Key Points
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The proportion of women with predialysis chronic kidney disease (CKD) is higher than that of men; this difference is likely due to the longer life expectancy of women and possibly to CKD overdiagnosis with use of estimated glomerular filtration rate equations
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Kidney function declines faster in men than women, possibly owing to unhealthier lifestyles in men and the protective effects of oestrogens or the damaging effects of testosterone
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More men than women start renal replacement therapy (RRT) not only owing to faster CKD progression in men but also because elderly women are more likely to choose conservative care
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Mortality is higher among men at all levels of predialysis CKD, whereas mortality among individuals on RRT is similar for men and women
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Women have reduced access to deceased donor transplantation compared with men, likely owing to higher levels of preformed antibodies, whereas access to living donor kidney transplantation in some countries seems equal
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The perceived health-related quality of life of women on RRT is poorer than that of men, and women report a higher symptom burden and greater symptom severity than men
Abstract
Improved understanding of sex and gender-specific differences in the aetiology, mechanisms and epidemiology of chronic kidney disease (CKD) could help nephrologists better address the needs of their patients. Population-based studies indicate that CKD epidemiology differs by sex, affecting more women than men, especially with regard to stage G3 CKD. The effects of longer life expectancy on the natural decline of glomerular filtration rate (GFR) with age, as well as potential overdiagnosis of CKD through the inappropriate use of GFR equations, might be in part responsible for the greater prevalence of CKD in women. Somewhat paradoxically, there seems to be a preponderance of men among patients starting renal replacement therapy (RRT); the protective effects of oestrogens in women and/or the damaging effects of testosterone, together with unhealthier lifestyles, might cause kidney function to decline faster in men than in women. Additionally, elderly women seem to be more inclined to choose conservative care instead of RRT. Dissimilarities between the sexes are also apparent in the outcomes of CKD. In patients with predialysis CKD, mortality is higher in men than women; however, this difference disappears for patients on RRT. Although access to living donor kidneys among men and women seems equal, women have reduced access to deceased donor transplantation. Lastly, health-related quality of life while on RRT is poorer in women than men, and women report a higher burden of symptoms. These findings provide insights into differences in the underlying pathophysiology of disease as well as societal factors that can be addressed to reduce disparities in access to care and outcomes for patients with CKD.
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References
- 1
Mosca, L., Barrett-Connor, E. & Wenger, N. K. Sex/gender differences in cardiovascular disease prevention: what a difference a decade makes. Circulation 124, 2145–2154 (2011).
- 2
Carrero, J. J. Gender differences in chronic kidney disease: underpinnings and therapeutic implications. Kidney Blood Pressure Res. 33, 383–392 (2010).
- 3
Cobo, G. et al. Sex and gender differences in chronic kidney disease: progression to end-stage renal disease and haemodialysis. Clin. Sci. (Lond.) 130, 1147–1163 (2016).
- 4
National Kidney, F. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am. J. Kidney Dis. 39, S1–S266 (2002).
- 5
Nagata, M. et al. Trends in the prevalence of chronic kidney disease and its risk factors in a general Japanese population: the Hisayama Study. Nephrol. Dial. Transplant. 25, 2557–2564 (2010).
- 6
Lu, C. et al. Prevalence and risk factors associated with chronic kidney disease in a Uygur adult population from Urumqi. J. Huazhong Univ. Sci. Technolog Med. Sci. 30, 604–610 (2010).
- 7
Bongard, V. et al. [Assessment and characteristics of chronic renal insufficiency in France]. Ann. Cardiol. Angeiol. (Paris) 61, 239–244 (2012).
- 8
Roth, M., Roderick, P. & Mindell, J. (Kidney disease and renal function. (Health survey for England. Volume 1. Health and lifestyles) (The NHS Information Centre, 2010).
- 9
Murphy, D. et al. Trends in prevalence of chronic kidney disease in the United States. Ann. Intern. Med. 165, 473–481 (2016).
- 10
Otero, A. Gayoso, P., G. F. & de Francisco, A. EPIRCE Study Group. prevalence of chronic renal disease in Spain: results of the EPIRCE study. Nefrologia 30, 78–86 (2010).
- 11
Cirillo, M. et al. Low glomerular filtration in the population: prevalence, associated disorders, and awareness. Kidney Int. 70, 800–806 (2006).
- 12
Zdrojewski, L. et al. Prevalence of chronic kidney disease in a representative sample of the Polish population: results of the NATPOL 2011 survey. Nephrol. Dial. Transplant. 31, 433–439 (2016).
- 13
Ong-Ajyooth, L., Vareesangthip, K., Khonputsa, P. & Aekplakorn, W. Prevalence of chronic kidney disease in Thai adults: a national health survey. BMC Nephrol. 10, 35 (2009).
- 14
Gasparini, A. et al. Prevalence and recognition of chronic kidney disease in Stockholm healthcare. Nephrol. Dial. Transplant. 31, 2086–2094 (2016).
- 15
Sahin, I. et al. Prevalence of chronic kidney disease in the Black Sea Region, Turkey, and investigation of the related factors with chronic kidney disease. Ren. Fail. 31, 920–927 (2009).
- 16
Tanamas, S. K. et al. AusDiab 2012: the Australian diabetes, obesity and lifestyle study (Baker IDI Heart and Diabetes Institute, 2013).
- 17
Vinhas, J. et al. Prevalence of chronic kidney disease and associated risk factors, and risk of end-stage renal disease: data from the PREVADIAB study. Nephron Clin. Pract. 119, c35–c40 (2011).
- 18
Anand, S. et al. Prevalence of chronic kidney disease in two major Indian cities and projections for associated cardiovascular disease. Kidney Int. 88, 178–185 (2015).
