Women's Access to Kidney Transplantation

Kidney transplantation is the ideal treatment for people with kidney failure because it offers longer survival, better quality of life, reduced hospitalization, and lower cost relative to dialysis.¹ However, a relative donor shortage means not all kidney failure patients will receive a lifesaving transplant, and it is in this setting that sex and gender disparities in access remain prevalent. Women have a higher prevalence of chronic kidney disease (CKD); however, they are less likely to receive appropriate care and initiate dialysis than men.^2,3 Women are less likely to be referred, evaluated, or waitlisted for a kidney transplant, and less likely to receive a live donor kidney transplant despite being more likely to be a donor.^2,3 Reasons for this disparity are unclear, but likely include a combination of conscious and unconscious provider bias, differential comorbidity burden or frailty distribution, possible differences in candidate self-selection, caregiving burden, as well as biological factors such as pregnancy-induced sensitization.^2,3 This article reviews key evidence documenting sex and gender disparities at multiple steps of the transplant care continuum, from CKD care through to transplant.

Sex Versus Gender Terminology

In general, “sex” refers to biological attributes such as genetic, anatomic, and endocrine traits, whereas “gender” includes social and cultural norms, roles, behaviors, and interactions among women and men.⁴ Although sometimes used interchangeably, sex and gender should be regarded as 2 conceptually distinct entities, and each may affect patients’ choices and outcomes. In recent decades, there has been increasing realization that sex and gender are important determinants of kidney disease progression, referral to transplantation, as well as patients’ outcomes.⁴ In this editorial review, “sex” will be used when discussing biological traits, whereas “gender” will be used when considering factors that likely impact transplant access including gender identity, expression, roles, expectations, and experiences of sexism. Where sex and gender can not be delineated, the phrase ‘sex and gender’ will be used throughout.

Sex and Gender Inequities in CKD and Kidney Failure

In the United States (US) general population, the prevalence of CKD stages 3 to 4 in women is 7.8% compared with 5.9% among men. Among adults with CKD, ∼60% are women⁵; however, 60% of people starting dialysis for kidney failure are men.⁶ The finding that men are more likely to start dialysis for kidney failure despite lower prevalence of CKD is consistent across countries and time.^6,7 There is a physiological explanation for this in that with increasing age estimated glomerular filtration rate declines more quickly in men (vs. women). Possible mechanisms for more rapid estimated glomerular filtration rate decline in men include the role of sex hormones on kidney function and structure, and healthier lifestyles of women, though the clinical evidence to support these theories is considered weak.^2,3 Another possible explanation is the higher all-cause mortality in women with CKD, a competing risk for initiating dialysis.^2,3 This is unlikely to be the entire explanation because once the decision to initiate dialysis has been made, women still seem to fair worse. For example, women are less prepared to initiate dialysis, which brings increased risks for infection,⁸ hospitalization,⁹ and mortality⁹; and they start dialysis later with lower estimated glomerular filtration rate and greater disease severity, than men.⁸ This may, in part, be due to poorer “upstream” CKD care in women. For example, in Sweden women with probable CKD were less likely to receive a formal CKD diagnosis, less likely to be referred to a nephrologist, and less likely to be prescribed guideline-recommended therapies, as compared with men.S1

Sex and Gender Inequities in Referral and Evaluation

Access to kidney transplant involves a series of sequential steps that includes medical referral for transplant evaluation, initiation and completion of the medical evaluation, approval for transplant, followed by placement on the national deceased donor waiting list, and finally, receipt of a living or deceased donor transplant (Figure 1). What we know of sex and gender inequities in access to transplant today is largely limited to the “downstream” steps of waitlisting and transplant, which are collected in some national registries.^6,7,S2 Less is known about the critical and necessary steps of referral and evaluation because this is not routinely captured in surveillance data. Using the Early Steps to Transplant Access Registry,S3,S4 a novel registry of referral and evaluation data from 3 states in southeastern US, women (vs. men) with kidney failure were shown to be 10% less likely to be referred for transplant among those initiating dialysis, 7% less likely to start the evaluation among those that were referred, yet similarly likely to be waitlisted and transplanted as compared with men if they completed the necessary steps of both referral and evaluation.S5 This finding hints that upstream care processes (i.e., those prior to waitlisting) may be more important targets for interventions to reduce sex and gender-based inequities in transplant access. It has also been shown that women with diabetes or hypertension-attributed kidney failure,S6 older age, and higher obesity levels have reduced access compared with men of similar characteristics.S5–S7 The reasons for these disparities remain elusive but hypotheses include lower probability of providers discussing transplant as a treatment option with women, women’s attitudes toward transplant, higher psychosocial and health-related concerns, higher care burden, and lower self-advocacy among women, as well as a lack of awareness of sex and gender disparities among providers.S8–S10 Intersectionality with race and socioeconomic status, which are factors also associated with reduced access to transplant, likely also plays a role though this remains relatively understudied. In a recent review, Gompers et al.S11 identified only 14 US-based studies (with just 2 published from 2015 onward) since the 1990s that examined the intersection of sex and gender with race. Overall, this review highlighted that women of racial or ethnic minorities tend to have the least access to each step of the complex transplant care continuum, and that further research should prioritize examining how racism and sexism interact to shape kidney transplant access.S11

Figure 1.

