Sex Matters to the Success of Organ Transplants

Patients who receive organs from female donors are more likely to reject the transplant and experience higher mortality rates compared to those who receive organs from a male donor, suggest results of a new large study confirming earlier findings from smaller studies. Results of this and other studies also suggest that female transplant patients have a higher rate of rejection compared with their male counterparts.

"This paper, because of the sheer number of transplants studied, shows that sex really does affect the success of a transplant," said Marie L. Foegh, MD, vice president of Female Healthcare at Berlex Laboratories, Inc. in Montville, NJ, "This should have a great impact on the way we practice medicine." The study was published in the October 2002 issue of the Journal of the American Society of Nephrology.

According to Dr. Foegh, based on these and related findings, a transplant patient's gender and the gender of the organ donor should be considered when deciding upon immunosuppressant therapy, drugs that weaken the immune system's ability to react. Immunosuppressants are given to all transplant recipients to reduce the chance their body will reject or attack the transplanted organ. This in turn boosts the chances of a successful transplant.

These results imply that men and women should receive sex-tailored immunosuppression. Currently, experts rely on a person's body weight, not their sex, to calculate the optimal dose of immunosuppressants. "One-size clearly does not fit all," says Dr. Foegh, "These data suggest that men who receive organs from female donors should receive higher doses of immunosuppressants and that women should always be more immunosuppressed than male transplant patients."

With the United States facing a growing shortage of donor organs, finding new ways to further maximize the chance of each transplant success is increasingly important. Currently more than 80,000 Americans are waiting for organ transplants, according to the United Network for Organ Sharing. Only 24,110 transplants were performed in 2001.

New Study Shows Sex Matters to Organ TransplantsDr. Zeier and colleagues at the University of Heidelberg in Germany analyzed a large database involving more than 124,000 kidney transplants, 25,000 heart transplants and 16,000 liver transplants performed around the world. The researchers found that kidneys donated by females fared worse than those from male donors, and this effect was more pronounced among male recipients. For men, the risk of losing a transplanted kidney was 22 percent higher when the kidney came from a female. Women who received a kidney from a female donor were at a 15 percent increased risk of losing the kidney compared to those who received a male-donated organ. Men and women who received female-donated kidneys were also at a slightly yet significantly increased risk of dying compared to those who received a "male organ."

This gender effect was also observed in kidney transplants between siblings who were matched for a group of molecules called the human leukocyte antigens (HLA). HLAs located on the surface of almost all cells are used by the immune system to distinguish between self and non-self. This helps the immune system defend against bacteria, viruses and other unfamiliar cells. HLA-matching improves the success of transplantation by reducing the risk that a recipient's body will attack the transplanted organ. Among HLA-identical siblings, kidneys transplanted from a sister to brother had a significantly higher rate of failure than those transplanted between two brothers.

With respect to heart transplantation, female-donated organs also were more likely to fail, but only among male recipients. Men who received hearts donated by women were 13 percent more likely to lose the heart compared with men who received male-donated organs. While the researchers did not highlight the finding in their paper, their results also show that female heart transplant patients were more likely to reject the organ compared with their male counterparts. Previous studies also support the belief that women organ recipients have a lower rate of success compared with their male counterparts, according to Dr. Foegh.

Study results also suggest the sex of the donor may factor into the success of liver transplantation, although the results were unclear. When the researchers included data from around the world, donor gender did not seem to affect the success of liver transplants. When analyzed by geographical area, however, female-donated livers transplanted to male recipients had significantly reduced risk of success compared with male-donated livers. This sex difference was observed only in North America.

Why the Sex Differences?Just exactly how sex affects the outcome of organ transplants remains a mystery. There are however, a number of theories. In their paper, Dr. Zeier and colleagues suggest that sex differences related to the immune system may be involved. Dr. Foegh also views this as the most plausible explanation.

Numerous studies show that women mount a much stronger immune response than men. Furthermore, Dr. Foegh's own research shows that estrogen influences a part of the immune response important in transplant rejection. Her hypothesis is that a woman's higher estrogen levels make her organs more prone to rejection and at the same time make it more likely that her body will reject an organ transplant.