surgery to place a healthy kidney in the body. The transplanted kidney takes over the functions of the two kidneys that failed, obviating the need for dialysis.

Although many transplanted kidneys come from dead donors, some come from a living family member. There are long waiting lists for kidney donors. In any case, to avoid rejection of the new kidney by the body, transplant recipients need to take medications for the rest of their lives.

The Cedars-Sinai therapy may be a boon for many patients "sensitized" to transplant antigens (human leukocyte antigens, or HLA) who previously would not have been candidates for transplantation because of their intense immune response to these HLA targets. HLA is a genetic marker located on the surface of the white blood cells. Everyone inherits a set of three antigens from their mother and three from their father. A higher number of matching antigens increases the chance that the kidney will last for a long time.

Prior exposure of the immune system to HLAs either through blood transfusions, previous transplantation or pregnancy, creates antibodies. If a donor organ such as a kidney with the antigens is later transplanted, the antibodies respond, increasing the risk of rejection and loss of the organ.

In fact, each year only 6.5 percent of highly sensitized patients receive a transplant. Most remain on dialysis indefinitely, without hope for a life-saving transplant, with grim financial implications and poor quality of life.

Rituximab and Immune Globulin in Highly Sensitized Patients

The therapy involves a combination of intravenous immunoglobulin (IVIG)(2 g per kilogram on days 0 [the day of infusion] and 30) and rituximab (1 g regardless of weight [or, in children,375 mg per square meter of body-surface area] on days 7 and 22), a monoclonal antibody – an antibody engineered to bind to a specific protein may confer superior benefits to IVIG alone. The transplant rates increased to 80 percent of treated patients. And the one-year patient and graft survival rates were 100 percent and 94 percent, respectively.

Patients who are on dialysis and on the verge of renal failure are candidates for kidney transplant. But if they are at risk of organ rejection due to a sensitized immune system, as indeed one-third of kidney failure patients are, the new therapy is considered ideal.

Breathrough Renal Therapy

In his editorial in the July 17, 2008 edition of The New England Journal of Medicine, Ron Shapiro, M.D., of the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh considers the approach "may represent a breakthrough in the care of sensitized patients awaiting transplantation and may have the potential to help thousands of patients who are languishing on waiting lists around the world." Other methods to decrease patient antibody levels including plasmapheresis, protein A immunoadsorption, intravenous immune globulin,immunosuppression with B-cell–specific agents,or various combinations of these showed only limited success and at substantial expense. They were associated with significant morbidity and death.

Nonetheless, more studies and larger clinical trials are needed before the new therapy is confirmed and established clinically.

The copyright of the article Kidney Transplant in End-Stage Renal Disease in General Medicine is owned by Sridhar Nadamuni. Permission to republish Kidney Transplant in End-Stage Renal Disease in print or online must be granted by the author in writing.

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