Advertisement

The Other Way Around: Living With Chronic Kidney Disease From the Perspective of Men

      Summary

      A wealth of evidence has suggested sex (biological) and gender (sociocultural) differences in the prevalence, progression, and outcomes of persons with chronic kidney disease. Much of this evidence tends to emphasize differences in which women are disadvantaged, and less attention is paid to findings in which women are better off or similar to men. However, gender medicine recognizes that men and women have different disease determinants, presentation, and attitudes, and it pertains to both sexes. In this review, we revisit chronic kidney disease through the perspective of men, and illustrate a population segment at need of stringent preventative and management strategies.

      Keywords

      The past 2 decades have evidenced the prominent role of sex (biological constructs) and gender (social constructs) as modifiers of the most common causes of death and morbidity in society.
      • Mauvais-Jarvis F
      • Bairey Merz N
      • Barnes PJ
      • et al.
      Sex and gender: modifiers of health, disease, and medicine.
      ,
      • Mauvais-Jarvis F
      • Berthold HK
      • Campesi I
      • et al.
      Sex- and gender-based pharmacological response to drugs.
      Chronic kidney disease (CKD) is no exception because men and women, males and females, experience notable differences in its prevalence, progression, and outcomes.
      • Carrero JJ
      • Hecking M
      • Chesnaye NC
      • Jager KJ.
      Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease.
      Gender medicine represents a pivotal platform for nephrologists to better address the needs of their patients within the framework of precision medicine. However, it is a field of knowledge in which implementation practices still are not generalized.
      Much of the evidence to date, as also summarized in this issue of Seminars in Nephrology, tends to emphasize differences in which women are disadvantaged. Identifying such gender disparity is an important area that requires both clinical and research efforts and that has been the subject of our previous work.
      • Carrero JJ
      • Hecking M
      • Chesnaye NC
      • Jager KJ.
      Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease.
      • Carrero JJ
      • Hecking M
      • Ulasi I
      • Sola L
      • Thomas B.
      Chronic kidney disease, gender, and access to care: a global perspective.
      • Cobo G
      • Hecking M
      • Port FK
      • et al.
      Sex and gender differences in chronic kidney disease: progression to end-stage renal disease and haemodialysis.
      • Carrero JJ.
      Gender differences in chronic kidney disease: underpinnings and therapeutic implications.
      However, less attention is paid to findings in which women are better off or similar to men. Perhaps because of the publish or perish pressure of academia, favorable and statistically significant findings are more likely to be published.
      • Canestaro WJ
      • Hendrix N
      • Bansal A
      • Sullivan SD
      • Devine EB
      • Carlson JJ.
      Favorable and publicly funded studies are more likely to be published: a systematic review and meta-analysis.
      This publication bias may provide a partial view of the problem.
      Gender medicine recognizes that men and women have different determinants and presentation of disease, and aims to improve the disease experience of both sexes. We propose in this review to revisit various aspects of CKD through the perspective of men, illustrating a population segment at need of stringent preventative and management strategies. We recognize, however, that in many of the studies listed, it is not possible to differentiate the effects of sex from those of gender, for example, different countries, cultures, and socioeconomic positions allow for differential access to care.

