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Sex and gender differences in chronic kidney disease and access to care around the globe

      Summary

      The difference between sex, the biological construct, and gender, the social construct, may be most evident in settings of vulnerability. Globally, chronic kidney disease is more prevalent among women, but the prevalence of end-stage kidney failure, and especially receipt of kidney replacement therapy, is higher in men. These differences likely reflect a combination of physiological and social/structural risk factors that independently modulate kidney disease and/or its progression. The distribution of the most common risk factors such as hypertension and obesity differ between men and women and may impact disease risk differentially. Social and structural gender-related inequities remain stark across the globe. More women live in poverty, receive less education, and are more dependent on others for health care decision making, but men may have a higher risk of injury, occupational exposures, and less access to screening, prevention, and primary care. In this article, we explore how social determinants of health affect kidney disease risk and access to care differentially across genders, and differently across the globe. We also describe specific challenges experienced by boys and girls with kidney disease, how culture and geography may impact kidney care in places where resources are particularly limited such as sub-Saharan Africa, and give examples of social and structural circumstances that place young men and women at high risk of kidney disease in Mexico and Central America, illustrated by case vignettes. The coronavirus disease-2019 pandemic has raised awareness of pervasive gender-based inequities within all societies. This applies to kidney disease and is not new. The nephrology community must add its voice to the calls for action, for a more just society overall, and for the recognition of the roles of sex and gender as modulators of kidney disease risk and access to care.

      Keywords

      The difference between sex, the biological construct, and gender, the social construct, may be most evident in settings of vulnerability. A recent review has expertly highlighted how health care disparities exist on a biological basis, with men and women having differing biological susceptibility to a disease eg, ischemic heart disease, in which men have a greater risk of obstructive disease in the major coronary arteries whereas women have more microvascular disease.
      • Mauvais-Jarvis F
      • Bairey Merz N
      • Barnes PJ
      • et al.
      Sex and gender: modifiers of health, disease, and medicine.
      Heart disease is the leading cause of death in both sexes, but, overall, diagnoses tend to be more delayed in women and they receive less evidence-based management for acute myocardial infarctions, highlighting the impact of gender on care and outcomes.
      • Mauvais-Jarvis F
      • Bairey Merz N
      • Barnes PJ
      • et al.
      Sex and gender: modifiers of health, disease, and medicine.
      Far less is known about the sex and gender implications for kidney disease. Beyond some diseases (eg, those associated with pregnancy or urinary obstruction having clear sex-based associations), the true reasons why the prevalence of chronic kidney disease (CKD) is generally higher among women, but that of end-stage kidney failure (ESKF) is higher among men, are not well understood. Globally, more men than women receive kidney replacement therapy (KRT), potentially related to underlying biology and faster progression of CKD in men, but likely also in part because women have reduced access to expensive care, especially when costs are out-of-pocket, or women being more likely to choose conservative kidney care rather than dialysis.
      • Ulasi I.
      Gender bias in access to healthcare in Nigeria: a study of end-stage renal disease.
      • Shaikh M
      • Woodward M
      • John O
      • et al.
      Utilization, costs, and outcomes for patients receiving publicly funded hemodialysis in India.
      • Carrero JJ
      • Hecking M
      • Ulasi I
      • Sola L
      • Thomas B.
      Chronic kidney disease, gender, and access to care: a global perspective.
      Dialysis treatment guidelines are not adapted for sex, despite differing body habitus and normal values between men and women. Interestingly, despite potentially receiving a larger dialysis dose given their lower body weights, women on dialysis have disproportionately worse outcomes, including more cardiovascular deaths compared with men.
      • Chronic Kidney Disease Collaboration GBD
      Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
      ,
      • Morton RL
      • Schlackow I
      • Mihaylova B
      • Staplin ND
      • Gray A
      • Cass A.
      The impact of social disadvantage in moderate-to-severe chronic kidney disease: an equity-focused systematic review.
      The relative contributions of sex and gender are not known. In addition, women are generally more likely to be kidney donors, potentially related to greater altruism, perception of fewer bread-winner responsibilities, or in some settings related to pressure imposed by patriarchal families, all likely based on gender rather than sex.
      • Hogan J
      • Couchoud C
      • Bonthuis M
      • Groothoff JW
      • Jager KJ
      • Schaefer F
      • et al.
      Gender disparities in access to pediatric renal transplantation in Europe: data from the ESPN/ERA-EDTA registry.
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      Bioethics and Organ Transplantation in a Muslim Society.

      Distribution of the global burden of ckd and common risk factors

      The age-standardized prevalence, disability-adjusted life-years (DALYs), and deaths per 100,000 population for CKD stratified by world region as classified by the World Bank and sex are depicted in Figure 1a.

      Institute for Health Metrics and Evaluation. GBD compare/viz hub Washington, USA: University of Washington; 2021. Accessed July 16 2021. https://vizhub.healthdata.org/gbd-compare

      In Figure 1a it is interesting to note that despite the actual rates varying across the world, the curves for males and females remain relatively parallel in most regions. Globally, the prevalence of CKD appears highest in women from the Middle East and North Africa, and DALYs and death rates appear highest for men in Latin America and the Caribbean. Strikingly, the Middle east and North Africa stand out because DALYs and death rates are higher in women than in men in this region in contrast to all other regions. Concerningly, incidence rates of CKD also are increasing the most in this region (Figure 1b). To our knowledge, little has been written about this phenomenon, which requires further study. It also is interesting that the prevalence of CKD appears similar in men and women in South Asia, although DALY and death rates remain higher for men. Much more local granular data would be required to dissect, compare, and understand these regional and sex- and/or gender-based differences.
      Figure 1
      Figure 1(A) Global prevalence, disability-adjusted life-years (DALYs), and deaths associated with chronic kidney disease (CKD) by World Bank region (rates per 100K population). Purple curves represent men, and green curves represent women. The axis for each region is different, illustrating differing rates of CKD worldwide over time until 2019. In most regions, the prevalence of CKD is higher in women, whereas the DALYs and death rates are higher in men. The Middle East and North African regions are exceptions to this pattern. Data from each region were obtained from http://ghdx.healthdata.org/gbd-results-tool. Similar data were not available for acute kidney injury. (B) Incidence rates for CKD in men and women across the seven World Bank regions. The incidence of CKD appears to be increasing most rapidly among women and men in the Middle East and North African regions. Abbreviations: SSA, sub-Aaharan Africa_; WB, World Bank_____.
      Before the coronavirus disease-2019 (COVID-19) pandemic, health was improving globally, with life expectancies for men and women reaching 70.9 and 75.9 years, respectively, having improved from 66.8 and 77.3 years in 2000.

      World Health Organization. World health statistics 2021: monitoring health for the SDGs, sustainable development goals Geneva: World Health Organization; 2021. Accessed November 10, 2021. https://apps.who.int/iris/bitstream/handle/10665/342703/9789240027053-eng.pdf

      Despite this improvement, some risk factors for kidney disease continued to increase. Obesity rates in 2016 reached 11.1% in men and 15.1% in women, representing increases of 66% and 70%, respectively, since 2000.

      World Health Organization. World health statistics 2021: monitoring health for the SDGs, sustainable development goals Geneva: World Health Organization; 2021. Accessed November 10, 2021. https://apps.who.int/iris/bitstream/handle/10665/342703/9789240027053-eng.pdf

      Of concern, the sex difference in obesity is highest in low-income counties (LICs), where obesity was almost three times more prevalent among women than among men, although rates were similar in high-income counties (HICs).

      World Health Organization. World health statistics 2021: monitoring health for the SDGs, sustainable development goals Geneva: World Health Organization; 2021. Accessed November 10, 2021. https://apps.who.int/iris/bitstream/handle/10665/342703/9789240027053-eng.pdf

      The age-standardized global prevalence of hypertension in 2015 was 20.1% for women compared with 24.1% for men. Women, however, are diagnosed and treated for hypertension more frequently compared with men.