- 19
Arora, P. et al. Prevalence estimates of chronic kidney disease in Canada: results of a nationally representative survey. CMAJ 185, E417–E423 (2013).
- 20
Epidemiology & Disease Control Division, Ministry of Health, Singapore. National Health Survey 2010 (MOH Singapore, 2011).
- 21
Suleymanlar, G. et al. A population-based survey of Chronic REnal Disease In Turkey—the CREDIT study. Nephrol. Dial. Transplant. 26, 1862–1871 (2011).
- 22
Shin, H. Y. & Kang, H. T. Recent trends in the prevalence of chronic kidney disease in Korean adults: Korean National Health and Nutrition Examination Survey from 1998 to 2013. J. Nephrol. 29, 799–807 (2016).
- 23
Chen, W. et al. Prevalence and risk factors associated with chronic kidney disease in an adult population from southern China. Nephrol. Dial. Transplant. 24, 1205–1212 (2009).
- 24
Juutilainen, A. et al. Trends in estimated kidney function: the FINRISK surveys. Eur. J. Epidemiol. 27, 305–313 (2012).
- 25
Chen, W. et al. Prevalence and risk factors of chronic kidney disease: a population study in the Tibetan population. Nephrol. Dial. Transplant. 26, 1592–1599 (2011).
- 26
Zhang, L. et al. Prevalence and factors associated with CKD: a population study from Beijing. Am. J. Kidney Dis. 51, 373–384 (2008).
- 27
Zhang, L. et al. Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet 379, 815–822 (2012).
- 28
Glassock, R. J., Warnock, D. G. & Delanaye, P. The global burden of chronic kidney disease: estimates, variability and pitfalls. Nat. Rev. Nephrol. 13, 104–114 (2017).
- 29
Glassock, R., Delanaye, P. & El Nahas, M. An age-calibrated classification of chronic kidney disease. JAMA 314, 559–560 (2015).
- 30
O'Hare, A. M. et al. Age affects outcomes in chronic kidney disease. J. Am. Soc. Nephrol. 18, 2758–2765 (2007).
- 31
Inker, L. A. et al. Effects of race and sex on measured GFR: the multi-ethnic study of atherosclerosis. Am. J. Kidney Dis. 68, 743–751 (2016).
- 32
Neugarten, J., Kasiske, B., Silbiger, S. R. & Nyengaard, J. R. Effects of sex on renal structure. Nephron 90, 139–144 (2002).
- 33
Inker, L. A. et al. Performance of glomerular filtration rate estimating equations in a community-based sample of Blacks and Whites: the multiethnic study of atherosclerosis. Nephrol. Dial. Transplant. https://doi.org/10.1093/ndt/gfx042 (2017).
- 34
Wetzels, J. F., Willems, H. L. & den Heijer, M. Age- and gender-specific reference values of estimated glomerular filtration rate in a Caucasian population: results of the Nijmegen Biomedical Study. Kidney Int. 73, 657–658 (2008).
- 35
Elseviers, M. M., Verpooten, G. A., De Broe, M. E. & De Backer, G. G. Interpretation of creatinine clearance. Lancet 1, 457 (1987).
- 36
Neugarten, J., Acharya, A. & Silbiger, S. R. Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J. Am. Soc. Nephrol. 11, 319–329 (2000).
- 37
Jafar, T. H. et al. The rate of progression of renal disease may not be slower in women compared with men: a patient-level meta-analysis. Nephrol. Dial. Transplant. 18, 2047–2053 (2003).
- 38
Eriksen, B. O. & Ingebretsen, O. C. The progression of chronic kidney disease: a 10-year population-based study of the effects of gender and age. Kidney Int. 69, 375–382 (2006).
- 39
Evans, M. et al. The natural history of chronic renal failure: results from an unselected, population-based, inception cohort in Sweden. Am. J. Kidney Dis. 46, 863–870 (2005).
- 40
Halbesma, N. et al. Gender differences in predictors of the decline of renal function in the general population. Kidney Int. 74, 505–512 (2008).
- 41
Grams, M. E., Chow, E. K., Segev, D. L. & Coresh, J. Lifetime incidence of CKD stages 3–5 in the United States. Am. J. Kidney Dis. 62, 245–252 (2013).
- 42
Turin, T. C. et al. Lifetime risk of ESRD. J. Am. Soc. Nephrol. 23, 1569–1578 (2012).
- 43
van den Brand, J. et al. Lifetime risk of renal replacement therapy in Europe: a population-based study using data from the ERA-EDTA Registry. Nephrol. Dial. Transplant. 32, 348–355 (2017).
- 44
ERA-EDTA Registry. ERA-EDTA Registry annual report 2015 (ERA-EDTA Registry, 2017).
- 45
United States Renal Data System. USRDS annual data report: epidemiology of kidney disease in the United States (USRDS, 2016).
- 46
De Nicola, L. et al. Prevalence and cardiovascular risk profile of chronic kidney disease in Italy: results of the 2008–2012 National Health Examination Survey. Nephrol. Dial. Transplant. 30, 806–814 (2015).
- 47
Sparke, C. et al. Estimating the total incidence of kidney failure in Australia including individuals who are not treated by dialysis or transplantation. Am. J. Kidney Dis. 61, 413–419 (2013).
- 48
Nitsch, D. et al. Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis. BMJ 346, f324 (2013).
- 49
Hemmelgarn, B. R. et al. Rates of treated and untreated kidney failure in older versus younger adults. JAMA 307, 2507–2515 (2012).
- 50
Faruque, L. I. et al. Factors associated with initiation of chronic renal replacement therapy for patients with kidney failure. Clin. J. Am. Soc. Nephrol. 8, 1327–1335 (2013).