      FACT 1: THE PROGRESSION TO END-STAGE KIDNEY DISEASE IS FASTER IN MEN

      Probably because of faster progression to kidney failure in men (discussed later), a higher risk of premature death in men, and the longer life expectancy of women, the lifetime risk of developing CKD stage 3 is reportedly higher in men than for women.
      • Grams ME
      • Chow EK
      • Segev DL
      • Coresh J.
      Lifetime incidence of CKD stages 3-5 in the United States.
      ,
      • Inker LA
      • Tighiouart H
      • Aspelund T
      • et al.
      Lifetime risk of stage 3-5 CKD in a community-based sample in Iceland.
      Despite wide geographic variation, there are more women than men in society with nondialysis CKD stages 3 to 5.
      • Carrero JJ
      • Hecking M
      • Chesnaye NC
      • Jager KJ.
      Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease.
      However, the majority of individuals who progress to kidney failure or undergo maintenance dialysis/transplantation are men.
      • Hecking M
      • Bieber BA
      • Ethier J
      • 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).
      • Antlanger M
      • Noordzij M
      • van de Luijtgaarden M
      • et al.
      Sex differences in kidney replacement therapy initiation and maintenance.
      • Kainz A
      • Berner C
      • Ristl R
      • et al.
      Sex-specific analysis of haemodialysis prevalence, practices and mortality over time: the Austrian Dialysis Registry from 1965 to 2014.
      • Carrero JJ
      • de Jager DJ
      • Verduijn M
      • et al.
      Cardiovascular and noncardiovascular mortality among men and women starting dialysis.
      Although not always a universal finding in historical literature,
      • Neugarten J
      • Acharya A
      • Silbiger SR.
      Effect of gender on the progression of nondiabetic renal disease: a meta-analysis.
      ,
      • Jafar TH
      • Schmid CH
      • Stark PC
      • et al.
      The rate of progression of renal disease may not be slower in women compared with men: a patient-level meta-analysis.
      there is agreement that the loss of kidney function over time and progression to kidney failure occurs more rapidly in men.
      • Neugarten J
      • Golestaneh L.
      Influence of sex on the progression of chronic kidney disease.
      • Minutolo R
      • Gabbai FB
      • Chiodini P
      • et al.
      Sex differences in the progression of CKD among older patients: pooled analysis of 4 cohort studies.
      • Swartling O
      • Rydell H
      • Stendahl M
      • Segelmark M
      • Trolle Lagerros Y
      • Evans M
      CKD progression and mortality among men and women: a nationwide study in Sweden.
      For example, a recent analysis from the chronic renal insufficiency cohort (CRIC)
      • Ricardo AC
      • Yang W
      • Sha D
      • et al.
      Sex-related disparities in CKD progression.
      showed that, compared with women, men had a 17% higher risk of starting dialysis, as well as a steeper mean unadjusted estimated glomerular filtration rate (eGFR) slope (-1.43 mL/min per 1.73 m2 versus -1.09 mL/min per 1.73 m2 per year in women). Interestingly, differences in eGFR slope disappeared after adjustment for lifestyle factors and comorbidities, which opens the hypothesis to modifiable factors haltering CKD progression in men.
      Recently, and using data from 888 children, Bonneric et al
      • Bonneric S
      • Karadkhele G
      • Couchoud C
      • Patzer RE
      • Greenbaum LA
      • Hogan J.
      Sex and glomerular filtration rate trajectories in children.
      explored possible differences in eGFR trajectories and the risk of CKD progression between sexes. In children with nonglomerular diseases, males had a faster CKD progression, but again the sex effect was not significant after multivariable adjustment. In children with glomerular diseases, females had faster CKD progression. Thus, underlying primary kidney disease (which for some etiologies also is sex-specific) may result in different progression rates between sexes. Although historical evidence was generated previously on this phenomenon (eg, in diabetic nephropathy), it is a reminder that kidney diseases are complex and all etiologies cannot be oversimplified to a single eGFR.
      Underlying mechanisms for faster progression in men are not well elucidated. On the one hand, animal studies attribute these differences to deleterious effects of testosterone.
      • Elliot SJ
      • Berho M
      • Korach K
      • et al.
      Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis.
      • Metcalfe PD
      • Leslie JA
      • Campbell MT
      • Meldrum DR
      • Hile KL
      • Meldrum KK.
      Testosterone exacerbates obstructive renal injury by stimulating TNF-alpha production and increasing proapoptotic and profibrotic signaling.
      • Reckelhoff JF
      • Zhang H
      • Srivastava K.
      Gender differences in development of hypertension in spontaneously hypertensive rats: role of the renin-angiotensin system.
      However, this causality is difficult to reconcile with literature regarding the association between testosterone deficiency and adverse clinical outcomes in men with CKD, and the role of testosterone replacement therapy on managing complications of CKD such as anemia or muscle wasting.
      • Carrero JJ.
      Testosterone deficiency at the crossroads of cardiometabolic complications in CKD.
      ,
      • Carrero JJ
      • Stenvinkel P.
      The vulnerable man: impact of testosterone deficiency on the uraemic phenotype.
      Other animal studies have reported that although nitric oxide production is lower in male compared with female animals,
      • Baylis C.
      Sexual dimorphism in the aging kidney: differences in the nitric oxide system.
      proinflammatory mediators of kidney injury
      • Matsuda T
      • Yamamoto T
      • Muraguchi A
      • Saatcioglu F.
      Cross-talk between transforming growth factor-beta and estrogen receptor signaling through Smad3.
      ,
      • Moxley G
      • Stern AG
      • Carlson P
      • Estrada E
      • Han J
      • Benson LL.
      Premenopausal sexual dimorphism in lipopolysaccharide-stimulated production and secretion of tumor necrosis factor.
      and oxidative stress in the kidney are higher.
      • Ji H
      • Zheng W
      • Menini S
      • et al.
      Female protection in progressive renal disease is associated with estradiol attenuation of superoxide production.
      On the other hand, faster progression rates in men may be attributed to more unhealthy behaviors. Men with CKD are described as eating more and more unhealthily than their female counterparts, thereby presenting with a higher metabolic burden that may accelerate eGFR decline.
      • 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.
      • Nitsch D.
      Is there a difference in metabolic burden between men and women?.
      • Gutierrez OM
      • Muntner P
      • Rizk DV
      • et al.
      Dietary patterns and risk of death and progression to ESRD in individuals with CKD: a cohort study.
      Men tend to have a higher salt consumption,
      • ReF Agondi
      • MC Gallani
      • Rodrigues RC
      • Cornélio ME
      Relationship between beliefs regarding a low salt diet in chronic renal failure patients on dialysis.
      and be less compliant with sodium-restricted diets.
      • Crews DC
      • Kuczmarski MF
      • Miller ER
      • Zonderman AB
      • Evans MK
      • Powe NR.
      Dietary habits, poverty, and chronic kidney disease in an urban population.
      Conditions such as higher body mass index and increased plasma glucose levels were associated with the acceleration of CKD progression in men to a greater extent than in women.
      • Verhave JC
      • Hillege HL
      • Burgerhof JG
      • et al.
      Cardiovascular risk factors are differently associated with urinary albumin excretion in men and women.
      Hu et al
      • Hu EA
      • Coresh J
      • Anderson CAM
      • et al.
      Adherence to healthy dietary patterns and risk of CKD progression and all-cause mortality: findings from the CRIC (Chronic Renal Insufficiency Cohort) study.
      investigated the association of multiple dietary patterns with the risk of CKD progression (50% eGFR decline or kidney replacement therapy) and all-cause mortality in participants from CRIC. In three of four of the healthy dietary patterns evaluated, men scored worse than women (ie, men ate more unhealthily). Adherence to healthy dietary patterns was associated with a lower risk for CKD progression and all-cause death, independently of sex, but the study did not report analyses segregated by sex. Finally, studies also have suggested that men more often choose to start kidney replacement therapy, while women more often choose conservative care.
      • Morton RL
      • Turner RM
      • Howard K
      • Snelling P
      • Webster AC.
      Patients who plan for conservative care rather than dialysis: a national observational study in Australia.
      Research that elucidates why women progress more slowly than men in CKD may shed light on novel approaches to manage disease. However, efforts to tackle the rapid progression to dialysis of men also are warranted.