      World Health Organization. World health statistics 2021: monitoring health for the SDGs, sustainable development goals Geneva: World Health Organization; 2021. Accessed November 10, 2021. https://apps.who.int/iris/bitstream/handle/10665/342703/9789240027053-eng.pdf

      Sex differences in rates of hypertension, however, also vary across countries with male-to-female ratios of 1.54 in HICs, 1.26 in upper-middle-income countries, 1.07 in lower-middle-income countries, and 0.98 in LICs, where hypertension was more prevalent among women than men.

      World Health Organization. World health statistics 2021: monitoring health for the SDGs, sustainable development goals Geneva: World Health Organization; 2021. Accessed November 10, 2021. https://apps.who.int/iris/bitstream/handle/10665/342703/9789240027053-eng.pdf

      The prevalence of tobacco use has decreased in both men and women, but remained higher among men (38.6%) compared with women (8.5%) in 2018.

      World Health Organization. World health statistics 2021: monitoring health for the SDGs, sustainable development goals Geneva: World Health Organization; 2021. Accessed November 10, 2021. https://apps.who.int/iris/bitstream/handle/10665/342703/9789240027053-eng.pdf

      The sex difference, however, has increased, because rates of tobacco use are decreasing faster among women. The prevalence of diabetes globally was estimated to be 9.0% in women and 9.6% in men between ages 20 and 79 years in 2019.
      International Diabetes Federation
      IDF Diabetes Atlas Brussels.
      Globally, the prevalence was highest in the Middle East and North African region (12.2%) and lowest in the African region (4.7%), although the African region had the highest proportion of undiagnosed diabetes (59.7%), compared with the lowest in North America and the Caribbean (37.8%). The global distribution of the most common risk factors for kidney disease therefore is variable and may impact disease risk differentially in women and men.

      GLOBAL GENDER INEQUITIES IMPACTING KIDNEY HEALTH

      Gender-related inequities remain stark across the globe, as highlighted in Table 1, many of which may directly or indirectly impact the risk or outcomes of kidney disease. Many of these disparities have been exacerbated further by the COVID-19 pandemic and prior gains have been lost.

      United Nations Women. Progress on the Sustainable Development Goals: The gender snapshot 2021 New York: United Nations Entity for Gender Equality and the Empowerment of Women (UN Women) Department of Economic and Social Affairs (DESA); 2021. Accessed November 10, 2021.https://www.unwomen.org/en/digital-library/publications/2021/09/progress-on-the-sustainable-development-goals-the-gender-snapshot-2021

      ,

      United Nations. Sustainable develeopment goals New York: United Nations; 2020. Accessed November 10, 2021. https://www.un.org/sustainabledevelopment

      Progress toward gender equality is important to improve the health of women and children, but also is necessary to promote economic growth and social change.

      United Nations. Sustainable develeopment goals New York: United Nations; 2020. Accessed November 10, 2021. https://www.un.org/sustainabledevelopment

      ,
      • Doku DT
      • Bhutta ZA
      • Neupane S.
      Associations of women's empowerment with neonatal, infant and under-5 mortality in low- and /middle-income countries: meta-analysis of individual participant data from 59 countries.
      Gains in access to primary school education and rates of child marriage and female genital mutilation had been made before the pandemic, but many of these have been lost over the past year.

      United Nations. Sustainable develeopment goals New York: United Nations; 2020. Accessed November 10, 2021. https://www.un.org/sustainabledevelopment

      ,
      • Langer A
      • Meleis A
      • Knaul FM
      • et al.
      Women and health: the key for sustainable development.
      More women and girls live in extreme poverty, live with food insecurity, experience more domestic violence, have limited access to secondary education, are engaged in unpaid or underpaid work, and more often are victims of trafficking compared with men (Table 1).

      UN Women. Progress on the sustainable development goals: the gender snapshot 2019 New York: United Nations; 2019. Accessed November 10, 2021.https://www.unwomen.org/en/digital-library/publications/2019/09/progress-on-the-sustainable-development-goals-the-gender-snapshot-2019

      Other gender inequities also have been highlighted during the pandemic, fewer leadership positions are held by women, women are under-represented in research, and despite being the predominant contributors to the health care workforce, their contributions remain underacknowledged.
      • Langer A
      • Meleis A
      • Knaul FM
      • et al.
      Women and health: the key for sustainable development.
      ,
      • Bruce R
      • Cavgias A
      • Meloni L
      • Remigio M.
      Under pressure: women's leadership during the COVID-19 crisis.
      Table 1Global gender-based disparities across the 17 Sustainable Development Goals
      Sustainable Development GoalKnown gaps for women and menGender snapshot 2021 - changes resulting from of COVID-19
      1. No Poverty: End poverty in all its forms everywhere (Extreme poverty defined as living on < US$1.90 a day)
      • 122 women: 100 men aged 25 to 34 live in extreme poverty
      • 45% of women giving birth received maternity cash benefits
      • 41% of employed women and 38% of employed men in low income countries live in extreme poverty (2019)
      • In sub-Saharan Africa the risk of poverty declined from 46% to 28% among those with 6 years of education
      • Women have less control over spending their earnings
      • 435 million women and girls live in extreme poverty (9.2% increase since 2019)
      2. Zero Hunger: end hunger, achieve food security and improved nutrition and promote sustainable agriculture
      • Women small-scale farmers earn on average 30% less than men
      • Gender gap in food insecurity increased to 10% in 2020 from 6% in 2019, higher among women
      3. Good health and well-being: Ensure healthy lives and promote well-being for all at all ages
      • Maternal mortality ratio varies 14 fold across the globe
      • Men tend to take more risks – voiding condoms, using harmful substances, less health care seeking
      • Life expectancy of indigenous women (e.g. Dalit in India) is 1.46 years lower than higher caste women
      • During the pandemic 12 million women in LMIC had gaps in family planning -> 1.4 million unintended pregnancies
      • 113 400 more maternal deaths
      • More women delayed cancer screening (HIC)
      4. Quality education: Ensure inclusive and equitable quality education and promote lifelong learning opportunities for all
      • 750 million adults were illiterate (2016) – 2/3 are women
      • Children of mothers who complete at least primary schooling are more likely to survive
      • Each year of school for a girl reduces the national fertility rate bay 5-10%
      • 1 additional year of education for children led to a 10% increase in income
      • 6 out of 10 youth not in education were women at the end of 2020
      5. Gender equality: Achieve gender equality and empower all women and girls

