Vall d'Hebron has studied how the sex of the donor and the recipient influence survival after transplantation

The Vall d'Hebron University Hospital has conducted the first systematic review to assess how being a man or a woman influences solid organ transplant operations. The aim of the research team was to find out whether the sex of the patient affected his or her post-surgery evolution. In total, the study published to the European Journal of Internal Medicine was able to identify 1,103 studies published between 2016 and 2021, of which only 22 had sex-segregated data. This shows that sex is a variable that is not normally taken into account in transplantation studies. The research team analyzed the 22 selected scientific studies that contained data from 1,045,380 patients.

Women have lower mortality rate after kidney or liver transplantation

The group of researchers from five countries, led by Professor Jordi Rello, head of the Innovation in Pneumonia and Sepsis group at the Vall d'Hebron Research Institute (VHIR) and Node 18 of the Center for Biomedical Research Network on Respiratory Diseases (CIBERES) and Professor of Medicine at the International University of Catalonia, was able to draw a number of relevant conclusions. The first is that more than double solid-organ transplants are performed in men than in women (63.7% versus 36.3%).

Regarding survival, women have lower mortality, by three percentage points, after kidney and/or liver transplantations. In heart transplants, there were no differences between the two sexes, whereas in lung transplants there was insufficient data to draw definitive conclusions. On the other hand, men had a lower rate of readmission for postoperative complications in all types of transplants.

The oncologic risk of people who had received a transplant was also analyzed. Although the differences in incidence were not significant, discrepancies in the types of cancer observed were observed. Women were more at risk for Kaposi's sarcoma, gynecological or pulmonary tumors, while men were more likely to develop kidney or bladder cancer.

According to Teresa Pont, coordinator of Transplantations at Vall d'Hebron University Hospital, principal investigator VHIR's group Donation and Transplantation of Organs, Tissues and Cells and one of the authors of the study: "The differences recorded should make us think about whether we are making an adequate approach or whether we should include more parameters in our studies". She adds that "when the breakdown by sex is not taken into account, vital information is lost in order to know the particularities of the patient's situation, whether male or female".

Having segregated information is the first step in rethinking why and how gender biases can affect certain diseases. It should be remembered that a bias is a distortion resulting from an inadequate estimation of facts or data that is often deeply rooted and difficult to recognize. Therefore, it can distort the entire healthcare process, both in diagnosis (access, delay, and unequal waiting time, to adequate healthcare from the onset of symptoms, diagnostic errors...) and the derived effort (type of therapeutic strategies, consumption and expenditure by sex, and over-prescription of therapies, etc.). The only defence against a bias is high-quality data that show beyond any doubt where the error of perception that has caused it exists.

Sex is a variable that has long been ignored by medical research. The paradigmatic example is that, for decades, women were not included in clinical trials, since it was considered that their hormonal variations invalidated the results.

The importance of taking into account the biological sex of the donor

When analyzing the percentages of rejection of the new organ, whether total or partial, it is necessary to take into consideration not only the sex of the recipient but also that of the donor. A variable that is almost never taken into account. The results showed that in the case of kidney transplants, if the donor is male and the recipient is female, the percentage of graft failure is higher in the latter, regardless of age. However, when the donor is female, female recipients over 45 years of age have less rejection than male recipients of any age.

According to Prof. Rello, "sex hormones are regulated by the sex chromosomes and influence the intensity of the inflammatory response, which affects infections and the risk of rejection, depending on whether you are male or female (and your age)". Consequently, he suggests that "it is important for professionals to consider these variables when deciding on the treatment strategy post-transplant, and that new specific studies should be conducted to be able to decipher the complex interaction of these factors and how they influence the acceptance or not of the new organ". Dr. Rello affirms that "the hope of the researchers is to contribute to improving the survival and quality of life of the patients, providing knowledge to optimize transplants and to continue advancing towards personalized treatments".

As this is the first meta-analysis of this type, the results are partial, for example, it is certain that some of the conclusions of the study can be attributed to biological differences, but not all; others are the result of social and cultural differences between the genders in our society. For example, some studies have pointed out that men statistically have a more irregular pattern of taking post-kidney transplant medication. This finding, which seems to be solidly due to social factors, may be one of the causes of the higher mortality of the male sex after this intervention.

The research team hopes that their results will be useful for further studies to add sex and gender among the variables to be taken into account in order to better understand how they influence the survival and quality of life of transplanted women and men.