- 51
Morton, R. L., Turner, R. M., Howard, K., Snelling, P. & Webster, A. C. Patients who plan for conservative care rather than dialysis: a national observational study in Australia. Am. J. Kidney Dis. 59, 419–427 (2012).
- 52
Chandna, S. M. et al. Rate of decline of kidney function, modality choice, and survival in elderly patients with advanced kidney disease. Nephron 134, 64–72 (2016).
- 53
Coresh, J. et al. Chronic kidney disease awareness, prevalence, and trends among U. S. adults, 1999 to 2000. J. Am. Soc. Nephrol. 16, 180–188 (2005).
- 54
Kausz, A. T. et al. Late initiation of dialysis among women and ethnic minorities in the United States. J. Am. Soc. Nephrol. 11, 2351–2357 (2000).
- 55
Xue, J. L., Eggers, P. W., Agodoa, L. Y., Foley, R. N. & Collins, A. J. Longitudinal study of racial and ethnic differences in developing end-stage renal disease among aged medicare beneficiaries. J. Am. Soc. Nephrol. 18, 1299–1306 (2007).
- 56
Obrador, G. T. et al. Level of renal function at the initiation of dialysis in the U. S. end-stage renal disease population. Kidney Int. 56, 2227–2235 (1999).
- 57
Stel, V. S. et al. Level of renal function in patients starting dialysis: an ERA-EDTA Registry study. Nephrol. Dial. Transplant. 25, 3315–3325 (2010).
- 58
Hecking, M. et al. Sex-specific differences in hemodialysis prevalence and practices and the male-to-female mortality rate: the Dialysis Outcomes and Practice Patterns Study (DOPPS). PLoS Med. 11, e1001750 (2014).
- 59
Stel, V. S. et al. Prevalence of co-morbidity in different European RRT populations and its effect on access to renal transplantation. Nephrol. Dial. Transplant. 20, 2803–2811 (2005).
- 60
Carrero, J. J. et al. Sex differences in the impact of diabetes on mortality in chronic dialysis patients. Nephrol. Dialysis. Transplant. 26, 270–276 (2011).
- 61
Palmer, B. F. & Clegg, D. J. Gonadal dysfunction in chronic kidney disease. Rev. Endocr. Metabol. Disord. 18, 117–130 (2017).
- 62
Yu, J. et al. Association between testosterone and mortality risk among U.S. males receiving dialysis. Am. J. Nephrol. 46, 195–203 (2017).
- 63
Carrero, J. J. & Stenvinkel, P. The vulnerable man: impact of testosterone deficiency on the uraemic phenotype. Nephrol. Dial. Transplant. 27, 4030–4041 (2012).
- 64
Carrero, J. J. et al. Low serum testosterone increases mortality risk among male dialysis patients. J. Am. Soc. Nephrol. 20, 613–620 (2009).
- 65
Carrero, J. J. et al. Testosterone deficiency is a cause of anaemia and reduced responsiveness to erythropoiesis-stimulating agents in men with chronic kidney disease. Nephrol. Dial. Transplant. 27, 709–715 (2012).
- 66
Bello, A. K. et al. Serum testosterone levels and clinical outcomes in male hemodialysis patients. Am. J. Kidney Dis. 63, 268–275 (2014).
- 67
Weisinger, J. R. & Bellorin-Font, E. Outcomes associated with hypogonadism in women with chronic kidney disease. Adv. Chronic Kidney Dis. 11, 361–370 (2004).
- 68
Couchoud, C. et al. From registry data collection to international comparisons: examples of haemodialysis duration and frequency. Nephrol. Dial. Transplant. 24, 217–224 (2009).
- 69
Daugirdas, J. T. et al. Surface-area-normalized Kt/V: a method of rescaling dialysis dose to body surface area-implications for different-size patients by gender. Semin. Dial. 21, 415–421 (2008).
- 70
Spalding, E. M., Chandna, S. M., Davenport, A. & Farrington, K. Kt/V underestimates the hemodialysis dose in women and small men. Kidney Int. 74, 348–355 (2008).
- 71
Eknoyan, G. et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N. Engl. J. Med. 347, 2010–2019 (2002).
- 72
Depner, T. et al. Dialysis dose and the effect of gender and body size on outcome in the HEMO Study. Kidney Int. 65, 1386–1394 (2004).
- 73
Port, F. K. et al. High dialysis dose is associated with lower mortality among women but not among men. Am. J. Kidney Dis. 43, 1014–1023 (2004).
- 74
Daugirdas, J. T., Greene, T., Chertow, G. M. & Depner, T. A. Can rescaling dose of dialysis to body surface area in the HEMO study explain the different responses to dose in women versus men? Clin. J. Am. Soc. Nephrol. 5, 1628–1636 (2010).
- 75
Noordzij, M. et al. Use of vascular access for haemodialysis in Europe: a report from the ERA-EDTA Registry. Nephrol. Dial. Transplant. 29, 1956–1964 (2014).
- 76
Caplin, N., Sedlacek, M., Teodorescu, V., Falk, A. & Uribarri, J. Venous access: women are equal. Am. J. Kidney Dis. 41, 429–432 (2003).
- 77
Vogelzang, J. L. et al. Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry. Nephrol. Dial. Transplant. 30, 1028–1037 (2015).
- 78
Ifudu, O. Patient characteristics determining rHuEPO dose requirements. Nephrol. Dial. Transplant. 17 (Suppl. 5), 38–41 (2002).
- 79
Hsu, C. Y., Bates, D. W., Kuperman, G. J. & Curhan, G. C. Relationship between hematocrit and renal function in men and women. Kidney Int. 59, 725–731 (2001).