      • Women are 13% of global landholders
      • If women farmers received same resources as men -> world hunger could decrease by up to 150 million
      • Gender-based inequalities and violence put adolescent girls and young women at risk of HIV.
      • In central Asia 27% more girls do not attend school compared with boys
      • 18 % of women (aged 14-49) experience domestic violence
      • 49 countries have no legislation protecting women from domestic violence
      • 18 countries – men can legally prevent wives from working
      • 39 countries – daughters inherit less than sons
      • 27% of managerial positions globally were occupied by women (2018) who comprise 39% of the workforce
      • Global gender pay gap: 23%
      • 740 million women and girls married before age 18
      • 57% of women 15-49 years are in control of their own sexual relations and use of family planning
      • Women and girls collect water in 80% of households
      • Women make up 76% of medical doctors and nurses (40% doctors, 90% nurses)
      • 234 million fewer women have internet access on mobile phones compared to men
      • Domestic violence increased 40 – 79%
      • Women spend more time on unpaid childcare during the pandemic
      6. Clean water and sanitation: Ensure availability and sustainability of water and sanitation for all
      • Women and girls experience more hardship without access to safe drinking water, sanitation and menstrual hygiene facilities
      • Women predominantly collect water -> more exposure to water-borne diseases e.g. Malaria
      • Fewer women participate in integrated water resource management
      7. Affordable and clean energy: Ensure access to affordable, reliable, sustainable and modern energy for all
      • Energy poverty impacts world hunger by impacting food production
      • Women do most of indoor cooking
      • 32% of renewable energy workforce are women, predominantly in lower paid positions
      8. Decent work and economic growth: Promote sustained, inclusive and sustainable economic growth, full and productive employment and decent work for all
      • 21% global youth (30% women, 13% men) not engaged in work, education or training (2018)
      • Higher health risks for men in extractive work, construction industry, road transport
      • Men have participate less in health campaigns, vaccination programmes etc. because of work migration
      • Women working in flower farming have higher exposure to pesticides/chemicals
      • Women spend 2.6 times more on unpaid domestic work than men
      • Job losses are steeper among women than men during the pandemic -> 54 million women became unemployed, 45 million left the job market
      • Increased unpaid domestic work (globally)
      9. Industry, innovation and infrastructure: Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation
      • 1/3 of researchers are women
      • Women's health research underfunded
      10. Reduced inequalities: Reduce inequality within and among countries
      • Maternal mortality 3 x higher in rural areas
      • Women 15-49 years experiencing domestic violence (2005-2017): 23% Central and S. Asia) vs. 6% (Europe)
      • Migrant women do more domestic work, are more vulnerable to infection, have poorer working and living conditions
      11. Sustainable cities and communities: Make cities and human settlements inclusive, safe, resilient and sustainable
      • 6 of 10 deaths from indoor pollution (4.3 Million total) are women and girls
      • Women living in slums less likely to achieve secondary education
      • Women in slums have less access to antenatal care
      12. Responsible consumption and production: Ensure sustainable consumption and production patterns

      13. Climate action: Take urgent action to combat climate change and its impacts

      14. Life below water: Conserve and sustainably use the oceans, seas and marine resources for sustainable development

      15. Life on land: Protect, restore and promote sustainable use of terrestrial ecosystems, sustainably manage forests, combat desertification, and halt and reverse land degradation and halt biodiversity loss
      • 3 billion rely on inefficient cooking systems (wood, charcoal, dung, coal) -> contribute to pollution, disease
      • 20% of land area was degraded between 2000 and 2015 -> disproportionately affects poor rural women
      • 80% of rural dwellers rely on traditional plant-based medicines
      • Voices of young and indigenous women virtually absent in advocacy, activism for planetary health
      • In 1st round of Nationally Determined Contributions to climate goals -> 64/190 referred to gender
      16. Peace, justice and strong institutions: Promote peaceful and inclusive societies for sustainable development, provide access to justice for all and build effective, accountable and inclusive institutions at all levels
      • most trafficking victims are women and girls
      • more med involved in armed conflicts
      • women chair 18% of government committees on foreign affairs, finance, human rights, defence,
      • women chair 70.1% of gender equality committees
      17. Partnership for the goals: Strengthen the means of implementations and revitalize the Global Partnership for Sustainable Development
      • 15% of women in LIC had internet access (2019) -> information, data gaps
      • Need more data from gender perspectives
      Compiled from the United Nations (2019),
      United Nations
      Report of the Secretary-General on SDG Progress 2019.
      World Health Organization (2021),

      World Health Organization. World health statistics 2021: monitoring health for the SDGs, sustainable development goals Geneva: World Health Organization; 2021. Accessed November 10, 2021. https://apps.who.int/iris/bitstream/handle/10665/342703/9789240027053-eng.pdf

      United Nations (2020),

      United Nations. Sustainable develeopment goals New York: United Nations; 2020. Accessed November 10, 2021. https://www.un.org/sustainabledevelopment

      United Nations Women, (2021),

      United Nations Women. Progress on the Sustainable Development Goals: The gender snapshot 2021 New York: United Nations Entity for Gender Equality and the Empowerment of Women (UN Women) Department of Economic and Social Affairs (DESA); 2021. Accessed November 10, 2021.https://www.unwomen.org/en/digital-library/publications/2021/09/progress-on-the-sustainable-development-goals-the-gender-snapshot-2021

      UNESCO (2017),

      UNESCO. Education impacts the SDGs Paris: UNESCO; 2017. Accessed November 10, 2021. https://educateachild.org/sites/default/files/docs/2017//EAC-SDG_Infographic%20Dec%202016.pdf

      and Manandhar (2018).
      • Manandhar M
      • Hawkes S
      • Buse K
      • Nosrati E
      • Magar V.
      Gender, health and the 2030 agenda for sustainable development.
      Abbreviations: COVID-19, coronavirus disease 2019.
      Global barriers in access to appropriate health care for women are complex, relating to lack of economic power, social position, cultural norms, and competing responsibilities such as child or elder care.
      • Langer A
      • Meleis A
      • Knaul FM
      • et al.
      Women and health: the key for sustainable development.
      ,
      • Murphy A
      • Palafox B
      • Walli-Attaei M
      • et al.
      The household economic burden of non-communicable diseases in 18 countries.
      However, physical access to health centers is not the only barrier. Once a woman reaches a health center, even in a HIC, gender biases impact their care, often negatively, and, interestingly, more often in some cases if the physician is male.
      • Mauvais-Jarvis F
      • Bairey Merz N
      • Barnes PJ
      • et al.
      Sex and gender: modifiers of health, disease, and medicine.
      The maternal mortality ratio (maternal deaths per 100,000 live births) is the most inequitably distributed health indicator, ranging from 1 in 202 live births in LICs to 1 in 5,900 in HICs.

      World Health Organisation. World Health Statistics 2019: monitoring health for the SDGs Geneva: World Health Organization; 2019. Accessed April 13, 2020. https://www.who.int/gho/publications/world_health_statistics/2019/en

      Many of these deaths could be prevented through improved education, prepregnancy health, access to family planning, and high-quality antenatal and perinatal care.

      World Health Organisation. World Health Statistics 2019: monitoring health for the SDGs Geneva: World Health Organization; 2019. Accessed April 13, 2020. https://www.who.int/gho/publications/world_health_statistics/2019/en

      Despite a decrease in maternal mortality ratio since 2000, likely reflecting the global focus driven by the Millennium Development Goals
      United Nations
      The Millennium Development Goals Report.
      and the subsequent Sustainable Development Goals,

      United Nations. Sustainable develeopment goals New York: United Nations; 2020. Accessed November 10, 2021. https://www.un.org/sustainabledevelopment

      the incidence of pregnancy-associated complications such as pre-eclampsia, which may impact a woman's long-term kidney health, have not improved.

      United Nations. Sustainable develeopment goals New York: United Nations; 2020. Accessed November 10, 2021. https://www.un.org/sustainabledevelopment

      ,

      Institute for Health Metrics and Evaluation. Maternal health atlas Seattle, WA: Institute for Health Metrics and Evaluation; 2020. https://maternalhealthatlas.org

      Searching for data on gender and health, one finds that most reports and studies highlight disadvantages for women.
      • Manandhar M
      • Hawkes S
      • Buse K
      • Nosrati E
      • Magar V.
      Gender, health and the 2030 agenda for sustainable development.
      It is important to recognize, however, that some risks and inequities disproportionately affect men, who have a higher risk of injury, homicide, occupational exposures, and poisoning, and less access or use of screening, prevention, and primary care, which also differentially may impact kidney disease risk.

      World Health Organization. World health statistics 2021: monitoring health for the SDGs, sustainable development goals Geneva: World Health Organization; 2021. Accessed November 10, 2021. https://apps.who.int/iris/bitstream/handle/10665/342703/9789240027053-eng.pdf

      ,
      • Manandhar M
      • Hawkes S
      • Buse K
      • Nosrati E
      • Magar V.
      Gender, health and the 2030 agenda for sustainable development.
      In addition, as highlighted earlier, many risk factors for kidney disease also may be more prevalent among men, and CKD progresses faster in men. Attention to inequities impacting both sexes and across genders therefore is required to improve global kidney health.
      • Luyckx VA
      • Al-Aly Z
      • Bello AK
      • et al.
      Sustainable development goals relevant to kidney health: an update on progress.
      In what follows we illustrate some regional differences and disparities affecting kidney health and care, often based on gender, and use specific examples to illustrate where sex and gender impact kidney disease occurrence and risk, highlighting some of the less-appreciated challenges faced by males.