      FACT 2: MEN WITH CKD HAVE A HIGHER RISK OF DEATH THAN WOMEN

      Multiple studies coincide in that men with non–dialysis-dependent CKD have a higher mortality risk than women. The most recent study comes from the Stockholm CREAtinine Measurements project, which observed higher risk of both kidney replacement therapy and death for men, irrespective of their kidney function, CKD category, and previous eGFR slope.
      • Hodlmoser S
      • Carrero JJ
      • Kurnikowski A
      • et al.
      Kidney function, kidney replacement therapy, and mortality in men and women.
      In a nationwide study of Swedes referred to nephrology care and with CKD stages 3 to 5, men were 10% more likely to die than women of the same eGFR,
      • Swartling O
      • Rydell H
      • Stendahl M
      • Segelmark M
      • Trolle Lagerros Y
      • Evans M
      CKD progression and mortality among men and women: a nationwide study in Sweden.
      although this difference became less clear across more severe CKD stages. Similar observations were reported in CRIC, in addition showing higher risk of major cardiovascular events.
      • Toth-Manikowski SM
      • Yang W
      • Appel L
      • et al.
      Sex differences in cardiovascular outcomes in CKD: findings from the CRIC study.
      The CKD Outcomes and Practice Patterns Study
      • Hecking M
      • Tu C
      • Zee J
      • et al.
      Sex-specific differences in mortality and incident dialysis in the Chronic Kidney Disease Outcomes and Practice Patterns Study.
      observed that sequential adjustment for comorbidities minimally affected the higher risk of death and kidney replacement therapy of men, arguing that the differences may not be explained by biological factors, but perhaps attributed to social factors (ie, differences in the quality of care, access to care, and so forth). As a consequence of these findings, life expectancy is reduced in men (compared with women) in all eGFR categories except for CKD stage 5.
      • Turin TC
      • Tonelli M
      • Manns BJ
      • Ravani P
      • Ahmed SB
      • Hemmelgarn BR.
      Chronic kidney disease and life expectancy.
      Differences in outcomes between sexes tend to disappear upon the start of dialysis, an observation initially described by Villar et al
      • Villar E
      • Remontet L
      • Labeeuw M
      • Ecochard R.
      Effect of age, gender, and diabetes on excess death in end-stage renal failure.
      as the “cancellation of the survival advantage of women in dialysis.” Subsequent work from the European Renal Association register,
      • Carrero JJ
      • de Jager DJ
      • Verduijn M
      • et al.
      Cardiovascular and noncardiovascular mortality among men and women starting dialysis.
      ,
      • Vogelzang JL
      • van Stralen KJ
      • Noordzij M
      • et al.
      Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry.
      Dialysis Outcomes and Practice Patterns Study,
      • Hecking M
      • Bieber BA
      • Ethier J
      • 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).
      and others
      • Carrero JJ
      • de Mutsert R
      • Axelsson J
      • et al.
      Sex differences in the impact of diabetes on mortality in chronic dialysis patients.
      • Shah S
      • Leonard AC
      • Meganathan K
      • Christianson AL
      • Thakar CV.
      Temporal trends in incident mortality in dialysis patients: focus on sex and racial disparities.
      • Ros S
      • Remon C
      • Qureshi AR
      • Quiros P
      • Lindholm B
      • Carrero JJ.
      Increased risk of fatal infections in women starting peritoneal dialysis.
      showed that this absence of difference on death risks between sexes was attributed in part by higher noncardiovascular death risks among women (infections and cancer), but cardiovascular mortality remained higher in men.
      • Carrero JJ
      • de Jager DJ
      • Verduijn M
      • et al.
      Cardiovascular and noncardiovascular mortality among men and women starting dialysis.
      ,
      • Vogelzang JL
      • van Stralen KJ
      • Noordzij M
      • et al.
      Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry.
      These worse outcomes in men with CKD occur despite a better provision of care or a more aggressive treatment of risk factors. In a recent qualitative interview study,
      • Tong A
      • Evangelidis N
      • Kurnikowski A
      • et al.
      Nephrologists’ perspectives on gender disparities in CKD and dialysis.
      nephrologists voiced that they believed more attention was paid to men and their symptoms. Men are more likely to start dialysis at higher levels of kidney function than women and have lower rates of dialysis withdrawal.
      • Wright S
      • Klausner D
      • Baird B
      • et al.
      Timing of dialysis initiation and survival in ESRD.
      • 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.
      • Stel VS
      • Tomson C
      • Ansell D
      • et al.
      Level of renal function in patients starting dialysis: an ERA-EDTA Registry study.
      • Obrador GT
      • Arora P
      • Kausz AT
      • Ruthazer R
      • Pereira BJ
      • Levey AS.
      Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population.
      In the United Kingdom, men are referred to nephrologists earlier and at a higher eGFR that women,
      • John R
      • Webb M
      • Young A
      • Stevens PE.
      Unreferred chronic kidney disease: a longitudinal study.
      and men were more likely to receive a diagnostic code of CKD.
      • Kim LG
      • Cleary F
      • Wheeler DC
      • et al.
      How do primary care doctors in England and Wales code and manage people with chronic kidney disease? Results from the National Chronic Kidney Disease Audit.
      A Canadian cross-sectional study of people with CKD in primary care
      • Bello AK
      • Ronksley PE
      • Tangri N
      • et al.
      Quality of chronic kidney disease management in Canadian primary care.
      reported more frequent testing of urine albumin-creatinine ratio in men, compared with women. In Sweden, men with low eGFR were more likely to carry a diagnosis of CKD and be retested for albuminuria or creatinine than women.
      • Gasparini A
      • Evans M
      • Coresh J
      • et al.
      Prevalence and recognition of chronic kidney disease in Stockholm healthcare.
      In the United States, during the past 20 years, men have been more aware of their kidney disease than women.
      • Hodlmoser S
      • Winkelmayer WC
      • Zee J
      • et al.
      Sex differences in chronic kidney disease awareness among US adults, 1999 to 2018.
      These data come from the National Health and Nutrition Examination Survey in which participants responded to the question, “Have you ever been told by a health care professional you had weak or failing kidneys?” The response rates to this question may be interpreted, in part, as an indication that in health care more attention is attributed to CKD in men. In addition, in the United States, the likelihood of initiating renin-angiotensin inhibitors upon detection of incident albuminuria was higher in men.
      • Qiao Y
      • Shin JI
      • Chen TK
      • et al.
      Association of albuminuria levels with the prescription of renin-angiotensin system blockade.

      FACT 3: MEN WITH CKD MORE OFTEN SUFFER FROM CARDIOVASCULAR DISEASE THAN WOMEN

      Throughout all stages of CKD severity, men have a worse cardiovascular profile and more cardiovascular complications than women. In a recent study from Korea
      • Jung CY
      • Heo GY
      • Park JT
      • et al.
      Sex disparities and adverse cardiovascular and kidney outcomes in patients with chronic kidney disease: results from the KNOW-CKD.
      including patients with nondialysis CKD, men had higher coronary artery calcium measurements at baseline, a higher risk of accelerated coronary artery calcium progression over time, and a higher risk of cardiovascular events.
      • Jung CY
      • Heo GY
      • Park JT
      • et al.
      Sex disparities and adverse cardiovascular and kidney outcomes in patients with chronic kidney disease: results from the KNOW-CKD.
      The Korean National Health and Nutrition Examination Survey
      • Seong JM
      • Lee JH
      • Gi MY
      • et al.
      Gender difference in the association of chronic kidney disease with visceral adiposity index and lipid accumulation product index in Korean adults: Korean National Health and Nutrition Examination Survey.
      also showed that men with more severe CKD had progressively higher levels of visceral adiposity, but no such association was observed for women.
      • Seong JM
      • Lee JH
      • Gi MY
      • et al.
      Gender difference in the association of chronic kidney disease with visceral adiposity index and lipid accumulation product index in Korean adults: Korean National Health and Nutrition Examination Survey.
      In CRIC, men were more likely to be hospitalized for cardiovascular complications than women, although women had a higher rate of noncardiovascular complications than men.
      • Schrauben SJ
      • Chen HY
      • Lin E
      • et al.
      Hospitalizations among adults with chronic kidney disease in the United States: a cohort study.
      This excess cardiovascular disease (CVD) risk also is seen among patients on dialysis. In the analysis of baseline characteristics of the Dutch Netherlands Cooperative Study on the Adequacy of Dialysis trial, men who initiated dialysis had a higher cardiovascular disease prevalence (two-fold) and higher blood pressure than women, along with a higher body mass index and higher proportion of smokers.
      • Carrero JJ
      • de Mutsert R
      • Axelsson J
      • et al.
      Sex differences in the impact of diabetes on mortality in chronic dialysis patients.
      In another US trial,
      • Foley RN
      • Curtis BM
      • Randell EW
      • Parfrey PS.
      Left ventricular hypertrophy in new hemodialysis patients without symptomatic cardiac disease.
      enrolled men had a higher left ventricular mass index than women. In a cohort study from Germany, male patients undergoing hemodialysis had higher calcification scores and higher CVD event rates than women.
      • Schlieper G
      • Brandenburg V
      • Djuric Z
      • et al.
      Risk factors for cardiovascular calcifications in non-diabetic Caucasian haemodialysis patients.
      Those studies are more than a decade old, and we do not believe that they represent the risk profile of patients nowadays. In the EQUAL study, including 1,479 elderly patients with incident dialysis stage 4 from five European countries during 2012 to 2018, men continued to smoke and had hypertension or cardiovascular disease comorbidity more often than women.
      • van de Luijtgaarden MWM
      • Caskey FJ
      • Wanner C
      • et al.
      Uraemic symptom burden and clinical condition in women and men of >/=65 years of age with advanced chronic kidney disease: results from the EQUAL study.
      The excess CVD risk in men with CKD compared with women resembles the differences in the general population, which are attributed in part to the cardioprotective effect of estrogen in women and, as alluded earlier, a more unhealthy lifestyle in men. There are, however, several CKD-specific risk factors that operate differently in men and women.