- 80
Hsu, C. Y., McCulloch, C. E. & Curhan, G. C. Epidemiology of anemia associated with chronic renal insufficiency among adults in the United States: results from the Third National Health and Nutrition Examination Survey. J. Am. Soc. Nephrol. 13, 504–510 (2002).
- 81
Ferrucci, L. et al. Low testosterone levels and the risk of anemia in older men and women. Arch. Intern. Med. 166, 1380–1388 (2006).
- 82
Group, K. D. I. G. O. K. A. W. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int. Suppl. 2, 279–335 (2012).
- 83
Locatelli, F. et al. Clinical practice guidelines for anemia in chronic kidney disease: problems and solutions. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 74, 1237–1240 (2008).
- 84
Frankenfield, D. L. et al. Racial/ethnic analysis of selected intermediate outcomes for hemodialysis patients: results from the 1997 ESRD Core Indicators Project. Am. J. Kidney Dis. 34, 721–730 (1999).
- 85
Madore, F. et al. Anemia in hemodialysis patients: variables affecting this outcome predictor. J. Am. Soc. Nephrol. 8, 1921–1929 (1997).
- 86
Ifudu, O. et al. Gender modulates responsiveness to recombinant erythropoietin. Am. J. Kidney Dis. 38, 518–522 (2001).
- 87
Kjellstrand, C. M. Age, sex, and race inequality in renal transplantation. Arch. Intern. Med. 148, 1305–1309 (1988).
- 88
Held, P. J., Pauly, M. V., Bovbjerg, R. R., Newmann, J. & Salvatierra, O. Jr. Access to kidney transplantation. Has the United States eliminated income and racial differences? Arch. Intern. Med. 148, 2594–2600 (1988).
- 89
Eggers, P. W. Effect of transplantation on the Medicare end-stage renal disease program. N. Engl. J. Med. 318, 223–229 (1988).
- 90
Alexander, G. C. & Sehgal, A. R. Barriers to cadaveric renal transplantation among blacks, women, and the poor. JAMA 280, 1148–1152 (1998).
- 91
Gaylin, D. S. et al. The impact of comorbid and sociodemographic factors on access to renal transplantation. JAMA 269, 603–608 (1993).
- 92
Soucie, J. M., Neylan, J. F. & McClellan, W. Race and sex differences in the identification of candidates for renal transplantation. Am. J. Kidney Dis. 19, 414–419 (1992).
- 93
Bloembergen, W. E., Mauger, E. A., Wolfe, R. A. & Port, F. K. Association of gender and access to cadaveric renal transplantation. Am. J. Kidney Dis. 30, 733–738 (1997).
- 94
Schaubel, D. E. et al. Sex inequality in kidney transplantation rates. Arch. Intern. Med. 160, 2349–2354 (2000).
- 95
Segev, D. L. et al. Age and comorbidities are effect modifiers of gender disparities in renal transplantation. J. Am. Soc. Nephrol. 20, 621–628 (2009).
- 96
Wolfe, R. A. et al. Differences in access to cadaveric renal transplantation in the United States. Am. J. Kidney Dis. 36, 1025–1033 (2000).
- 97
Kayler, L. K. et al. Gender imbalance in living donor renal transplantation. Transplantation 73, 248–252 (2002).
- 98
Kayler, L. K. et al. Gender imbalance and outcomes in living donor renal transplantation in the United States. Am. J. Transplant. 3, 452–458 (2003).
- 99
Ojo, A. & Port, F. K. Influence of race and gender on related donor renal transplantation rates. Am. J. Kidney Dis. 22, 835–841 (1993).
- 100
Bloembergen, W. E., Port, F. K., Mauger, E. A., Briggs, J. P. & Leichtman, A. B. Gender discrepancies in living related renal transplant donors and recipients. J. Am. Soc. Nephrol. 7, 1139–1144 (1996).
- 101
Roodnat, J. I. et al. Accumulation of unfavorable clinical and socioeconomic factors precludes living donor kidney transplantation. Transplantation 93, 518–523 (2012).
- 102
Zimmerman, D., Donnelly, S., Miller, J., Stewart, D. & Albert, S. E. Gender disparity in living renal transplant donation. Am. J. Kidney Dis. 36, 534–540 (2000).
- 103
Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients. OPTN/SRTR 2012 annual data report (OPTN/SRTR, 2014).
- 104
Rodrigue, J. R. et al. Living donor kidney transplantation: overcoming disparities in live kidney donation in the US — recommendations from a consensus conference. Clin. J. Am. Soc. Nephrol. 10, 1687–1695 (2015).
- 105
Simmons, R. & Klein, S. The Social and Psychological Impact of Organ Transplantation (Wiley, 1977).
- 106
Khalifeh, N. & Horl, W. H. Gender and living donor kidney transplantation. Wien. Med. Wochenschr. 161, 124–127 (2011).
- 107
Carrero, J. J., Hecking, M., Ulasi, I., Sola, L. & Thomas, B. Chronic kidney disease, gender, and access to care: a global perspective. Semin. Nephrol. 37, 296–308 (2017).
- 108
Jindal, R. M., Ryan, J. J., Sajjad, I., Murthy, M. H. & Baines, L. S. Kidney transplantation and gender disparity. Am. J. Nephrol. 25, 474–483 (2005).
- 109
Liu, G. et al. Gender disparity of living donor renal transplantation in East China. Clin. Transplant 27, 98–103 (2013).
- 110
Soliman, Y., Shawky, S., Khedr, A.-E., Hassan, A. M. & Behairy, M. Incidence of acute renal allograft rejection in egyptian renal transplant recipients: a single center experience. Life Sci. J. 12, 9–15 (2015).
- 111
Bal, M. M. & Saikia, B. Gender bias in renal transplantation: are women alone donating kidneys in India? Transplant. Proc. 39, 2961–2963 (2007).
