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

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.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.,Bioethics and Organ Transplantation in a Muslim Society.Distribution of the global burden of ckd and common risk factorsThe 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. 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 1Figure 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. 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. 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). 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. 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. 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. 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 HEALTHGender-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., 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.,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.,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). 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

Compiled from the United Nations (2019),United Nations
Report of the Secretary-General on SDG Progress 2019. World Health Organization (2021), United Nations (2020), United Nations Women, (2021), UNESCO (2017), 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. Many of these deaths could be prevented through improved education, prepregnancy health, access to family planning, and high-quality antenatal and perinatal care. Despite a decrease in maternal mortality ratio since 2000, likely reflecting the global focus driven by the Millennium Development GoalsUnited Nations
The Millennium Development Goals Report. and the subsequent Sustainable Development Goals, the incidence of pregnancy-associated complications such as pre-eclampsia, which may impact a woman's long-term kidney health, have not improved.,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.,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 DIFFERENCES IN KIDNEY HEALTH AND ACCESS TO CARE: FOCUS ON SUB-SAHARAN AFRICAIn 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.Gender bias in access to healthcare in Nigeria: a study of end-stage renal disease.,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.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).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 2Figure 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 alOlowu 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.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.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 .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.

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