      Hyperphosphatemia

      Hyperphosphatemia is lower in men with CKD, but associated more strongly with CVD outcomes than in women. Maintenance of phosphate levels in the normal range through dietary and pharmacologic strategies is recommended by all major nephrology guidelines, suggesting ranges of normality that do not make a distinction between sexes. Thus, we find it intriguing to say the least, that a wealth of community-based studies, as well as studies of patients with CKD, have reported serum phosphate levels being significantly lower, not higher, in men compared with women.
      • Tonelli M
      • Sacks F
      • Pfeffer M
      • Gao Z
      • Curhan G
      • Investigators CARET.
      Relation between serum phosphate level and cardiovascular event rate in people with coronary disease.
      • Onufrak SJ
      • Bellasi A
      • Cardarelli F
      • et al.
      Investigation of gender heterogeneity in the associations of serum phosphorus with incident coronary artery disease and all-cause mortality.
      • Martín M
      • Valls J
      • Betriu A
      • Fernández E
      • Valdivielso JM.
      Association of serum phosphorus with subclinical atherosclerosis in chronic kidney disease. Sex makes a difference.
      • Eddington H
      • Hoefield R
      • Sinha S
      • et al.
      Serum phosphate and mortality in patients with chronic kidney disease.
      • Bellasi A
      • Mandreoli M
      • Baldrati L
      • et al.
      Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction.
      The underlying reasons are not clear,
      • Cobo G
      • Hecking M
      • Port FK
      • et al.
      Sex and gender differences in chronic kidney disease: progression to end-stage renal disease and haemodialysis.
      but it is even more interesting that despite men having lower levels, hyperphosphatemia is associated with subclinical atherosclerosis, cardiovascular events, and death only in men.
      • Onufrak SJ
      • Bellasi A
      • Cardarelli F
      • et al.
      Investigation of gender heterogeneity in the associations of serum phosphorus with incident coronary artery disease and all-cause mortality.
      • Martín M
      • Valls J
      • Betriu A
      • Fernández E
      • Valdivielso JM.
      Association of serum phosphorus with subclinical atherosclerosis in chronic kidney disease. Sex makes a difference.
      • Eddington H
      • Hoefield R
      • Sinha S
      • et al.
      Serum phosphate and mortality in patients with chronic kidney disease.
      • Bellasi A
      • Mandreoli M
      • Baldrati L
      • et al.
      Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction.
      • Yoo KD
      • Kang S
      • Choi Y
      • et al.
      Sex, age, and the association of serum phosphorus with all-cause mortality in adults with normal kidney function.
      Each 1 mg/dL increase in serum phosphate level in men with stable CVD was associated with a 4.52 g/m2 increase in left ventricular mass, whereas no significant association between higher serum phosphorus level and left ventricular mass was noted in women.
      • Saab G
      • Whooley MA
      • Schiller NB
      • Ix JH.
      Association of serum phosphorus with left ventricular mass in men and women with stable cardiovascular disease: data from the Heart and Soul Study.
      Whether more stringent phosphate control would benefit men with CKD warrants further study.

      Uncontrolled Blood Pressure

      Uncontrolled blood pressure is more common in men with CKD and possibly a greater risk factor for CKD progression than in women. Hypertension is a well-known risk factor for developing CKD,
      • Garofalo C
      • Borrelli S
      • Pacilio M
      • et al.
      Hypertension and prehypertension and prediction of development of decreased estimated GFR in the general population: a meta-analysis of cohort studies.
      progressing to end-stage kidney disease,
      • Reynolds K
      • Gu D
      • Muntner P
      • et al.
      A population-based, prospective study of blood pressure and risk for end-stage renal disease in China.
      and suffering from cardiovascular disease,
      • Kearney PM
      • Whelton M
      • Reynolds K
      • Muntner P
      • Whelton PK
      • He J.
      Global burden of hypertension: analysis of worldwide data.
      or premature death.
      GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016.
      Hypertension is generally more common among men than among women.
      • Ramirez LA
      • Sullivan JC.
      Sex differences in hypertension: where we have been and where we are going.
      Weldegiorgis and Woodward
      • Weldegiorgis M
      • Woodward M.
      The impact of hypertension on chronic kidney disease and end-stage renal disease is greater in men than women: a systematic review and meta-analysis.
      conducted a systematic review and meta-analysis to evaluate whether women and men with hypertension are at a similar risk of developing CKD outcomes. Their analysis showed that the effect of hypertension on the composite end point of incident CKD or end-stage kidney disease (ESKD) was different between sexes. Specifically, the risk ratio of hypertension compared with ideal blood pressure was 1.56 (95% confidence interval [CI], 1.39-1.75) in women and 2.06 (95% CI, 1.64-2.60) in men.
      • Weldegiorgis M
      • Woodward M.
      The impact of hypertension on chronic kidney disease and end-stage renal disease is greater in men than women: a systematic review and meta-analysis.
      This result means that, compared with men, hypertension in women conferred a 23% lower kidney risk (relative risk, 0.77; 95% CI, 0.63-0.95) with no significant heterogeneity between studies (I2 = 17.7%). Two possible explanations are proposed to explain why hypertension conferred approximately a fifth lower excess risk of kidney disease in women, as follows: on the one hand, men may have poor adherence to antihypertensive medications, poor lifestyle choices, and more preexisting conditions that could put them at high risk of ESKD and death; on the other hand, access to timely and good-quality health care is an important modifiable factor that may cause a considerable disparity in the CKD risk profile between women and men. Limited access to medical care may result in a delayed CKD diagnosis, inadequate education in diet and self-care, insufficient access to medication or monitoring, and suboptimal treatment and follow-up evaluation. Presently, our knowledge about sex differences in the diagnosis and management of CKD is limited; not all patients may be receiving adequate guideline-recommended care, and conscious or unconscious biases could lead to fewer women having their CKD detected, monitored, and managed (discussed earlier). A cohort study of 906 patients with hypertension and CKD stages 2 to 5 attending nephrology consultation
      • Minutolo R
      • Gabbai FB
      • Agarwal R
      • et al.
      Sex difference in ambulatory blood pressure control associates with risk of ESKD and death in CKD patients receiving stable nephrology care.
      investigated the association between blood pressure control and the risks of kidney replacement therapy or death. Although office blood pressure was similar in men and women, daytime and nighttime ambulatory blood pressures were higher in men. In unadjusted models, the rates of kidney replacement therapy and mortality associated with off-target blood pressure were both numerically higher in men compared with women, but interaction terms did not attain statistical significance.