- 112
Ramachandran, R. & Jha, V. Kidney transplantation is associated with catastrophic out of pocket expenditure in India. PLoS ONE 8, e67812 (2013).
- 113
Ghods, A. J. & Nasrollahzadeh, D. Gender disparity in a live donor renal transplantation program: assessing from cultural perspectives. Transplant. Proc. 35, 2559–2560 (2003).
- 114
Khajehdehi, P. Living non-related versus related renal transplantation—its relationship to the social status, age and gender of recipients and donors. Nephrol. Dial. Transplant. 14, 2621–2624 (1999).
- 115
Malakoutian, T. et al. Socioeconomic status of Iranian living unrelated kidney donors: a multicenter study. Transplant. Proc. 39, 824–825 (2007).
- 116
Naghibi, O., Naghibi, M. & Nazemian, F. Gender disparity in kidney transplantation. Saudi J. Kidney Dis. Transpl. 19, 545–550 (2008).
- 117
Kwon, O. J. & Kwak, J. Y. The impact of sex and age matching for long-term graft survival in living donor renal transplantation. Transplant. Proc. 36, 2040–2042 (2004).
- 118
Chalise, P. R. et al. Renal transplantation in Nepal: the first year's experience. Saudi J. Kidney Dis. Transpl. 21, 559–564 (2010).
- 119
Arogundade, F. A. Kidney transplantation in a low-resource setting: Nigeria experience. Kidney Int. Suppl. (2011) 3, 241–245 (2013).
- 120
Shaheen, F. A. et al. Experience of renal transplantation at the king fahd hospital, jeddah, saudi arabia. Saudi J. Kidney Dis. Transpl. 16, 562–572 (2005).
- 121
Bardi, R. et al. Kidney transplantation: Charles Nicolle Hospital experience. Transplant. Proc. 41, 651–653 (2009).
- 122
Peracha, J., Hayer, M. K. & Sharif, A. Gender disparity in living-donor kidney transplant among minority ethnic groups. Exp. Clin. Transplant. 14, 139–145 (2016).
- 123
Biller-Andorno, N. Gender imbalance in living organ donation. Med. Health Care Philos. 5, 199–204 (2002).
- 124
Goryainov, V. A. et al. [The effect of gender on the results of related kidney transplantation]. Khirurgiia (Mosk) https://doi.org/10.17116/hirurgia2016662-67 (in Russian) (2016).
- 125
Thiel, G. T., Nolte, C. & Tsinalis, D. Gender imbalance in living kidney donation in Switzerland. Transplant. Proc. 37, 592–594 (2005).
- 126
Noppakun, K. et al. A 25-year experience of kidney transplantation in Thailand: report from the Thai transplant registry. Nephrol. (Carlton) 20, 177–183 (2015).
- 127
Barsky, A. J., Peekna, H. M. & Borus, J. F. Somatic symptom reporting in women and men. J. Gen. Intern. Med. 16, 266–275 (2001).
- 128
H.Åvard Loge, J. & Kaasa, S. Short Form 36 (SF-36) health survey: normative data from the general Norwegian population. Scand. J. Social Med. 26, 250–258 (2016).
- 129
Ong, L. et al. Gender differences and quality of life in atrial fibrillation: the mediating role of depression. J. Psychosom. Res. 61, 769–774 (2006).
- 130
Vigneshwaran, E., Padmanabhareddy, Y., Devanna, N. & Alvarez-Uria, G. Gender differences in health related quality of life of people living with HIV/AIDS in the era of highly active antiretroviral therapy. N. Am. J. Med. Sci. 5, 102–107 (2013).
- 131
Liu, W. J., Chew, T. F., Chiu, A. S. & Zaki, M. Quality of life of dialysis patients in Malaysia. Med. J. Malaysia 61, 540–546 (2006).
- 132
Germin-Petrovic, D. et al. Health-related quality of life in the patients on maintenance hemodialysis: the analysis of demographic and clinical factors. Coll. Antropol. 35, 687–693 (2011).
- 133
Kutner, N. G., Zhang, R. & Brogan, D. Race, gender, and incident dialysis patients' reported health status and quality of life. J. Am. Soc. Nephrol. 16, 1440–1448 (2005).
- 134
Vazquez, I. et al. [Differences in health-related quality of life between male and female hemodialysis patients]. Nefrologia 24, 167–178 (2004).
- 135
Lopes, A. A. et al. Factors associated with health-related quality of life among hemodialysis patients in the DOPPS. Qual. Life Res. 16, 545–557 (2007).
- 136
Poulsen, C. G., Kjaergaard, K. D., Peters, C. D., Jespersen, B. & Jensen, J. D. Quality of life development during initial hemodialysis therapy and association with loss of residual renal function. Hemodial. Int. 21, 409–421 (2017).
- 137
Wight, J. P. et al. The SF36 as an outcome measure of services for end stage renal failure. Qual. Health Care 7, 209–221 (1998).
- 138
Molarius, A. & Janson, S. Self-rated health, chronic diseases, and symptoms among middle-aged and elderly men and women. J. Clin. Epidemiol. 55, 364–370 (2002).
- 139
Almutary, H., Bonner, A. & Douglas, C. Which patients with chronic kidney disease have the greatest symptom burden? A comparative study of advanced cKD stage and dialysis modality. 42, 73–82 (2016).
- 140
Weisbord, S. D. et al. Prevalence, severity, and importance of physical and emotional symptoms in chronic hemodialysis patients. J. Am. Soc. Nephrol. 16, 2487–2494 (2005).
- 141
Caplin, B., Kumar, S. & Davenport, A. Patients' perspective of haemodialysis-associated symptoms. Nephrol. Dial. Transplant. 26, 2656–2663 (2011).
