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Acknowledging Disparities Between Sexes in Kidney Transplantation this World Kidney Day

There are approximately 170,000 patients in the US and Europe waiting for a kidney transplant (1). Sadly, some of them face a long, sometimes indefinite, time on transplant waiting lists without receiving a potentially life-saving kidney transplant. Furthermore, recent data shows that, compared to men*, women* are less likely to be waitlisted for a kidney transplant and to find a compatible donor organ. Once listed, factors, including pregnancy-induced human leukocyte antigen (HLA) sensitization, can result in women facing longer waiting times than men (2).

Chronic kidney disease (CKD) is a progressive condition characterized by the gradual loss of kidney function over time (3). When kidneys cease to work, kidney transplantation becomes a lifesaving or life-altering option. However, access to transplantation is not always equitable (2).
To recognize this year’s theme of World Kidney Day, “Kidney health for all – preparing for the unexpected, supporting the vulnerable”, we are putting a focus on the importance of improving equity in access to transplant, and particularly of recognizing disparities between sexes in kidney transplantation and the contributing factors that surround the issue.

Ensuring more equitable patient care in kidney transplantation is a priority for Hansa and one that we believe will help deliver better patient outcomes. To bring an expert perspective to this topic, we spoke with Dr Siân Griffin, Consultant Nephrologist and Honorary Professor at Cardiff University, who is responsible for the care of patients with progressive kidney disease prior to needing dialysis or a transplant, as well as potential living donors for their assessment prior to donation. Together, we discussed both her passion and expertise in improving transplant opportunities for patients who are highly sensitized, and more specifically, her thoughts and experiences on the distinct medical and societal factors that may impact rates of kidney transplantation, particularly those that may lead to greater disparity between sexes.

Q1 What does current data tell us about disparities between sexes in the journey to transplantation?

Recently, we have seen a wealth of data from several different countries and healthcare systems signaling the role that disparities between sexes play in the journey of a patient who needs a kidney transplant. Research shows that compared to men, women are less likely to be referred for a kidney transplant, less likely to appear on a waiting list and less likely to undergo a transplant (4).

There are several factors that may potentially lead to this disparity and subsequently disadvantage women, including medical, financial and societal. However, I believe that HLA sensitization is the most significant factor leading to this disparity in access to kidney transplant, with research showing that women were incompatible with at least one living donor three times more frequently than men (2). Sensitization can arise following a blood transfusion, a previous transplant, or pregnancy, meaning that women are particularly vulnerable to higher sensitization rates (2).

We know that progression of CKD is slower in women, and one would expect the rates of pre-emptive transplantation (transplantations performed before starting dialysis) to be greater, as there is more time to complete the donor and recipient evaluations. In reality, men are more likely to receive a pre-emptive transplant. One factor that might play into this disparity is the fact that women are more likely to be sensitized against their partner or spouse if they have had children together (2).

Q2 What role can a spouse – or partner – have in a kidney transplant offer?

When patients are assessed for a kidney transplant, we explain that the transplant can be from either a living or a deceased donor. Many patients will have discussed their situation with family and friends, who may offer to donate a kidney to them. The most likely person to come forward is their partner.

If a woman has had one or more children with her partner, they may be incompatible due to the sensitizing effect of pregnancy. As a consequence, he may not be able to donate directly to her. Pregnancy-induced sensitization is not a factor for cisgender men, who have higher chances of being compatible with their spouse or partner. The development of anti-HLA antibodies following a pregnancy is one of the main causes of sensitization and clearly a factor that contributes to the discrepancy in numbers of organ offers we see between men and women (5,6).

Women living with CKD are faced with complex decisions when it comes to planning a family. Potential sensitization is one additional factor that women who know they are likely to need a transplant in the future might consider (5,6).

Q3 What do you believe can be done to ensure that there is a more equitable approach to kidney transplantation and care?

There are a number of solutions that could be considered. One that has been particularly successful in the UK in the context of living donation has been the development of the Kidney Sharing Schemes. In this situation, a patient who is incompatible with a donor can enroll in a scheme that shares kidneys around the country to enable compatible transplants to be completed. This has been very successful and has gone some way in correcting the imbalance.

In relation to disparities between sexes specifically, I believe that healthcare systems need to recognize and minimize any disparities in access to transplantation, including assessment and listing. This can be promoted by increased awareness and education amongst both patients and healthcare providers. This will allow greater accessibility to both living and deceased transplantation. With an increased awareness, I would also hope that women feel more empowered to speak with their doctor on the challenges they face, to ensure they are receiving the care they need and hopefully accelerate the process to receiving a kidney transplant.

Our commitment

At Hansa Biopharma, we are committed to finding and developing solutions that can help address the unmet medical needs for patients living with rare immunologic diseases, including those highly sensitized patients, and help raise awareness on the current disparities in kidney donation offering.

*Throughout this article the use of appellatives “man” and “woman” refer to cisgender persons

References

1. Newsletter Transplant 2015-2021. Available at: https://freepub.edqm.eu/publications. Last accessed March 2023.

2. Katz-Greenberg G, et al. Semin Nephrol. 2022. 42:219−229.

3. National Kidney Foundation. ChronicKidney Disease (CKD). Available at: https://www.kidney.org/atoz/content/about-chronic-kidney-disease. Last accessed March 2023.

4. Vinson A. Kidney Int Rep. 2022. 7:1145-1148.

5. Kidney Research Unit. Engaging and supporting women with Chronic Kidney Disease with pre-conception decision-making (including their experiences of COVID 19): A mixed-methods study (CKD-ENGAGE). Available at: http://www.kidneyresearchunit.wales/impact-case-studies.htm?id=34. Last accessed March 2023

6. Bromberger B, et al. J Am Soc Nephrol. 2022. 28: 3025–3033.