      FACT 4: MEN MAY REACT TO THEIR CKD WITH DENIAL

      The worse clinical outcomes for men with CKD discussed earlier contrast with the recurrent finding that they score their quality of life better than women.
      • Liu WJ
      • Chew TF
      • Chiu AS
      • Zaki M.
      Quality of life of dialysis patients in Malaysia.
      • Germin-Petrovic D
      • Mesaros-Devcic I
      • Lesac A
      • et al.
      Health-related quality of life in the patients on maintenance hemodialysis: the analysis of demographic and clinical factors.
      • Kutner NG
      • Zhang R
      • Brogan D.
      Race, gender, and incident dialysis patients' reported health status and quality of life.
      • Vazquez I
      • Valderrabano F
      • Fort I
      • et al.
      [Differences in health-related quality of life between male and female hemodialysis patients].
      • Lopes AA
      • Bragg-Gresham JL
      • Goodkin DA
      • et al.
      Factors associated with health-related quality of life among hemodialysis patients in the DOPPS.
      • Poulsen CG
      • Kjaergaard KD
      • Peters CD
      • Jespersen B
      • Jensen JD.
      Quality of life development during initial hemodialysis therapy and association with loss of residual renal function.
      • Wight JP
      • Edwards L
      • Brazier J
      • Walters S
      • Payne JN
      • Brown CB.
      The SF36 as an outcome measure of services for end stage renal failure.
      Men on dialysis report a lower symptom burden and less severe symptoms than women,
      • Lopes AA
      • Bragg-Gresham JL
      • Goodkin DA
      • et al.
      Factors associated with health-related quality of life among hemodialysis patients in the DOPPS.
      ,
      • Molarius A
      • Janson S.
      Self-rated health, chronic diseases, and symptoms among middle-aged and elderly men and women.
      • 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.
      • Weisbord SD
      • Fried LF
      • Arnold RM
      • et al.
      Prevalence, severity, and importance of physical and emotional symptoms in chronic hemodialysis patients.
      • Caplin B
      • Kumar S
      • Davenport A.
      Patients' perspective of haemodialysis-associated symptoms.
      • Lopes GB
      • Matos CM
      • Leite EB
      • et al.
      Depression as a potential explanation for gender differences in health-related quality of life among patients on maintenance hemodialysis.
      and also take less time to recover after a dialysis session than women.
      • Caplin B
      • Kumar S
      • Davenport A.
      Patients' perspective of haemodialysis-associated symptoms.
      A recent analysis from EQUAL evaluated uremic symptom burden,
      • van de Luijtgaarden MWM
      • Caskey FJ
      • Wanner C
      • et al.
      Uraemic symptom burden and clinical condition in women and men of >/=65 years of age with advanced chronic kidney disease: results from the EQUAL study.
      illustrating that men and women differ in their uremic symptoms, and/or may be more concerned over certain uremic symptoms more than others. Symptoms such as bone or joint pain, leg swelling, trouble staying asleep, and shortness of breath predominantly were reported by women, while men more often reported difficulty in becoming sexually aroused and a decreased interest in sex.
      Men and women may experience and react differently to ESKD and may choose to express it differently.
      • Kutner NG
      • Zhang R
      • Brogan D.
      Race, gender, and incident dialysis patients' reported health status and quality of life.
      Depression is diagnosed less often in men with CKD,
      • Hecking M
      • Bieber BA
      • Ethier J
      • 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).
      ,
      • van de Luijtgaarden MWM
      • Caskey FJ
      • Wanner C
      • et al.
      Uraemic symptom burden and clinical condition in women and men of >/=65 years of age with advanced chronic kidney disease: results from the EQUAL study.
      ,
      • Vazquez I
      • Valderrabano F
      • Fort I
      • et al.
      [Differences in health-related quality of life between male and female hemodialysis patients].
      ,
      • Weissman MM
      • Bland RC
      • Canino GJ
      • et al.
      Cross-national epidemiology of major depression and bipolar disorder.
      and it is not well acknowledged that in the general population, although twice as many women than men are diagnosed with depression, twice as many men than women commit suicide.
      • Hawton K
      • van Heeringen K.
      Suicide.
      Men more often adopt avoidance (eg, heavy drinking and smoking) as a coping strategy,
      • Yeh SC
      • Chou HC.
      Coping strategies and stressors in patients with hemodialysis.
      and they perceive themselves as better able to cope with the physical aspects of their disease.
      • Yeh SC
      • Chou HC.
      Coping strategies and stressors in patients with hemodialysis.
      • Yeh SCJ
      • Huang CH
      • Chou HC
      • Wan TTH.
      Gender differences in stress and coping among elderly patients on hemodialysis.
      • Tu HY
      • Shao JH
      • Wu FJ
      • Chen SH
      • Chuang YH.
      Stressors and coping strategies of 20-45-year-old hemodialysis patients.
      • Lindqvist R
      • Carlsson M
      • Sjoden PO.
      Coping strategies and quality of life among patients on hemodialysis and continuous ambulatory peritoneal dialysis.
      The meaning of these findings is not necessarily that men do not care about their health issues, but that they may find it difficult to express their fears in response to the social pressure/expectation of them being tough, strong, and responsible for the economy of the household.
      • Barsky AJ
      • Peekna HM
      • Borus JF.
      Somatic symptom reporting in women and men.
      As a consequence, men use health services less often than women, are less likely than women to engage in routine checks, and arrive to the hospital often too late.
      • Courtenay WH.
      Constructions of masculinity and their influence on men's well-being: a theory of gender and health.
      ,
      • Wang Y
      • Hunt K
      • Nazareth I
      • Freemantle N
      • Petersen I.
      Do men consult less than women? An analysis of routinely collected UK general practice data.
      Women are more likely to seek advice from peers, magazines, books, internet, and television than men. Men tend not to rely on the experience of their peers, preferring to try to live life as normal,
      • Banks I.
      No man's land: men, illness, and the NHS.
      showing “strength in silence,” which might affect their desire to being informed on how to best manage their disease.
      • Farrimond H.
      Beyond the caveman: rethinking masculinity in relation to men's help-seeking.

      SUMMARY AND CONCLUSIONS

      The idea that men and women compete in society has often been the subject of art (Fig. 1).
      Figure 1
      Figure 1Edgar Degas “Young Spartans Exercising,” also known as “Young Spartan Girls Challenging Boys” (∼1860). National Gallery, London, UK.
      However, if survival was the goal of human beings, then men would have to be considered as losing this battle. Notwithstanding the important gaps that may exist in the recognition and management of CKD among women, this review shows the other side of the coin, namely that men with CKD are at a consistently higher risk of worse clinical outcomes. Efforts to improve this and ensure equitable care between sexes could have important implications for justice and could reduce the burden of CKD.