      SEX AND GENDER IN CHILD KIDNEY HEALTH

      Gender differences and drivers of disparities are relevant to the dynamic physiological phases of childhood. In the event of disease, disparities may impact diagnosis, management, and outcomes. A review on gender disparities in children with various systemic diseases other than kidney disease highlights the existing gaps in child-specific, gender-based medicine.
      • Piccini P
      • Montagnani C
      • de Martino M.
      Gender disparity in pediatrics: a review of the current literature.
      Broadly, boys are more likely to have special health care needs compared with girls, independent of educational and behavioral issues.
      • Leiter V
      • Rieker PP.
      Mind the gap: gender differences in child special health care needs.
      From a global perspective, under-resourced regions of South Asia, China, and South America experience gender bias in child health care. This revolves around prenatal sex determination, differential care, and differential access to preventive or curative care determined by families. Gender differences favoring boys has been shown in health care–seeking behavior, and in undertaking life-saving procedures.
      • Khera R
      • Jain S
      • Lodha R
      • Ramakrishnan S.
      Gender bias in child care and child health: global patterns.
      Interestingly, in three-child families, health care of girls is not influenced by the presence of other daughters in the family. On the contrary, brothers of a girl sibling seem to be favored with regard to curative care compared with boys with male siblings.
      • Dixit P
      • Cleland J
      • James KS
      Sex differences in child health and healthcare: a reappraisal for India.
      An understanding of these broader gender gaps is necessary to approach disparities associated with kidney disease.

      Kidney Disease

      Boys have a higher prevalence of kidney disease than girls in early childhood in both developed and resource-limited settings owing to a higher burden of congenital urological disorders.
      • Copelovitch L
      • Warady BA
      • Furth SL.
      Insights from the Chronic Kidney Disease in Children (CKiD) study.
      ,
      • Kamath N
      • Iyengar AA.
      Chronic kidney disease (CKD): an observational study of etiology, severity and burden of comorbidities.
      A difference in the maturity rate of bladder control favoring girls is seen in the early years of childhood.
      • Patra PB
      • Patra S.
      Sex differences in the physiology and pharmacology of the lower urinary tract.
      ,
      • Bauer RM
      • Huebner W.
      Gender differences in bladder control: from babies to elderly.
      Similarly, the prevalence of bed wetting is higher and more severe in boys than in girls. However, distinct voiding postures that constantly prevent relaxation of the pelvic floor and hesitancy to use school toilets by girls put them at risk to develop voiding dysfunction.
      • Shreeram S
      • He JP
      • Kalaydjian A
      • Brothers S
      • Merikangas KR.
      Prevalence of enuresis and its association with attention-deficit/hyperactivity disorder among U.S. children: results from a nationally representative study.
      ,
      • Sureshkumar P
      • Jones M
      • Caldwell PH
      • Craig JC.
      Risk factors for nocturnal enuresis in school-age children.
      Boys with underlying obstructive uropathies experience challenges in complying with the long-term daily routine with clean intermittent catheterization (CIC) to avoid bladder and kidney infections (Box 1). Bladder augmentations and creation of hidden stomas (eg, the Mitrofanoff procedure) have been important advances.
      • Basavaraj DR
      • Harrison SC.
      The Mitrofanoff procedure in the management of intractable incontinence: a critical appraisal.
      Both boys and girls needing CIC report lower health-related quality of life with urethral compared with stomal catheterization.
      • Alencar VP
      • Gomes CM
      • Miranda EP
      • et al.
      Impact of the route of clean intermittent catheterization on quality of life in children with lower urinary tract dysfunction.
      However, abnormal urinary stream, necessity of urinary catheterization amidst friends, or in the presence of improper toilet facilities are important challenges faced by boys, which become problematic especially during teenage years.
      • Hellstrom AL
      • Berg M
      • Solsnes E
      • Holmdahl G
      • Sillen U.
      Feeling good in daily life: from the point of view of boys with posterior urethral valves.
      Although long-term CIC in girls after puberty has not been associated with increased complications,
      • Lindehall B
      • Abrahamsson K
      • Jodal U
      • Olsson I
      • Sillen U.
      Complications of clean intermittent catheterization in young females with myelomeningocele: 10 to 19 years of followup.
      it becomes more complex during menstruation.
      Box 1Arun, 19-year-old transplant recipient, Bangalore
      Arun, a student of class VIII, hailed from a small town in the state of Karnataka, India. At age 14, he presented with kidney failure secondary to undiagnosed posterior urethral valves. The family was eager to go ahead with a preemptive transplantation. Urological preparation for the transplant included initiation of CIC per urethra. He was nonadherent with CIC and experienced recurrent urinary tract infections. On probing, he stated that there was no clean bathroom or privacy to perform CIC in school. He hid this issue from his friends for fear of being socially discriminated. Further counseling witnessed compliance with CIC and Arun successfully received a transplant at the age of 15. To maintain good kidney function, he had to perform CIC every 1 to 2 hours in the initial post-transplant period and thereafter every 3 to 4 hours during the day and use a continuous catheter drain at night. Arun took full responsibility for his kidney care, but because of the challenges he had faced with CIC in school he refused to go back to school and quit formal education. At age 18 he was transitioned to the adult kidney service and maintains good graft function, but stays at home with his parents and is not educated to earn a living. Although the ultimate goal of performing a transplant in a child is to provide a near-normal life, one wonders about 19-year-old Arun's quality of life, future prospects, and sustenance of kidney care.
      Children with kidney stones have an age-dependent sex prevalence, with boys younger than 10 years of age being affected more commonly, whereas girls are over-represented among adolescent stone formers. A low height z score has been reported in girl stone formers compared with boys.
      • Schwaderer AL
      • Raina R
      • Khare A
      • Safadi F
      • Moe SM
      • Kusumi K.
      Comparison of risk factors for pediatric kidney stone formation: the effects of sex.
      With regard to autoimmune-related glomerular disease, female preponderance is known and increases with age in childhood systemic lupus erythematosus, although higher disease activity observed in children younger than age 5 years was not related to gender.
      • Tang SP
      • Lim SC
      • Arkachaisri T.
      Childhood-onset systemic lupus erythematosus: Southeast Asian perspectives.
      ,
      • Lim SC
      • Chan EWL
      • Tang SP.
      Clinical features, disease activity and outcomes of Malaysian children with paediatric systemic lupus erythematosus: a cohort from a tertiary centre.
      Cosmetic issues concern girls with systemic lupus erythematosus requiring prolonged steroid or immunosuppressive therapies, including hirsutism, hair loss, and skin pigmentation. Similar to autoimmune diseases, among children with primary glomerular disease, girls experienced more anxiety and fatigue.
      • Canetta PA
      • Troost JP
      • Mahoney S
      • et al.
      Health-related quality of life in glomerular disease.
      Although the prevalence of minimal change nephrotic syndrome is more common in boys, girls with steroid-sensitive nephrotic syndrome have fewer relapses after puberty, but a higher risk for focal segmental glomerulosclerosis at the onset of nephrotic syndrome.
      • Kummer S
      • von Gersdorff G
      • Kemper MJ
      • Oh J.
      The influence of gender and sexual hormones on incidence and outcome of chronic kidney disease.
      ,
      • Franke I
      • Aydin M
      • Llamas Lopez CE
      • et al.
      The incidence of the nephrotic syndrome in childhood in Germany.

