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Gender is an Issue in Kidney Transplantation

LONDON, July 3, 2008--Female recipients of male donor kidneys have a higher rate of graft failure than other combinations of donor and recipient. Consideration of sex should be integrated into future studies and decisions on organ allocation. These are the conclusions of authors of an Article in this week’s edition of The Lancet.

Donor and recipient gender issues are known to be an issue in stem-cell transplants. In such transplants, male recipients of female grafts have an increased risk of graft-versus-host disease and female recipients have an increased risk of rejection of male grafts and of immunogenic reactions against HY—the male Y chromosome-encoded histocompatibility antigen. But the role of these H-Y antigens in kidney transplantation has been disputed.

Professor Alois Gratwohl, University Hospital Basel, Switzerland, and colleagues from the Collaborative Transplant Study in Heidelberg did a retrospective cohort study between 1985 and 2004 in 195 516 recipients from deceased donors at over 400 centres in Europe, aiming to solve this discrepancy between stem cell and solid organ transplants. They used statistical methods capable of assessing multiple variables to compare graft survival and death-censored graft survival rates (ie, excluding deaths from other causes) for female and male donor kidneys in female and male recipients at 1 and 10 years.

The researchers found complex gender interactions in their results. Graft loss was more common with kidneys from female donors than with those from male donors after both 1 and 10 years. Female recipients, by contrast, had a lower rate of graft failure between the end of the first year and the end of the tenth year. Compared with all other combinations of sex, transplantation of male donor kidneys into female recipients was associated with an 8% increased risk of graft failure and an 11% increased risk of death-censored graft failure in the first year. Between years 2 and 10, the corresponding figures were 6% and 10%.

The authors conclude: "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." They elaborate that male recipients could probably profit from bigger male kidneys, with their higher number of nephrons*. Female recipients, however, might not need the same number of nephrons as men, and could profit from the lower likelihood of rejection associated with a sex-matched donor kidney.

In an accompanying Comment, Dr Connie L Davis, Division of Nephrology and Transplantation, University of Washington, Seattle, WA, USA, says: "H-Y antigens can no longer be ignored in Press Telephone: +44 (0)20 7424 4949/4249

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."

Professor Alois Gratwohl, University Hospital Basel, Switzerland. T) + 41 61 265 4254

Comment Dr Connie L Davis, Division of Nephrology and Transplantation, University of Washington, Seattle, WA, USA. T) +1 206-598-6079

Note to Editors

*a nephron is the basic structural and functional unit of the kidney. Its chief function is to regulate the concentration of water and soluble substances like sodium salts by filtering the blood, reabsorbing what is needed and excreting the rest as urine.  
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Posted: July 2008