      REFERENCES

        • Mauvais-Jarvis F
        • Bairey Merz N
        • Barnes PJ
        • et al.
        Sex and gender: modifiers of health, disease, and medicine.
        Lancet. 2020; 396: 565-582
        • Mauvais-Jarvis F
        • Berthold HK
        • Campesi I
        • et al.
        Sex- and gender-based pharmacological response to drugs.
        Pharmacol Rev. 2021; 73: 730-762
        • Carrero JJ
        • Hecking M
        • Chesnaye NC
        • Jager KJ.
        Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease.
        Nat Rev Nephrol. 2018; 14: 151-164
        • Carrero JJ
        • Hecking M
        • Ulasi I
        • Sola L
        • Thomas B.
        Chronic kidney disease, gender, and access to care: a global perspective.
        Semin Nephrol. 2017; 37: 296-308
        • Cobo G
        • Hecking M
        • Port FK
        • et al.
        Sex and gender differences in chronic kidney disease: progression to end-stage renal disease and haemodialysis.
        Clin Sci (Lond). 2016; 130: 1147-1163
        • Carrero JJ.
        Gender differences in chronic kidney disease: underpinnings and therapeutic implications.
        Kidney Blood Press Res. 2010; 33: 383-392
        • Canestaro WJ
        • Hendrix N
        • Bansal A
        • Sullivan SD
        • Devine EB
        • Carlson JJ.
        Favorable and publicly funded studies are more likely to be published: a systematic review and meta-analysis.
        J Clin Epidemiol. 2017; 92: 58-68
        • Grams ME
        • Chow EK
        • Segev DL
        • Coresh J.
        Lifetime incidence of CKD stages 3-5 in the United States.
        Am J Kidney Dis. 2013; 62: 245-252
        • Inker LA
        • Tighiouart H
        • Aspelund T
        • et al.
        Lifetime risk of stage 3-5 CKD in a community-based sample in Iceland.
        Clin J Am Soc Nephrol. 2015; 10: 1575-1584
        • Hecking M
        • Bieber BA
        • Ethier J
        • 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. 2014; 11e1001750
        • Antlanger M
        • Noordzij M
        • van de Luijtgaarden M
        • et al.
        Sex differences in kidney replacement therapy initiation and maintenance.
        Clin J Am Soc Nephrol. 2019; 14: 1616-1625
        • Kainz A
        • Berner C
        • Ristl R
        • et al.
        Sex-specific analysis of haemodialysis prevalence, practices and mortality over time: the Austrian Dialysis Registry from 1965 to 2014.
        Nephrol Dial Transplant. 2019; 34: 1026-1035
        • Carrero JJ
        • de Jager DJ
        • Verduijn M
        • et al.
        Cardiovascular and noncardiovascular mortality among men and women starting dialysis.
        Clin J Am Soc Nephrol. 2011; 6: 1722-1730
        • Neugarten J
        • Acharya A
        • Silbiger SR.
        Effect of gender on the progression of nondiabetic renal disease: a meta-analysis.
        J Am Soc Nephrol. 2000; 11: 319-329
        • Jafar TH
        • Schmid CH
        • Stark PC
        • 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. 2003; 18: 2047-2053
        • Neugarten J
        • Golestaneh L.
        Influence of sex on the progression of chronic kidney disease.
        Mayo Clin Proc. 2019; 94: 1339-1356
        • Minutolo R
        • Gabbai FB
        • Chiodini P
        • et al.
        Sex differences in the progression of CKD among older patients: pooled analysis of 4 cohort studies.
        Am J Kidney Dis. 2020; 75: 30-38
        • Swartling O
        • Rydell H
        • Stendahl M
        • Segelmark M
        • Trolle Lagerros Y
        • Evans M
        CKD progression and mortality among men and women: a nationwide study in Sweden.
        Am J Kidney Dis. 2021; 78 (e191): 190-199
        • Ricardo AC
        • Yang W
        • Sha D
        • et al.
        Sex-related disparities in CKD progression.
        J Am Soc Nephrol. 2019; 30: 137-146
        • Bonneric S
        • Karadkhele G
        • Couchoud C
        • Patzer RE
        • Greenbaum LA
        • Hogan J.
        Sex and glomerular filtration rate trajectories in children.
        Clin J Am Soc Nephrol. 2020; 15: 320-329
        • Elliot SJ
        • Berho M
        • Korach K
        • et al.
        Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis.
        Kidney Int. 2007; 72: 464-472
        • Metcalfe PD
        • Leslie JA
        • Campbell MT
        • Meldrum DR
        • Hile KL
        • Meldrum KK.
        Testosterone exacerbates obstructive renal injury by stimulating TNF-alpha production and increasing proapoptotic and profibrotic signaling.
        Am J Physiol Endocrinol Metab. 2008; 294: E435-E443
        • Reckelhoff JF
        • Zhang H
        • Srivastava K.
        Gender differences in development of hypertension in spontaneously hypertensive rats: role of the renin-angiotensin system.
        Hypertension. 2000; 35: 480-483
        • Carrero JJ.
        Testosterone deficiency at the crossroads of cardiometabolic complications in CKD.
        Am J Kidney Dis. 2014; 64: 322-325
        • Carrero JJ
        • Stenvinkel P.
        The vulnerable man: impact of testosterone deficiency on the uraemic phenotype.
        Nephrol Dial Transplant. 2012; 27: 4030-4041
        • Baylis C.
        Sexual dimorphism in the aging kidney: differences in the nitric oxide system.
        Nat Rev Nephrol. 2009; 5: 384-396
        • Matsuda T
        • Yamamoto T
        • Muraguchi A
        • Saatcioglu F.
        Cross-talk between transforming growth factor-beta and estrogen receptor signaling through Smad3.
        J Biol Chem. 2001; 276: 42908-42914
        • Moxley G
        • Stern AG
        • Carlson P
        • Estrada E
        • Han J
        • Benson LL.
        Premenopausal sexual dimorphism in lipopolysaccharide-stimulated production and secretion of tumor necrosis factor.
        J Rheumatol. 2004; 31: 686-694
        • Ji H
        • Zheng W
        • Menini S
        • et al.
        Female protection in progressive renal disease is associated with estradiol attenuation of superoxide production.
        Gend Med. 2007; 4: 56-71
        • 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. 2014; 29: 1186-1194
        • Nitsch D.
        Is there a difference in metabolic burden between men and women?.
        Nephrol Dial Transplant. 2014; 29: 1110-1112
        • Gutierrez OM
        • Muntner P
        • Rizk DV
        • et al.
        Dietary patterns and risk of death and progression to ESRD in individuals with CKD: a cohort study.
        Am J Kidney Dis. 2014; 64: 204-213
        • ReF Agondi
        • MC Gallani
        • Rodrigues RC
        • Cornélio ME
        Relationship between beliefs regarding a low salt diet in chronic renal failure patients on dialysis.
        J Ren Nutr. 2011; 21: 160-168
        • Crews DC
        • Kuczmarski MF
        • Miller ER
        • Zonderman AB
        • Evans MK
        • Powe NR.
        Dietary habits, poverty, and chronic kidney disease in an urban population.
        J Ren Nutr. 2015; 25: 103-110
        • Verhave JC
        • Hillege HL
        • Burgerhof JG