- 142
Lopes, G. B. et al. Depression as a potential explanation for gender differences in health-related quality of life among patients on maintenance hemodialysis. Nephron Clin. Pract. 115, c35–c40 (2010).
- 143
Overbeck, I. et al. Changes in quality of life after renal transplantation. Transplant. Proc. 37, 1618–1621 (2005).
- 144
Fiebiger, W., Mitterbauer, C. & Oberbauer, R. Health-related quality of life outcomes after kidney transplantation. Health Qual. Life Outcomes 2, 2 (2004).
- 145
von der Lippe, N., Waldum, B., Osthus, T. B., Reisaeter, A. V. & Os, I. Health related quality of life in patients in dialysis after renal graft loss and effect of gender. BMC Womens Health 14, 34 (2014).
- 146
Weissman, M. M. et al. Cross-national epidemiology of major depression and bipolar disorder. JAMA 276, 293–299 (1996).
- 147
Abdel-Kader, K., Unruh, M. L. & Weisbord, S. D. Symptom burden, depression, and quality of life in chronic and end-stage kidney disease. Clin. J. Am. Soc. Nephrol. 4, 1057–1064 (2009).
- 148
Norris, C. M., Hegadoren, K. & Pilote, L. Depression symptoms have a greater impact on the 1-year health-related quality of life outcomes of women post-myocardial infarction compared to men. Eur. J. Cardiovasc. Nurs. 6, 92–98 (2007).
- 149
Lernmark, B., Persson, B., Fisher, L. & Rydelius, P. A. Symptoms of depression are important to psychological adaptation and metabolic control in children with diabetes mellitus. Diabet. Med. 16, 14–22 (1999).
- 150
La Greca, A. M., Swales, T., Klemp, S., Madigan, S. & Skyler, J. Adolescents with diabetes: gender differences in psychosocial functioning and glycemic control. Children's Health Care 24, 61–78 (1995).
- 151
Yeh, S. C. & Chou, H. C. Coping strategies and stressors in patients with hemodialysis. Psychosom. Med. 69, 182–190 (2007).
- 152
Yeh, S. C. J., Huang, C. H., Chou, H. C. & Wan, T. T. H. Gender differences in stress and coping among elderly patients on hemodialysis. Sex Roles 60, 44–56 (2009).
- 153
Tu, H. Y., Shao, J. H., Wu, F. J., Chen, S. H. & Chuang, Y. H. Stressors and coping strategies of 20–45-year-old hemodialysis patients. Collegian 21, 185–192 (2014).
- 154
Lindqvist, R., Carlsson, M. & Sjoden, P. O. Coping strategies and quality of life among patients on hemodialysis and continuous ambulatory peritoneal dialysis. Scand. J. Caring Sci. 12, 223–230 (1998).
- 155
Mendes de Leon, C. F. et al. Psychosocial characteristics after acute myocardial infarction: the ENRICHD pilot study. Enhancing Recovery in Coronary Heart Disease. J. Cardiopulm. Rehabil. 21, 353–362 (2001).
- 156
Norris, C. M. et al. Women with coronary artery disease report worse health-related quality of life outcomes compared to men. Health Qual. Life Outcomes 2, 21 (2004).
- 157
Yan, G. et al. Race/ethnicity, age, and risk of hospital admission and length of stay during the first year of maintenance hemodialysis. Clin. J. Am. Soc. Nephrol. 9, 1402–1409 (2014).
- 158
Adams, S. V. et al. Sex differences in hospitalizations with maintenance hemodialysis. J. Am. Soc. Nephrol. 28, 2721–2728 (2017).
- 159
Dalrymple, L. S. et al. Infection-related hospitalizations in older patients with ESRD. Am. J. Kidney Dis. 56, 522–530 (2010).
- 160
Dalrymple, L. S. et al. Outcomes of infection-related hospitalization in Medicare beneficiaries receiving in-center hemodialysis. Am. J. Kidney Dis. 65, 754–762 (2015).
- 161
Newman, K. L. et al. Hospitalization among individuals waitlisted for kidney transplant. Transplantation. 101, 2913–2923 (2017).
- 162
Manteuffel, M. et al. Influence of patient sex and gender on medication use, adherence, and prescribing alignment with guidelines. J. Womens Health (Larchmt) 23, 112–119 (2014).
- 163
Carrero, J. J. et al. Cardiovascular and noncardiovascular mortality among men and women starting dialysis. Clin. J. Am. Soc. Nephrol. 6, 1722–1730 (2011).
- 164
Ros, S. et al. Increased risk of fatal infections in women starting peritoneal dialysis. Perit. Dial. Int. 33, 487–494 (2013).
- 165
Koo, J. H. & Leong, R. W. Sex differences in epidemiological, clinical and pathological characteristics of colorectal cancer. J. Gastroenterol. Hepatol. 25, 33–42 (2010).
- 166
Molife, R., Lorigan, P. & MacNeil, S. Gender and survival in malignant tumours. Cancer Treat. Rev. 27, 201–209 (2001).
- 167
Ellwood, A. D. et al. Early dialysis initiation and rates and timing of withdrawal from dialysis in Canada. Clin. J. Am. Soc. Nephrol. 8, 265–270 (2013).
- 168
Chan, H. W., Clayton, P. A., McDonald, S. P., Agar, J. W. & Jose, M. D. Risk factors for dialysis withdrawal: an analysis of the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, 1999–2008. Clin. J. Am. Soc. Nephrol. 7, 775–781 (2012).
- 169
Terasaki, P. I., Cecka, J. M., Gjertson, D. W. & Takemoto, S. High survival rates of kidney transplants from spousal and living unrelated donors. N. Engl. J. Med. 333, 333–336 (1995).
