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Graft-Success Risk Higher for a Woman Getting Male Kidney 7-7-08

BASEL, Switzerland, July 7 -- Male-to-female kidney transplants may reduce graft-success rates, possibly because of minor histocompatibility antigens encoded by genes on the Y chromosome, a large retrospective study found.

Kidneys from male donors transplanted to female recipients had the highest risk of graft failure during the first year (hazard ratio 1.08, P=0.003) and from two to 10 years (HR 1.06, P=0.008) compared with all other gender combinations, reported Alois Gratwohl, M.D., of the University Hospital Basel here, and colleagues in the July 5 issue of The Lancet.

However, because the retrospective study of almost 200,000 grafts found only a small increase in risk, the findings shouldn't impact practice at this point, commented Connie L. Davis, M.D., of the University of Washington in Seattle, in an accompanying editorial.

Much needs to be done on the actual antigens and the immunological responses that might be associated with rejection, she said, but Y-chromosome encoded minor histocompatibility antigens (H-Y antigens) appear to be at play.

"The science is still too premature to suggest that allocation schemes from dead donors or selection of living donors for transplantation take notice of this effect," she said, "in view of the good long-term success with sex-mismatched allografts and the limited access to organs."

H-Y antigens have been known to play a role in hematopoietic stem cell transplant success, but their role in solid tumors has been debated.

The reason for the late recognition of this effect in clinical kidney transplantation could have been because donor and recipient sex have independent and opposing effects, Dr. Gratwohl and colleagues said.

The researchers retrospectively analyzed data on 195,516 consecutive kidney transplants from deceased donors done between 1985 and 2004 at 400 transplant centers in 45 countries participating in a collaborative transplant study.

During a mean follow-up of 5.6 years after transplantation, 40% of the grafts failed. At 10 years, 20% patients had a functioning graft.

When comparing genders in the univariate analysis, the researchers found lower one-year graft survival rates for kidneys from female donors than for those from male donors irrespective of the sex of the recipients (HR 1.14, P<0.001).

However, the highest failure rate was seen in male kidney grafts in female recipients (HR 1.08, P=0.003).

In multivariate analysis, transplantations of kidneys from men to women had a likewise increased risk of graft failure compared with other gender combinations (HR 1.06, P=0.008).

"The survival advantage of the kidneys from male donors in male recipients is offset by the H-Y effect in female recipients," the researchers said.

The H-Y effect of a female recipient and male donor compared with other gender combinations was significant both early and late post-transplantation.

For graft survival, the hazard ratio was 1.08 in the first year (P=0.003) and 1.06 from year two through 10 years (P=0.008). For death-censored graft survival, the hazard ratios were 1.11 (P=0.003) and 1.10 (P<0.001), respectively.

Dr. Gratwohl's group concluded that adding gender combinations to considerations used for allocation of kidneys would probably benefit both men and women because men would get higher nephron doses from male donors and women would have a lower likelihood of rejection with a sex-matched donor kidney.

But, "this would limit women's access to transplant even further," Dr. Davis said. "Women already have somewhat of a decreased access because they are more often times sensitized because they have had pregnancy."

The scientific proof isn't strong enough yet, she emphasized, although "H-Y antigens can no longer be ignored in the setting of solid-organ transplantation."