Female Kidney Transplant Recipients Are More Likely To Reject Male Donor Organs

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…Consideration 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 written by 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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Written by: Peter M Crosta

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