- 170
Sanfilippo, F., Vaughn, W. K., Bollinger, R. R. & Spees, E. K. Comparative effects of pregnancy, transfusion, and prior graft rejection on sensitization and renal transplant results. Transplantation 34, 360–366 (1982).
- 171
Iwaki, Y. & Terasaki, P. I. Sensitization effect. Clin. Transpl. 257–265 (1986).
- 172
Bohmig, G. A. et al. Role of humoral immune reactions as target for antirejection therapy in recipients of a spousal-donor kidney graft. Am. J. Kidney Dis. 35, 667–673 (2000).
- 173
Halloran, P. F., Schlaut, J., Solez, K. & Srinivasa, N. S. The significance of the anti-class I response. II. Clinical and pathologic features of renal transplants with anti-class I-like antibody. Transplantation 53, 550–555 (1992).
- 174
Terasaki, P. I. Humoral theory of transplantation. Am. J. Transplant. 3, 665–673 (2003).
- 175
Geneugelijk, K. et al. Predicted indirectly recognizable HLA epitopes presented by HLA-DRB1 are related to HLA antibody formation during pregnancy. Am. J. Transplant. 15, 3112–3122 (2015).
- 176
Honger, G. et al. Frequency and determinants of pregnancy-induced child-specific sensitization. Am. J. Transplant. 13, 746–753 (2013).
- 177
Bromberger, B. et al. Pregnancy-induced sensitization promotes sex disparity in living donor kidney transplantation. J. Am.Soc.Nephrol. 28, 3025–3033 (2017).
- 178
Burlingham, W. J. et al. The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors. N. Engl. J. Med. 339, 1657–1664 (1998).
- 179
Claas, F. H., Gijbels, Y., van der Velden-de Munck, J. & van Rood, J. J. Induction of B cell unresponsiveness to noninherited maternal HLA antigens during fetal life. Science 241, 1815–1817 (1988).
- 180
Owen, R. D., Wood, H. R., Foord, A. G., Sturgeon, P. & Baldwin, L. G. Evidence for actively acquired tolerance to Rh antigens. Proc. Natl Acad. Sci. USA 40, 420–424 (1954).
- 181
Lim, W. H. et al. Maternal compared with paternal donor kidneys are associated with poorer graft outcomes after kidney transplantation. Kidney Int. 89, 659–665 (2016).
- 182
Lepeytre, F. et al. Association of sex with risk of kidney graft failure differs by age. J. Am. Soc. Nephrol. 28, 3014–3023 (2017).
- 183
Pfeffer, P. F. & Thorsby, E. HLA-restricted cytotoxicity against male-specific (H-Y) antigen after acute rejection of an HLA-identical sibling kidney: clonal distribution of the cytotoxic cells. Transplantation 33, 52–56 (1982).
- 184
Tan, J. C. et al. H-Y antibody development associates with acute rejection in female patients with male kidney transplants. Transplantation 86, 75–81 (2008).
- 185
Popli, R., Sahaf, B., Nakasone, H., Lee, J. Y. & Miklos, D. B. Clinical impact of H-Y alloimmunity. Immunol. Res. 58, 249–258 (2014).
- 186
Giefing-Kroll, C., Berger, P., Lepperdinger, G. & Grubeck-Loebenstein, B. How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging Cell 14, 309–321 (2015).
- 187
Bouman, A., Heineman, M. J. & Faas, M. M. Sex hormones and the immune response in humans. Hum. Reprod. Update 11, 411–423 (2005).
- 188
Fish, E. N. The X-files in immunity: sex-based differences predispose immune responses. Nat. Rev. Immunol. 8, 737–744 (2008).
- 189
Feldman, H. I. et al. Recipient body size and cadaveric renal allograft survival. J. Am. Soc. Nephrol. 7, 151–157 (1996).
- 190
Oh, C. K. et al. Metabolic demand and renal mass supply affecting the early graft function after living donor kidney transplantation. Kidney Int. 67, 744–749 (2005).
- 191
Denhaerynck, K. et al. Prevalence and risk factors of non-adherence with immunosuppressive medication in kidney transplant patients. Am. J. Transplant. 7, 108–116 (2007).
- 192
Frazier, P. A., Davis-Ali, S. H. & Dahl, K. E. Correlates of noncompliance among renal transplant recipients. Clin. Transplant. 8, 550–557 (1994).
- 193
Kiley, D. J., Lam, C. S. & Pollak, R. A study of treatment compliance following kidney transplantation. Transplantation 55, 51–56 (1993).
- 194
Stringer, K. D. et al. Gender hormones and the progression of experimental polycystic kidney disease. Kidney Int. 68, 1729–1739 (2005).
- 195
Elliot, S. J. et al. Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis. Kidney Int. 72, 464–472 (2007).
- 196
Maric, C., Sandberg, K. & Hinojosa-Laborde, C. Glomerulosclerosis and tubulointerstitial fibrosis are attenuated with 17beta-estradiol in the aging Dahl salt sensitive rat. J. Am. Soc. Nephrol. 15, 1546–1556 (2004).
- 197
Catanuto, P. et al. 17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes. Kidney Int. 75, 1194–1201 (2009).
- 198
Hutchens, M. P., Fujiyoshi, T., Komers, R., Herson, P. S. & Anderson, S. Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo. Am. J. Physiol. Renal Physiol. 303, F377–F385 (2012).
- 199
Metcalfe, P. D. et al. Testosterone exacerbates obstructive renal injury by stimulating TNF-alpha production and increasing proapoptotic and profibrotic signaling. Am. J. Physiol. Endocrinol. Metab. 294, E435–E443 (2008).