      CKD

      A direct effect of sex on the progression of CKD is not evident in children as reported by the CKD in Children study.
      • Furth SL
      • Abraham AG
      • Jerry-Fluker J
      • et al.
      Metabolic abnormalities, cardiovascular disease risk factors, and GFR decline in children with chronic kidney disease.
      However, tracking distinct trajectories of estimated glomerular filtration rate decline, no sex difference in children with nonglomerular disease was observed, but CKD progressed faster among girls with glomerular disease.
      • Bonneric S
      • Karadkhele G
      • Couchoud C
      • Patzer RE
      • Greenbaum LA
      • Hogan J.
      Sex and glomerular filtration rate trajectories in children.
      Similarly, a prospective study of risk factors for overall progression of children with CKD from India found no differences between girls and boys.
      • Kamath N
      • Iyengar A
      • George N
      • Luyckx VA
      Risk factors and rate of progression of CKD in children.
      In contrast, a large multination study from Europe showed faster progression to ESKF in girls.
      • Hogan J
      • Couchoud C
      • Bonthuis M
      • Groothoff JW
      • Jager KJ
      • Schaefer F
      • et al.
      Gender disparities in access to pediatric renal transplantation in Europe: data from the ESPN/ERA-EDTA registry.

      Kidney Failure, Dialysis, and Transplantation

      Similar to the adult general population, females have a survival advantage in the pediatric general population. but among adults with ESKF, mortality rates are comparable between med and women, irrespective of the type of KRT.
      • Saran R
      • Robinson B
      • Abbott KC
      • et al.
      US Renal Data System 2016 annual data report: epidemiology of kidney disease in the United States.
      In striking contrast, among US children, girls with ESKF (US Renal Data System) are at a higher risk of death than boys.
      • Ahearn P
      • Johansen KL
      • McCulloch CE
      • Grimes BA
      • Ku E.
      Sex disparities in risk of mortality among children with ESRD.
      ,
      • Foster BJ.
      Sex disparities in ESRD-related mortality: a call to action.
      In a retrospective cohort of 14,024 children on dialysis aged 2 to 19 years followed up for a mean of 7.1 years, the death rate was 36% higher in girls receiving either dialysis or transplantation.
      • Ahearn P
      • Johansen KL
      • McCulloch CE
      • Grimes BA
      • Ku E.
      Sex disparities in risk of mortality among children with ESRD.
      Furthermore, girls older than age 13 years/adolescents, Black race, and initiation on hemodialysis were associated with a higher risk of death. The gender disparity persisted despite accounting for demographic characteristics, etiology of ESKF, nutritional, and socioeconomic status. Girls have been observed to have a higher risk of death resulting from cardiovascular complications, infections, and malignancy.
      • Ahearn P
      • Johansen KL
      • McCulloch CE
      • Grimes BA
      • Ku E.
      Sex disparities in risk of mortality among children with ESRD.
      Hypoalbuminemia at the time of ESKF onset also contributed to the risk of mortality in girls.
      In a Dutch cohort study, however, no difference was evident in the survival of girls versus boys with ESKF.
      • Groothoff JW
      • Gruppen MP
      • Offringa M
      • et al.
      Mortality and causes of death of end-stage renal disease in children: a Dutch cohort study.
      Similarly, a recent study of 155 children with ESKF from India found no difference in rates of loss to follow up or mortality based on child sex.
      • Pais P
      • Blydt-Hansen TD
      • Michael Raj JA
      • Dello Strologo L
      • Iyengar A
      Low renal transplantation rates in children with end-stage kidney disease: a study of barriers in a low-resource setting.
      With regard to health-related quality of life in children with advanced CKD (75% on dialysis), a prospective study from India showed low scores, but no difference between boys and girls. In addition, a high caregiver burden (95% mothers) was observed (unpublished data). Girls received less nephrology care before KRT, had a lower risk of receiving a kidney transplant even after initiating dialysis, and a lower likelihood of receiving a preemptive transplant.
      • Hogan J
      • Couchoud C
      • Bonthuis M
      • Groothoff JW
      • Jager KJ
      • Schaefer F
      • et al.
      Gender disparities in access to pediatric renal transplantation in Europe: data from the ESPN/ERA-EDTA registry.
      ,
      • Ahearn P
      • Johansen KL
      • McCulloch CE
      • Grimes BA
      • Ku E.
      Sex disparities in risk of mortality among children with ESRD.
      However, access to transplantation has not been shown to be a major contributor to the survival disparities between girls and boys treated for ESKF.

      SEX AND GENDER DIFFERENCES IN KIDNEY HEALTH AND ACCESS TO CARE: FOCUS ON SUB-SAHARAN AFRICA

      In most of Africa's populations, gender is a major determinant of access and type of school attended as well as work.
      • Colclough C
      • Al-Samarrai A
      • Rose P
      • Tembon M.
      Achieving Schooling for All in Africa.
      This is based on African culture, tradition, and religious and social hierarchy, which confers some society roles by sex.
      • Eguavoen ANT
      • Odiagbe SO
      • Obetoh GI.
      The status of women, sex preference, decision-making and fertility control in ekpoma community of Nigeria.
      These differences may influence income, and thereby access to health care in settings such as sub-Saharan Africa, where health insurance or coverage are not present. As such, studies have shown that sex and gender differences contribute to the social, economic, and biologic determinants and consequences of health and illness, most often to the detriment of women.
      • Ulasi I.
      Gender bias in access to healthcare in Nigeria: a study of end-stage renal disease.
      ,
      • Vlassoff C.
      Gender differences in determinants and consequences of health and illness.
      CKD has a high prevalence in Africa, mainly in sub-Saharan Africa, compared with the rest of the world and the northern part of the African continent, and death rates are high relative to much of the rest of the world (Fig. 1).
      • Chronic Kidney Disease Collaboration GBD
      Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
      ,
      • Arogundade FA
      • Omotoso BA
      • Adelakun A
      • et al.
      Burden of end-stage renal disease in sub-Saharan Africa.
      The accuracy of these data is not known, however, because in many places in sub-Saharan Africa the access to diagnosis of kidney disease (awareness among health care workers, availability of diagnostics tests) remains low, and it is possible that the actual numbers are significantly higher.

      International Society of Nephrology. Global Kidney Health Atlas: a report by the International Society of Nephrology on the global burden of end-stage kidney disease and capacity for kidney replacement therapy and conservative care across world countries and regions. 2019.