A multi-level framework for addressing sex and gender inequities in access to kidney transplant across the care continuum. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease.

Sex and Gender Inequities in Waitlisting and Deceased Donor Transplantation

Sex and gender-based disparities in access to the waitlist and subsequent transplant were first reported in the late 1980s.S12 Since then, several studies have shown that women with kidney failure experience a 10% to 20% lower likelihood of being waitlisted as compared with men, and this cannot be explained by differences in demographic or clinical characteristics.^2,3,S13 Though some may consider this a small relative difference, this differential equates to approximately 9000 additional women with kidney failure in the US alone not getting waitlisted for lifesaving transplant every year.⁶ Most studies dedicated to assessing sex and gender disparities in transplant access have historically been conducted in the US, where access to universal healthcare does not exist—though individuals with kidney failure have been eligible for Medicare coverage since 1972—leading many to suggest that access to care via insurance may be the driver of such inequities. However, sex and gender disparities have also been shown in countries with universal healthcare coverage, including Australia,S14 Scotland,S15 France,S16 Germany,S13 and CanadaS17; thus, access to care is unlikely to explain all of the sex and gender-based inequities we observe. It is important to note that sex and gender disparities do occur among children as well, and it has been shown that girls have poorer access to preemptive transplantation when compared with boys.S18

Some studies have shown that, once waitlisted, rates of transplant are comparable between men and women,^6,S13,S19 though women are more likely to be inactive on the waitlist list leading to a potential underestimate of the true sex and gender difference in transplant rates.S20 Potential reasons for women’s reduced access to downstream steps of waitlisting and transplant are likely to be similar to those described above for early transplant steps of referral and evaluation, and may also include sex-specific reasons such as the presence of panel reactive antibodies and active autoimmune diseases, which are more prevalent in women.⁴ It is also likely that physicians view women’s health differently. Accumulating data suggest that physician’s view women as more frail than men and thus are less likely to refer women for transplant, or to deem them medically eligible.S21 It has also been shown that obese women,S14 or women with diabetes,S22 are less likely to be waitlisted or transplanted compared to men with the same level of comorbidities.

Sex and Gender Inequities in Living Donor Transplant

Women are further disadvantaged because they constitute 60% of living kidney donors; however, less than 40% of living donor transplant recipients, a consistent finding across several countries.^2,3,S23 Although there is no conclusive evidence why women donate more than they receive, this inequality likely stems from complex interactions between environmental, biological, and social factors. For example, a study of 10 female donors who donated a kidney to a relative showed that a woman’s decision to donate a kidney is driven by their desire to improve the life and health of recipients, likely stemming from the traditional caregiving roles that women have typically occupied in society.S24 In terms of receipt of living donor transplant, pregnancy-induced sensitization (whereby histocompatibility, required for a donor “match,” is reduced due to antihuman leukocyte antigen-antibodies developed during pregnancy and sustained thereafter) is often considered a barrier for women. Importantly, a 2017 study of more than 2500 patients, showed that participation in a kidney paired exchange program eliminated sex-based differences in living donor kidney transplant, highlighting that despite any biological differences, sex and gender equity in access to living donor transplant can be achieved with the right policies in place.S25

Future Directions

Sex and gender disparities have been identified at all phases of the complex kidney transplant care continuum, in countries where data is available (largely the US, Europe, Canada, and Australia). These inequities are likely to be multifactorial, occur at multiple levels (i.e., individual and neighborhood levels), and accumulate across one’s life. For example, women with kidney failure may be less likely to be referred to a nephrologist, and to live in neighborhoods with reduced opportunities to access specialist care. Cultural and gendered norms may also influence and shape the way women think about seeking care, including donation, and self-health advocacy, and these may be modified by country or region. Women may be further constrained in seeking appropriate care due to caregiving responsibilities traditionally taken on by women. Unfortunately, a comprehensive overview of the barriers for women across this spectrum of care is currently lacking because of the absence of surveillance data with continuous follow-up through each care step. In particular, there is a lack of data outside of the US and Europe, limiting our understanding of sex and gender disparities in transplant access globally. Future research should prioritize the consideration of the multilevel factors that may influence women’s access to transplant across the life course (see Figure 1 as an example), including distinguishing between sex and gender-based factors, and their intersection. Further qualitative research will be essential to gather information on perceptions, attitudes, and experiences regarding sex and gender inequities, including how experiences of racism and sexism and their intersection may shape transplant access. This will allow us to identify specific barriers to transplant access and develop tailored approaches to address sex and gender inequities in transplant and ensure that women with kidney failure have equal access to this life saving resource.

Disclosure

The author declared no competing interests.

Supplementary Material

Supplemental References.