- 200
Reckelhoff, J. F., Zhang, H. & Srivastava, K. Gender differences in development of hypertension in spontaneously hypertensive rats: role of the renin-angiotensin system. Hypertension 35, 480–483 (2000).
- 201
Filler, G. et al. Is Testosterone Detrimental to Renal Function?. Kidney Int. Rep. 1, 306–310 (2016).
- 202
Baylis, C. & Corman, B. The aging kidney: insights from experimental studies. J. Am. Soc. Nephrol. 9, 699–709 (1998).
- 203
Monster, T. B., Janssen, W. M., de Jong, P. E., de Jong-van den Berg, L. T. & Prevention of Renal and Vascular End Stage Disease Study Group. Oral contraceptive use and hormone replacement therapy are associated with microalbuminuria. Arch. Intern. Med. 161, 2000–2005 (2001).
- 204
Ahmed, S. B. et al. Oral estrogen therapy in postmenopausal women is associated with loss of kidney function. Kidney Int. 74, 370–376 (2008).
- 205
Yilmaz, M.I. et al. Endogenous testosterone, endothelial dysfunction, and cardiovascular events in men with nondialysis cronic kidney disease. Clin. J. Am. Soc. Nephrol. 6, 1617–1625 (2011).
- 206
Haring, R. et al. Low serum testosterone is associated with increased mortality in men with stage 3 or greater nephropathy. Am. J. Nephrol. 33, 209–217 (2011).
- 207
Khurana, K. K. et al. Serum testosterone levels and mortality in men with CKD stages 3–4. Am. J. Kidney Dis. 64, 367–374 (2014).
- 208
Lapi, F. et al. Androgen deprivation therapy and risk of acute kidney injury in patients with prostate cancer. Jama 310, 289–296 (2013).
- 209
Neugarten, J., Gallo, G., Silbiger, S. & Kasiske, B. Glomerulosclerosis in aging humans is not influenced by gender. Am. J. Kidney Dis. 34, 884–888 (1999).
- 210
Baylis, C. Sexual dimorphism in the aging kidney: differences in the nitric oxide system. Nat. Rev. Nephrol. 5, 384–396 (2009).
- 211
Baylis, C. Sexual dimorphism: the aging kidney, involvement of nitric oxide deficiency, and angiotensin II overactivity. J. Gerontol. A Biol. Sci. Med. Sci. 67, 1365–1372 (2012).
- 212
Matsuda, T., Yamamoto, T., Muraguchi, A. & Saatcioglu, F. Cross-talk between transforming growth factor-beta and estrogen receptor signaling through Smad3. J. Biol. Chem. 276, 42908–42914 (2001).
- 213
Moxley, G. et al. Premenopausal sexual dimorphism in lipopolysaccharide-stimulated production and secretion of tumor necrosis factor. J. Rheumatol. 31, 686–694 (2004).
- 214
Ji, H. et al. Female protection in progressive renal disease is associated with estradiol attenuation of superoxide production. Gend. Med. 4, 56–71 (2007).
- 215
Agondi, R. e. F., Gallani, M. C., Rodrigues, R. C. & Cornélio, M. E. Relationship between beliefs regarding a low salt diet in chronic renal failure patients on dialysis. J. Ren. Nutr. 21, 160–168 (2011).
- 216
Crews, D. C. et al. Dietary habits, poverty, and chronic kidney disease in an urban population. J. Ren. Nutr. 25, 103–110 (2015).
- 217
Ellam, T., Fotheringham, J. & Kawar, B. Differential scaling of glomerular filtration rate and ingested metabolic burden: implications for gender differences in chronic kidney disease outcomes. Nephrol. Dial Transplant 29, 1186–1194 (2014).
- 218
Nitsch, D. Is there a difference in metabolic burden between men and women? Nephrol. Dial. Transplant. 29, 1110–1112 (2014).
- 219
Verhave, J. C. et al. Cardiovascular risk factors are differently associated with urinary albumin excretion in men and women. J. Am. Soc. Nephrol. 14, 1330–1335 (2003).
- 220
Coggins, C. H. et al. Differences between women and men with chronic renal disease. Nephrol. Dial. Transplant. 13, 1430–1437 (1998).
- 221
Williams, D. & Davison, J. Chronic kidney disease in pregnancy. BMJ 336, 211–215 (2008).
- 222
Dehmer, E. W. et al. Association between gestational diabetes and incident maternal CKD: the Coronary Artery Risk Development in Young Adults (CARDIA) study. https://doi.org/10.1053/j.ajkd.2017.08.015 (2017).
Acknowledgements
The authors thank P. Trocchi (Universitätsklinikum Essen, Germany) for providing sex-specific statistics from Germany and F. K. Port (Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA), as well as T. Stamm, G. Böhmig and G. Bond (all from Medical University of Vienna, Austria) for their helpful comments and revisions to this work. J.J.C. acknowledges grant support from the Swedish Heart and Lung Foundation and the Westman and Rind foundations. N.C.C. and K.J.J. acknowledge grant support from the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA).
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Glossary
- Kt/V
-
The preferred method for measuring the dialysis dose; defined as the dialyser clearance of urea (K) multiplied by the duration of the dialysis treatment (t, in minutes) divided by the volume of distribution of urea in the body (V, in ml), which is approximately equal to total body water, corrected for volume lost during ultrafiltration.
- Prevalent dialysis patients
-
All patients treated by dialysis at a particular moment in time.
- Incident dialysis patients
-
Patients starting dialysis for the first time.
- HLA sensitization
-
Formation of alloantibodies against HLA antigens.
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Carrero, J., Hecking, M., Chesnaye, N. et al. Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease. Nat Rev Nephrol 14, 151–164 (2018). https://doi.org/10.1038/nrneph.2017.181
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