      The sex ratio patterns of participants in studies on kidney diseases has changed little with time.
      • Carrero JJ
      • Hecking M
      • Ulasi I
      • Sola L
      • Thomas B.
      Chronic kidney disease, gender, and access to care: a global perspective.
      Most of the CKD screening studies in the adult general population have shown that CKD occurs in young adults in their productive age group, and is more prevalent in women compared with men.
      • Peer N
      • George J
      • Lombard C
      • Steyn K
      • Levitt N
      • Kengne AP.
      Prevalence, concordance and associations of chronic kidney disease by five estimators in South Africa.
      ,
      • Kaze FF
      • Maimouna M
      • Beybey AF
      • et al.
      Prevalence and determinants of chronic kidney disease in urban adults' populations of northern Cameroon.
      The female predominance here may be biologically based, but also may be related to their increased access to free screening, which takes place usually in the house or market (Fig. 2). However, hospital-based studies have also shown that CKD affects young adults, with a male predominance, and this predominance increases among those diagnosed at more advanced stages or at ESKF.
      • Ulasi I.
      Gender bias in access to healthcare in Nigeria: a study of end-stage renal disease.
      ,
      • Olowu WA
      • Niang A
      • Osafo C
      • et al.
      Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: a systematic review.
      ,
      • Ashuntantang G
      • Osafo C
      • Olowu WA
      • et al.
      Outcomes in adults and children with end-stage kidney disease requiring dialysis in sub-Saharan Africa: a systematic review.
      The sex ratio inversion with greater disease severity suggests a greater ability of males to seek medical consultation and to meet health care financing requirements.
      • Arogundade FA
      • Omotoso BA
      • Adelakun A
      • et al.
      Burden of end-stage renal disease in sub-Saharan Africa.
      The low representation of women in hospital-based CKD studies could be related to traditional and cultural beliefs, limited access to school, low income, and therefore the inability to pay for health care. Given the inferior socioeconomic condition of women in this society, women tend to visit traditional healers or local pharmacies first, and seek care at the hospital only once the illness worsens. Men, in contrast, are encouraged to seek specialist or hospital care earlier for appropriate management, given their status as more important members of the household and official bread winners. In addition, when males are ill they generally receive care from their wives, as well as being supported by them, at times even filling in for them at work (eg, in agriculture).
      • Vlassoff C.
      Gender differences in determinants and consequences of health and illness.
      ,
      • Liman HM
      • Makusidi AM
      • Sakajiki AM
      • Umar H
      • Maiyaki AS
      • Awosan JK.
      Gender disparity in survival amongst end-stage renal disease patients on haemodialysis.
      Figure 2
      Figure 2Male to female subject distribution of renal patients in sub-Saharan Africa by medical service location/treatment group, data published between 1990 and 2015. The ratio of men to women increases as the cost of kidney care increases. *Screening data were obtained from a systematic review reported by Stanifer et al.
      • Stanifer JW
      • Jing B
      • Tolan S
      • et al.
      The epidemiology of chronic kidney disease in sub-Saharan Africa: a systematic review and meta-analysis.
      This Figure was presented previously at the World Congress of Nephrology, 2015, by Osafo et al based on systematic reviews reported by Olowu et al
      • Olowu WA
      • Niang A
      • Osafo C
      • et al.
      Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: a systematic review.
      and Ashuntantang et al.
      • Ashuntantang G
      • Osafo C
      • Olowu WA
      • et al.
      Outcomes in adults and children with end-stage kidney disease requiring dialysis in sub-Saharan Africa: a systematic review.
      For patients admitted to the hospital with kidney disease, only a few African countries provide all treatment modalities including hemodialysis, peritoneal dialysis, and kidney transplantation.
      • Arogundade FA
      • Omotoso BA
      • Adelakun A
      • et al.
      Burden of end-stage renal disease in sub-Saharan Africa.
      For patients with ESKF, KRT remains unavailable in some African countries or KRT may be limited to hemodialysis.
      • Arogundade FA
      • Omotoso BA
      • Adelakun A
      • et al.
      Burden of end-stage renal disease in sub-Saharan Africa.
      Among ESKF patients receiving dialysis in Africa, females represent only about a third of the population, regardless of incident or prevalent status; therefore, female gender appears to be a real barrier to access to dialysis in this setting. This observation likely reflects their socioeconomic dependence on men or their families for the financing of health care; this sex difference is compounded by the shortage of human resources and equipment as well as the high cost of treatment.
      • Ulasi I.
      Gender bias in access to healthcare in Nigeria: a study of end-stage renal disease.
      ,
      • Ashuntantang G
      • Osafo C
      • Olowu WA
      • et al.
      Outcomes in adults and children with end-stage kidney disease requiring dialysis in sub-Saharan Africa: a systematic review.
      ,
      • Kwalimwa J
      • Mwaura J
      • Muiva M
      • Bor T
      • Chebor A.
      Barriers to access of quality renal replacement therapy in end-stage renal disease patients at the Kenyatta national hospital.
      ,
      • Banaga AS
      • Mohammed EB
      • Siddig RM
      • et al.
      Why did Sudanese end stage renal failure patients refuse renal transplantation?.
      Few African countries have a kidney transplant program, and mainly are reliant on living-related donors. The low prevalence of kidney transplantation reflects the lack of regulatory frameworks for organ donation, financial constraints, low education level, misperceptions, cultural and religious behavior, and nonavailability of donors.
      • Banaga AS
      • Mohammed EB
      • Siddig RM
      • et al.
      Why did Sudanese end stage renal failure patients refuse renal transplantation?.
      • Lagou AD
      • Coulibaly AP
      • Nigue L
      • Weu MT
      • Ackoundou-N'Guessan KC
      • Gnionsahe DA.
      Adherence factors affecting kidney transplant recipient among patients on maintenance haemodialysis in Côte d'Ivoire.
      • Okafor UH.
      Kidney transplant in Nigeria: a single centre experience.
      • Takure AO
      • Jinadu YO
      • Adebayo SA
      • Shittu OB
      • Salako BL
      • Kadiri S.
      The knowledge, awareness, and acceptability of renal transplantation among patients with end-stage renal disease in Ibadan, Nigeria.
      • Kabbali N
      • Mikou S
      • El Bardai G
      • et al.
      Attitude of hemodialysis patients toward renal transplantation: a Moroccan interregional survey.
      Despite the low number of patients receiving a transplant, male predominance was prominent, again likely owing to cultural behavior or socioeconomic status (Fig. 2). In this setting, it was also observed that women who received a transplant tended to have higher mortality rates, although no sex difference was observed for acute rejection or graft survival .
      • Moosa MR.
      Impact of age, gender and race on patient and graft survival following renal transplantation: developing country experience.
      ,
      • Soliman Y
      • Shawky S
      • Khedr A-E
      • Hassan A
      • Behairy MA.
      Incidence of acute renal allograft rejection in Egyptian renal transplant recipients: a single center experience.
      Women tended to predominate as donors.
      • Osafo C
      • Morton B
      • Ready A
      • Jewitt-Harris J
      • Adu D.
      Among factors associated with skeptical attitudes toward kidney transplantation, young age, male sex, and low awareness were identified; this highlights the need for organization of sensitization campaigns including patients and families, health care providers, and the general population.
      • Kabbali N
      • Mikou S
      • El Bardai G
      • et al.
      Attitude of hemodialysis patients toward renal transplantation: a Moroccan interregional survey.
      If sex and gender disparities in kidney health and in access to kidney care are to be improved in Africa, it is imperative to begin with improving gender equity in childhood with access to school education and empowerment of women in general, as well as increasing awareness in the community of kidney disease, risk factors, and the need for early diagnosis and treatment. Ultimately, achievement of true universal health coverage to provide free access to health care for all will go a long way to removing financial barriers, at least for African women to access kidney care.

      SEX AND GENDER DIFFERENCES IN KIDNEY HEALTH AND ACCESS TO CARE: FOCUS IN MEXICO AND CENTRAL AMERICA

      CKD is a true public health emergency in Central America. In 2017, the CKD prevalence in Central America and Mexico was estimated at 11.9% of the population.

      Institute for Health Metrics and Evaluation. Institute for Health Metrics and Evaluation. GBD results tool. 2017. Accessed November 10, 2021. http://ghdx.healthdata.org/gbd-results-tool

      Prevalence was slightly higher in females (12.3%) than in males (11.5%). CKD represented 7.6% of total mortality in 2017, ranking as the second leading cause of death.

      Institute for Health Metrics and Evaluation. Institute for Health Metrics and Evaluation. GBD results tool. 2017. Accessed November 10, 2021. http://ghdx.healthdata.org/gbd-results-tool

      The age-standardized CKD mortality rate was 42.1 per 100,000 population, a 60.9% increase between 1990 and 2017, ranging from 71.4 per 100,000 in El Salvador to 13.0 per 100,000 in Honduras. The age-standardized CKD mortality rate was higher among males.
      • Chronic Kidney Disease Collaboration GBD
      Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
      ,

      Institute for Health Metrics and Evaluation. Institute for Health Metrics and Evaluation. GBD results tool. 2017. Accessed November 10, 2021. http://ghdx.healthdata.org/gbd-results-tool

      The highest estimated rates of age-standardized CKD DALYs were in El Salvador (1,821), Mexico (1,652), Nicaragua (1,571), and Guatemala (1,072), all more than 1,000 DALYs per 100,000. The age-standardized CKD DALY was higher among males (1,379) than in females (1,151).
      In Mexico, age-standardized rates owing to CKD between 1990 and 2017 increased 102%, from 28.7 per 100,000 to 58.1 per 100,000, while DALYs increased 94%.

