New research published in The Lancet suggests that sex-matching kidney donors and recipients may result in better outcomes. The report finds that when females receive a male donor kidney, they have higher rates of graft failure compared to the other three combinations of donor and recipient. These findings imply that future studies and decisions about organ donations should take sex into consideration.

This is not the first time that sex issues have come up in donor-recipient relationships. For example, in stem-cell transplants, males who receive female grafts are more likely to develop graft-versus-host disease, and females who receive male grafts have an increased risk of rejection and immunogenic reactions against H-Y (the male Y chromosome-encoded histocompatibility antigen). However, how H-Y antigens affect the results of kidney transplants is still being debated.

This most recent research comes from a retrospective cohort study conducted by Professor Alois Gratwohl (University Hospital Basel, Switzerland) and colleagues from the Collaborative Transplant Study in Heidelberg. They studied 195,516 people who received kidney from deceased donors between 1985 and 2004 at over 400 centers in Europe. To investigate the gender differences between stem cell and solid organ transplants, the researchers employed multivariate statistical methods. The models allowed researchers to compare rates of graft survival and death-censored graft survival at 1 and 10 years for female and male recipients who received female and male donor kidneys. Death-censored graft survival is a measure that excludes deaths from causes not related to graft failure.

The results of the study included interesting gender interactions. After 1 and 10 years, recipients of female kidneys were more likely to experience graft loss than recipients of male kidneys. In general, female recipients were less likely to experience graft failure between years 1 and 10 compared to male recipients. However, when male kidneys were donated to female recipients, there was an 8% increase in graft failure risk and an 11% increase in death-censored graft failure risk in the first year compared to the other three combinations of donor and recipient sex. These risks changed to 6% and 10%, respectively, between years 2 and 10.

"Our multivariable analysis showed that transplantation of kidneys from male donor into female recipients caused an increased rate of graft failure, which suggests an immunological H-Y effect in renal transplantation during the first year after transplantation that extends to 10 years of follow-up..nsideration of sex should be integrated into future prospective analyses and decisions on organ allocation," conclude the authors. They also speculate that since male kidneys are larger and have a higher number of nephrons (the basic structural and functional unit of the kidneys), they may be a better match for male recipients. Women, on the other hand, may not need as many nephrons, and could benefit from the less-risky female donor kidney.

Accompanying this article is a Comment Dr Connie L Davis (Division of Nephrology and Transplantation, University of Washington, Seattle, WA, USA). She writes: "H-Y antigens can no longer be ignored in the setting of solid-organ transplantation. A lot of work still needs to be done on the actual antigens and the immunological responses that might be associated with rejection. However, 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, in view of the good long-term success with sex-mismatched allografts and the limited access to organs."

H-Y as a minor histocompatibility antigen in kidney transplantation: a retrospective cohort study
Alois Gratwohl, Bernd Döhler, Martin Stern, Gerhard Opelz
The Lancet (2008). 372(9632): pp. 49-53.
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: Peter M Crosta

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