        • et al.
        Cardiovascular risk factors are differently associated with urinary albumin excretion in men and women.
        J Am Soc Nephrol. 2003; 14: 1330-1335
        • Hu EA
        • Coresh J
        • Anderson CAM
        • et al.
        Adherence to healthy dietary patterns and risk of CKD progression and all-cause mortality: findings from the CRIC (Chronic Renal Insufficiency Cohort) study.
        Am J Kidney Dis. 2021; 77: 235-244
        • Morton RL
        • Turner RM
        • Howard K
        • Snelling P
        • Webster AC.
        Patients who plan for conservative care rather than dialysis: a national observational study in Australia.
        Am J Kidney Dis. 2012; 59: 419-427
        • Hodlmoser S
        • Carrero JJ
        • Kurnikowski A
        • et al.
        Kidney function, kidney replacement therapy, and mortality in men and women.
        Kidney Int Rep. 2022; 7: 444-454
        • Toth-Manikowski SM
        • Yang W
        • Appel L
        • et al.
        Sex differences in cardiovascular outcomes in CKD: findings from the CRIC study.
        Am J Kidney Dis. 2021; 78 (e201): 200-209
        • Hecking M
        • Tu C
        • Zee J
        • et al.
        Sex-specific differences in mortality and incident dialysis in the Chronic Kidney Disease Outcomes and Practice Patterns Study.
        Kidney Int Rep. 2022; 7: 410-423
        • Turin TC
        • Tonelli M
        • Manns BJ
        • Ravani P
        • Ahmed SB
        • Hemmelgarn BR.
        Chronic kidney disease and life expectancy.
        Nephrol Dial Transplant. 2012; 27: 3182-3186
        • Villar E
        • Remontet L
        • Labeeuw M
        • Ecochard R.
        Effect of age, gender, and diabetes on excess death in end-stage renal failure.
        J Am Soc Nephrol. 2007; 18: 2125-2134
        • Vogelzang JL
        • van Stralen KJ
        • Noordzij M
        • et al.
        Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry.
        Nephrol Dial Transplant. 2015; 30: 1028-1037
        • Carrero JJ
        • de Mutsert R
        • Axelsson J
        • et al.
        Sex differences in the impact of diabetes on mortality in chronic dialysis patients.
        Nephrol Dial Transplant. 2011; 26: 270-276
        • Shah S
        • Leonard AC
        • Meganathan K
        • Christianson AL
        • Thakar CV.
        Temporal trends in incident mortality in dialysis patients: focus on sex and racial disparities.
        Am J Nephrol. 2019; 49: 241-253
        • Ros S
        • Remon C
        • Qureshi AR
        • Quiros P
        • Lindholm B
        • Carrero JJ.
        Increased risk of fatal infections in women starting peritoneal dialysis.
        Perit Dial Int. 2013; 33: 487-494
        • Tong A
        • Evangelidis N
        • Kurnikowski A
        • et al.
        Nephrologists’ perspectives on gender disparities in CKD and dialysis.
        Kidney Int Rep. 2021; 7: 424-435
        • Wright S
        • Klausner D
        • Baird B
        • et al.
        Timing of dialysis initiation and survival in ESRD.
        Clin J Am Soc Nephrol. 2010; 5: 1828-1835
        • 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.
        Nephrol Dial Transplant. 2016; 31: 46-56
        • Stel VS
        • Tomson C
        • Ansell D
        • et al.
        Level of renal function in patients starting dialysis: an ERA-EDTA Registry study.
        Nephrol Dial Transplant. 2010; 25: 3315-3325
        • Obrador GT
        • Arora P
        • Kausz AT
        • Ruthazer R
        • Pereira BJ
        • Levey AS.
        Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population.
        Kidney Int. 1999; 56: 2227-2235
        • John R
        • Webb M
        • Young A
        • Stevens PE.
        Unreferred chronic kidney disease: a longitudinal study.
        Am J Kidney Dis. 2004; 43: 825-835
        • Kim LG
        • Cleary F
        • Wheeler DC
        • et al.
        How do primary care doctors in England and Wales code and manage people with chronic kidney disease? Results from the National Chronic Kidney Disease Audit.
        Nephrol Dial Transplant. 2018; 33: 1373-1379
        • Bello AK
        • Ronksley PE
        • Tangri N
        • et al.
        Quality of chronic kidney disease management in Canadian primary care.
        JAMA Netw Open. 2019; 2e1910704
        • Gasparini A
        • Evans M
        • Coresh J
        • et al.
        Prevalence and recognition of chronic kidney disease in Stockholm healthcare.
        Nephrol Dial Transplant. 2016; 31: 2086-2094
        • Hodlmoser S
        • Winkelmayer WC
        • Zee J
        • et al.
        Sex differences in chronic kidney disease awareness among US adults, 1999 to 2018.
        PLoS One. 2020; 15e0243431
        • Qiao Y
        • Shin JI
        • Chen TK
        • et al.
        Association of albuminuria levels with the prescription of renin-angiotensin system blockade.
        Hypertension. 2020; 76: 1762-1768
        • Jung CY
        • Heo GY
        • Park JT
        • et al.
        Sex disparities and adverse cardiovascular and kidney outcomes in patients with chronic kidney disease: results from the KNOW-CKD.
        Clin Res Cardiol. 2021; 110: 1116-1127
        • Seong JM
        • Lee JH
        • Gi MY
        • et al.
        Gender difference in the association of chronic kidney disease with visceral adiposity index and lipid accumulation product index in Korean adults: Korean National Health and Nutrition Examination Survey.
        Int Urol Nephrol. 2021; 53: 1417-1425
        • Schrauben SJ
        • Chen HY
        • Lin E
        • et al.
        Hospitalizations among adults with chronic kidney disease in the United States: a cohort study.
        PLoS Med. 2020; 17e1003470
        • Foley RN
        • Curtis BM
        • Randell EW
        • Parfrey PS.
        Left ventricular hypertrophy in new hemodialysis patients without symptomatic cardiac disease.
        Clin J Am Soc Nephrol. 2010; 5: 805-813
        • Schlieper G
        • Brandenburg V
        • Djuric Z
        • et al.
        Risk factors for cardiovascular calcifications in non-diabetic Caucasian haemodialysis patients.
        Kidney Blood Press Res. 2009; 32: 161-168
        • van de Luijtgaarden MWM
        • Caskey FJ
        • Wanner C
        • et al.
        Uraemic symptom burden and clinical condition in women and men of >/=65 years of age with advanced chronic kidney disease: results from the EQUAL study.
        Nephrol Dial Transplant. 2019; 34: 1189-1196
        • Tonelli M
        • Sacks F
        • Pfeffer M
        • Gao Z
        • Curhan G
        • Investigators CARET.
        Relation between serum phosphate level and cardiovascular event rate in people with coronary disease.
        Circulation. 2005; 112: 2627-2633
        • Onufrak SJ
        • Bellasi A
        • Cardarelli F
        • et al.
        Investigation of gender heterogeneity in the associations of serum phosphorus with incident coronary artery disease and all-cause mortality.
        Am J Epidemiol. 2009; 169: 67-77
        • Martín M