      Institute for Health Metrics and Evaluation. Institute for Health Metrics and Evaluation. GBD results tool. 2017. Accessed November 10, 2021. http://ghdx.healthdata.org/gbd-results-tool

      In the same period, the CKD mortality rate increased 122.3% for men and 84.4% for women. The CKD standardized mortality rate was 64.9 for men and 52.2 for women. The male mortality rate exceeded the female mortality rate for all causes of CKD in 2017. Until 2010, the mortality rate for all type 1 and type 2 diabetes had been higher for women, but as of 2011 the pattern changed. As reported nationally, in most states the death rate from CKD was higher for men compared with women.
      • Agudelo-Botero M
      • Valdez-Ortiz R
      • Giraldo-Rodríguez L
      • et al.
      Overview of the burden of chronic kidney disease in Mexico: secondary data analysis based on the Global Burden of Disease Study 2017.
      In Jalisco, the mortality rate in males increased 101%, from 33.1 to 66.8 per 100,000, while in females the mortality rate increased 45.2%, from 33.2 to 48.2 per 100,000.

      Institute for Health Metrics and Evaluation. Institute for Health Metrics and Evaluation. GBD results tool. 2017. Accessed November 10, 2021. http://ghdx.healthdata.org/gbd-results-tool

      ,
      • Agudelo-Botero M
      • Valdez-Ortiz R
      • Giraldo-Rodríguez L
      • et al.
      Overview of the burden of chronic kidney disease in Mexico: secondary data analysis based on the Global Burden of Disease Study 2017.
      Most of the increase in CKD mortality in El Salvador, Nicaragua, and Guatemala has been attributed to CKD of unknown etiology (CKDu),
      • Weaver VM
      • Fadrowski JJ
      • Jaar BG.
      Global dimensions of chronic kidney disease of unknown etiology (CKDu): a modern era environmental and/or occupational nephropathy?.
      while in Mexico type 2 diabetes and hypertension represent more than 50% of CKD deaths, except in some hot spot areas, where CKDu is highly prevalent.
      • Agudelo-Botero M
      • Valdez-Ortiz R
      • Giraldo-Rodríguez L
      • et al.
      Overview of the burden of chronic kidney disease in Mexico: secondary data analysis based on the Global Burden of Disease Study 2017.
      ,
      • Aguilar DJ
      • Madero M.
      Other potential CKD hotspots in the world: the cases of Mexico and the United States.
      ,
      • Garcia-Garcia G
      • Gutierrez-Padilla A
      • Perez-Gomez HR
      • et al.
      Chronic kidney disease of unknown cause in Mexico: the case of Poncitlan.
      It has been suggested that the higher mortality in males could be owing to a faster progression to end-stage renal disease, lower adherence to treatment, and lower use of health services.
      • Chronic Kidney Disease Collaboration GBD
      Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
      ,
      • Agudelo-Botero M
      • Valdez-Ortiz R
      • Giraldo-Rodríguez L
      • et al.
      Overview of the burden of chronic kidney disease in Mexico: secondary data analysis based on the Global Burden of Disease Study 2017.
      There also is evidence of substantial gender disparities in access to CKD care in the region. Overall, access to renal replacement therapy has been higher in males than in females. Female prevalence in dialysis ranged between 32% in El Salvador
      • García-Trabanino R
      • Trujillo Z
      • Colorado AV
      • Magaña Mercado S
      • Henríquez CA
      (ANHAES). Prevalence of patients receiving renal replacement therapy in El Salvador in 2014.
      to 42% in Guatemala.
      • Lou-Meda RM
      • Valle AL
      • Urla C
      • Mazariegos J.
      Epidemiologic and socioeconomic profile of Guatemalan hemodialysis patients: assessment and dissemination via a free-access information system.
      In a report of dialysis enrollment in Guatemala, sex distribution was different between the Southwest departments, where CKDu is highly prevalent, and the rest of the country. In the Southwest, 57.8% of enrollees were male compared with 49.3% in the other departments.
      • Laux TS
      • Barnoya J
      • Guerrero DR
      • Rothstein M.
      Dialysis enrollment patterns in Guatemala: evidence of the chronic kidney disease of non-traditional causes epidemic in Mesoamerica.
      In Mexico, females represent 42% of the incident dialysis population,
      • Garcia-Garcia G
      • Monteon-Ramos JF
      • Garcia-Bejarano H
      • et al.
      Renal replacement therapy among disadvantaged populations in Mexico: a report from the Jalisco Dialysis and Transplant Registry (REDTJAL).
      and 38% of patients receiving kidney transplants.
      • Garcia-Garcia G
      • Tonelli M
      • Ibarra-Hernandez M
      • Chavez-Iñiguez JS
      • Oseguera-Vizcaino MC.
      Access to kidney transplantation in Mexico, 2007-2019: a call to end disparities in transplant care.
      The following vignettes are taken from anthropologically anchored, interdisciplinary work on the emergence of unexplained forms of CKD among communities living around Lake Chapala in West-Central Mexico, and illustrate the gender impact on CKD risk and access to care. Those suffering from the condition attend Hospital Civil de Guadalajara, Mexico, a tertiary-care facility for poor and uninsured Mexicans. The lake region compares somewhat differently with endemic countries in Central America in terms of demographics considered vulnerable to new forms of CKD. In Costa Rica, El Salvador, and Nicaragua, what is referred to as CKD of nontraditional origin or Mesoamerican nephropathy, disproportionately affects working-age men.
      • Wesseling C
      • Glaser J
      • Rodríguez-Guzmán J
      • et al.
      Chronic kidney disease of non-traditional origin in Mesoamerica: a disease primarily driven by occupational heat stress.
      Mesoamerican nephropathy, nevertheless, does not result from anything intrinsic to being male, but to the particular nature of work performed primarily by men in the region (ie, high-intensity agricultural work in strong heat, notably sugar cane cutting). Within the Mexican context, a more diverse set of conditions appear to shape the emergence of CKD. Our particular case concerns the municipality of Poncitlán, a cluster of villages and small towns, close to lake Chapala, characterized by impoverishment, highly dependent on a precarious informal economy, which includes subsistence and industrialized agriculture, construction work, fishing, and domestic work. The municipality is embedded in an environment that suffers pollution and contamination and has inadequate access to health care and welfare.
      • Kierans C.
      ,
      • Kierans C
      • Padilla-Altamira C.
      Describing chronic kidney disease of unknown origin; anthropological noticing and the residual category.
      In this setting, it is age rather than gender that takes precedence, with local children younger than 18 being 10 times more likely to experience kidney failure than the state average, and adults 4 times more likely.
      • Garcia-Garcia G
      • Gutierrez-Padilla A
      • Perez-Gomez HR
      • et al.
      Chronic kidney disease of unknown cause in Mexico: the case of Poncitlan.
      The vignettes (Boxes 3,4,5 ) provide some insight into these complex overlapping concerns.
      Box 2Domingo, died from unexplained CKD at age 23, Agua Caliente
      Domingo is from the small lakeside village of Agua Caliente. Like many village children growing up, he played and bathed in the lake, attended the local school, and worked with his family in the cornfields. Domingo's parents were subsistence farmers, who supplemented a meager income by working with local fishermen. After finishing school at 15, he continued in the informal economy, moving between construction work, agricultural labor, and occasional shop work. At the age of 22, with little warning, Domingo fell ill. He was diagnosed with what everyone in the small village now knows to be enfermedad de los riñones (kidney disease) a diagnosis his mother had feared, having seen the disease claim the lives of other young people in their small community. Like her neighbors, she wondered about their consumption of contaminated fish and polluted water and the poor soil they had for farming. Domingo, too, feared the condition. Apprehensive of hospital treatment, he opted to take natural remedies, only to end up on hospital-based peritoneal dialysis, with his kidneys in the end stages of functioning. His family were required to construct a peritoneal dialysis room in their small adobe house, at significant cost. Despite their best efforts, the room was never completed. Domingo died from complications of CKD at the hospital for the uninsured. He was 23.
      Box 3Juan, age 27, transplant recipient, Mezcala
      Juan was diagnosed with an unexplained variant of CKD at the age of 20. He had already lost his uncle, just 2 years older, and his younger brother to the condition. Juan grew up in Mezcala, a small town approximately 7 km from the village of Agua Caliente. Like Domingo, he also worked as a laborer on farms and building sites until he was hired as a gardener by a well-off American expatriate living in the prosperous town of Chapala. When Juan became unwell, his mother, who already lost one son to CKD, took him straight to Hospital Civil, where his kidneys also were nearing the end stages of functioning. Juan was 24 years old. In contrast to Domingo, Juan's employer helped him to secure health insurance from the Mexican Institute of Social Security, the health care system supporting those in formal employment, and the largest health care provider in the country. This substantially reduced out-of-pocket expenses, as well as the efforts his family would have had to make to negotiate and finance health care and medications. As a consequence, his family had less difficulty accommodating a peritoneal dialysis regimen at home. After 2 years on peritoneal dialysis, Juan received a kidney, donated by his father. After recovering from surgery, he returned to his gardening work.
      Box 4Lupita, died from CKD at age 25, Agua Caliente
      A year after giving birth to her second child, at the age of 20, Lupita was diagnosed with CKD. She was a single mother, living with her two children and her parents in their house in Agua Caliente. One day, having returned from Guadalajara, where she worked as a trabajadora doméstica (domestic worker), she felt unwell. Her face and feet were swollen; she was short of breath and lethargic. Her family, uninsured, took her to Hospital Civil, where she was diagnosed. Her doctors could not explain to her why her kidneys were failing and told her that her kidneys were very small; they had not fully developed. After months of struggling financially to secure hemodialysis treatment, Lupita and her family approached a number of philanthropic charities, based in the city, for help. From them, she found support for up to two dialysis sessions per week. This was far from sufficient, and, in addition, they had to visit the charities to make a request each month. Finding it difficult to sustain such efforts, they explored options for an organ transplant. Both parents willingly offered kidneys, but only her father's was suitable. With additional financial support from charities, relatives, and friends, among other benefactors, they completed all required transplant protocols and tests. Sadly, as a result of her deteriorating health and complications, Lupita died just months before surgery. She was 25.
      The vignettes highlight that the wider structural determinants of CKD must be taken seriously. These include both the complex conditions of its emergence and problems in accessing timely and affordable renal care. Interlocutors living around Lake Chapala raise continual concern about their living environment, in particular the widespread contamination of local wells, aquifers, and hot springs; corroding pipes that carry local domestic water supplies; inadequate sewage and sanitation facilities; contaminated fish; poorly irrigated soil for subsistence agriculture; and the widespread use of unregulated agrochemicals. If gender divisions and inequalities are implicated here, they do so as features of social life, not as determinants per se, and are reflected in established divisions or work, family responsibilities, and cultures of care. Regarding the clustering and emergence of CKD within the region, age and social inequality are of critical importance and are compounded further by uneven access to modalities of dialysis and organ transplantation, both heavily reliant on out-of-pocket expenses with catastrophic consequences for uninsured, precarious, and already impoverished Mexicans.
      Access to, and the organization of, renal and transplant services in Mexico is fragmented, characterized by inequality, and administered by an insurance-based social security system that is linked to the labor market system.
      • Kierans C.
      ,
      • Kierans C
      • Padilla-Altamira C
      • Garcia-Garcia G
      • Ibarra-Hernandez M
      • Mercado FJ.
      When health systems are barriers to health care: challenges faced by uninsured Mexican kidney patients.
      ,

      Garcia-Garcia G, Chavez-Iñiguez J, Vazquez-Rangel A, et al. Nephrology in Mexico. In: Moura-Neto J, Divino-Filho J, Ronco C, eds.Nephrology Worlwide. Springer Nature; 2021:157-172.

      Those without formal employment fall outside insurance safety nets and are dependent on the subsidized care of the hospitals of the Health Ministry. Systemic fragmentation and inadequate financing of renal care stand as major structural barriers to health care access. Moreover, they proliferate a range of further barriers and challenges, such as fragmentation, which militates against an integrated system of organ sharing. This means kidneys for transplant are dependent predominantly on living-related donors, which place the burden of effort and cost firmly on already poor families. Renal replacement therapies are heavily reliant on continuous ambulatory peritoneal dialysis. This is performed in patients’ homes, many of which are inappropriate for the quasiclinical requirements it demands, or the high financial and emotional costs it requires. Securing treatment for those without insurance relies on the continual and invisible labor of patients and their families to navigate and make sense of a less-than-visible infrastructure of services, while negotiating access to a variety of expertise (clinical, laboratory testing, psychological evaluation, pharmacies, to name but a few), in addition to sourcing financial help from family, friends, philanthropic associations, businesses, politicians, public bodies, and the general public. These barriers to treatment incur untold costs for those with the least resources and capacities to meet them.
      • Kierans C.
      ,
      • Kierans C
      • Padilla-Altamira C
      • Garcia-Garcia G
      • Ibarra-Hernandez M
      • Mercado FJ.
      When health systems are barriers to health care: challenges faced by uninsured Mexican kidney patients.
      Therefore, although CKD prevalence in this region is slightly higher in females, mortality resulting from CKD is significantly higher in males. This could be the result of both sex- and gender-associated factors, including occupational factors, faster progression to end-stage renal disease, lower compliance with treatment, and lower use of health services. Access to dialysis and transplantation is lower in females than in males. Psychosocial and economic factors, as well as discrimination rooted in sociocultural attitudes toward women, have been suggested as a possible explanation for this finding.
      • Piccoli GB
      • Alrukhaimi M
      • Liu ZH
      • Zakharova E
      • Levin A
      • Committee WKDS.
      What we do and do not know about women and kidney diseases; questions unanswered and answers unquestioned: reflection on World Kidney Day and International Woman's Day.

      CONCLUSIONS

      Given the vast complexity of the impact of sex and gender on the burden of kidney disease globally, it is an almost impossible task to do this topic justice. In highlighting the examples of the impact of gender and sex on kidney health in children, many of which are universal, to specific challenges faced in sub-Sharan Africa and in Central America, where access to kidney care in general is limited, we have attempted to illustrate how sex and gender differentially impact kidney health, and in context-specific ways. Overall, it is women's lives that tend to be more impacted by the many social and structural factors illustrated in Table 1, with each factor impacting her own health as a child, as a mother, her safety, her ability to care for her family, and her ability to seek and access health care when needed.
      • Maule SP
      • Ashworth DC
      • Blakey H
      • Osafo C
      • Moturi M
      • Chappell LC
      • et al.
      CKD and pregnancy outcomes in Africa: a narrative review.
      All of these factors impact the health of a woman's kidneys and those of her children throughout their lives, and mandate urgent calls for improvement in gender equity across all 17 Sustainable Development Goals. The more rapid progression of kidney disease in men, observed almost globally, likely has a more biologic basis, which must not be overlooked, and the intersections with occupational, structural, and climate risk factors must be understood and addressed. The COVID-19 pandemic has raised awareness of pervasive gender-based inequities within all societies, the nephrology community must add its voice to the calls for action, for a more just society overall, and for the recognition of the roles of sex and gender as modulators of kidney disease risk and access to care.

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