        • Valls J
        • Betriu A
        • Fernández E
        • Valdivielso JM.
        Association of serum phosphorus with subclinical atherosclerosis in chronic kidney disease. Sex makes a difference.
        Atherosclerosis. 2015; 241: 264-270
        • Eddington H
        • Hoefield R
        • Sinha S
        • et al.
        Serum phosphate and mortality in patients with chronic kidney disease.
        Clin J Am Soc Nephrol. 2010; 5: 2251-2257
        • Bellasi A
        • Mandreoli M
        • Baldrati L
        • et al.
        Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction.
        Clin J Am Soc Nephrol. 2011; 6: 883-891
        • Yoo KD
        • Kang S
        • Choi Y
        • et al.
        Sex, age, and the association of serum phosphorus with all-cause mortality in adults with normal kidney function.
        Am J Kidney Dis. 2016; 67: 79-88
        • Saab G
        • Whooley MA
        • Schiller NB
        • Ix JH.
        Association of serum phosphorus with left ventricular mass in men and women with stable cardiovascular disease: data from the Heart and Soul Study.
        Am J Kidney Dis. 2010; 56: 496-505
        • Garofalo C
        • Borrelli S
        • Pacilio M
        • et al.
        Hypertension and prehypertension and prediction of development of decreased estimated GFR in the general population: a meta-analysis of cohort studies.
        Am J Kidney Dis. 2016; 67: 89-97
        • Reynolds K
        • Gu D
        • Muntner P
        • et al.
        A population-based, prospective study of blood pressure and risk for end-stage renal disease in China.
        J Am Soc Nephrol. 2007; 18: 1928-1935
        • Kearney PM
        • Whelton M
        • Reynolds K
        • Muntner P
        • Whelton PK
        • He J.
        Global burden of hypertension: analysis of worldwide data.
        Lancet. 2005; 365: 217-223
      1. GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016.
        Lancet. 2017; 390: 1151-1210
        • Ramirez LA
        • Sullivan JC.
        Sex differences in hypertension: where we have been and where we are going.
        Am J Hypertens. 2018; 31: 1247-1254
        • Weldegiorgis M
        • Woodward M.
        The impact of hypertension on chronic kidney disease and end-stage renal disease is greater in men than women: a systematic review and meta-analysis.
        BMC Nephrol. 2020; 21: 506
        • Minutolo R
        • Gabbai FB
        • Agarwal R
        • et al.
        Sex difference in ambulatory blood pressure control associates with risk of ESKD and death in CKD patients receiving stable nephrology care.
        Nephrol Dial Transplant. 2021; 36: 2000-2007
        • Liu WJ
        • Chew TF
        • Chiu AS
        • Zaki M.
        Quality of life of dialysis patients in Malaysia.
        Med J Malaysia. 2006; 61: 540-546
        • Germin-Petrovic D
        • Mesaros-Devcic I
        • Lesac A
        • et al.
        Health-related quality of life in the patients on maintenance hemodialysis: the analysis of demographic and clinical factors.
        Coll Antropol. 2011; 35: 687-693
        • Kutner NG
        • Zhang R
        • Brogan D.
        Race, gender, and incident dialysis patients' reported health status and quality of life.
        J Am Soc Nephrol. 2005; 16: 1440-1448
        • Vazquez I
        • Valderrabano F
        • Fort I
        • et al.
        [Differences in health-related quality of life between male and female hemodialysis patients].
        Nefrologia. 2004; 24: 167-178
        • Lopes AA
        • Bragg-Gresham JL
        • Goodkin DA
        • et al.
        Factors associated with health-related quality of life among hemodialysis patients in the DOPPS.
        Qual Life Res. 2007; 16: 545-557
        • Poulsen CG
        • Kjaergaard KD
        • Peters CD
        • Jespersen B
        • Jensen JD.
        Quality of life development during initial hemodialysis therapy and association with loss of residual renal function.
        Hemodial Int. 2017; 21: 409-421
        • Wight JP
        • Edwards L
        • Brazier J
        • Walters S
        • Payne JN
        • Brown CB.
        The SF36 as an outcome measure of services for end stage renal failure.
        Qual Saf Health Care. 1998; 7: 209-221
        • Molarius A
        • Janson S.
        Self-rated health, chronic diseases, and symptoms among middle-aged and elderly men and women.
        J Clin Epidemiol. 2002; 55: 364-370
        • 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.
        J Ren Care. 2016; 42: 73-82
        • Weisbord SD
        • Fried LF
        • Arnold RM
        • et al.
        Prevalence, severity, and importance of physical and emotional symptoms in chronic hemodialysis patients.
        J Am Soc Nephrol. 2005; 16: 2487-2494
        • Caplin B
        • Kumar S
        • Davenport A.
        Patients' perspective of haemodialysis-associated symptoms.
        Nephrol Dial Transplant. 2011; 26: 2656-2663
        • Lopes GB
        • Matos CM
        • Leite EB
        • et al.
        Depression as a potential explanation for gender differences in health-related quality of life among patients on maintenance hemodialysis.
        Nephron Clin Pract. 2010; 115: c35-c40
        • Weissman MM
        • Bland RC
        • Canino GJ
        • et al.
        Cross-national epidemiology of major depression and bipolar disorder.
        JAMA. 1996; 276: 293-299
        • Hawton K
        • van Heeringen K.
        Suicide.
        Lancet. 2009; 373: 1372-1381
        • Yeh SC
        • Chou HC.
        Coping strategies and stressors in patients with hemodialysis.
        Psychosom Med. 2007; 69: 182-190
        • Yeh SCJ
        • Huang CH
        • Chou HC
        • Wan TTH.
        Gender differences in stress and coping among elderly patients on hemodialysis.
        Sex Roles. 2009; 60: 44-56
        • Tu HY
        • Shao JH
        • Wu FJ
        • Chen SH
        • Chuang YH.
        Stressors and coping strategies of 20-45-year-old hemodialysis patients.
        Collegian. 2014; 21: 185-192
        • Lindqvist R
        • Carlsson M
        • Sjoden PO.
        Coping strategies and quality of life among patients on hemodialysis and continuous ambulatory peritoneal dialysis.
        Scand J Caring Sci. 1998; 12: 223-230
        • Barsky AJ
        • Peekna HM
        • Borus JF.
        Somatic symptom reporting in women and men.
        J Gen Intern Med. 2001; 16: 266-275
        • Courtenay WH.
        Constructions of masculinity and their influence on men's well-being: a theory of gender and health.
        Soc Sci Med. 2000; 50: 1385-1401
        • Wang Y
        • Hunt K
        • Nazareth I
        • Freemantle N
        • Petersen I.
        Do men consult less than women? An analysis of routinely collected UK general practice data.
        BMJ Open. 2013; 3e003320
        • Banks I.
        No man's land: men, illness, and the NHS.
        BMJ. 2001; 323: 1058-1060
        • Farrimond H.
        Beyond the caveman: rethinking masculinity in relation to men's help-seeking.
        Health (London). 2012; 16: 208-225