A comprehensive analysis of sex-specific differences in the characteristics, treatment, and outcomes of individuals with end-stage renal disease undergoing dialysis might reveal treatment inequalities and targets to improve sex-specific patient care. Here we describe hemodialysis prevalence and patient characteristics by sex, compare the adult male-to-female mortality rate with data from the general population, and evaluate sex interactions with mortality. We assessed the Human Mortality Database and 206,374 patients receiving hemodialysis from 12 countries (Australia, Belgium, Canada, France, Germany, Italy, Japan, New Zealand, Spain, Sweden, the UK, and the US) participating in the international, prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) between June 1996 and March 2012. Among 35,964 sampled DOPPS patients with full data collection, we studied patient characteristics (descriptively) and mortality (via Cox regression) by sex. In all age groups, more men than women were on hemodialysis (59% versus 41% overall), with large differences observed between countries. The average estimated glomerular filtration rate at hemodialysis initiation was higher in men than women. The male-to-female mortality rate ratio in the general population varied from 1.5 to 2.6 for age groups <75 y, but in hemodialysis patients was close to one. Compared to women, men were younger (mean = 61.9±standard deviation 14.6 versus 63.1±14.5 y), were less frequently obese, were more frequently married and recipients of a kidney transplant, more frequently had coronary artery disease, and were less frequently depressed. Interaction analyses showed that the mortality risk associated with several comorbidities and hemodialysis catheter use was lower for men (hazard ratio [HR] = 1.11) than women (HR = 1.33, interaction p<0.001). This study is limited by its inability to establish causality for the observed sex-specific differences and does not provide information about patients not treated with dialysis or dying prior to a planned start of dialysis. Women's survival advantage was markedly diminished in hemodialysis patients. The finding that fewer women than men were being treated with dialysis for end-stage renal disease merits detailed further study, as the large discrepancies in sex-specific hemodialysis prevalence by country and age group are likely explained by factors beyond biology. Modifiable variables, such as catheter use, showing significant sex interactions suggest interventional targeting. Please see later in the article for the Editors' Summary Throughout life, the kidneys filter waste products (from the normal breakdown of tissues and from food) and excess water from the blood to make urine. Chronic kidney disease—an increasingly common condition globally—gradually destroys the kidney's filtration units (the nephrons). As the nephrons stop working, the rate at which the blood is filtered (the glomerular filtration rate) decreases, and waste products build up in the blood, eventually leading to life-threatening end-stage kidney (renal) disease. Symptoms of chronic kidney disease, which rarely occur until the disease is advanced, include tiredness, swollen feet and ankles, and frequent urination, particularly at night. Chronic kidney disease cannot be cured, but its progression can be slowed by controlling diabetes and other conditions that contribute to its development. End-stage kidney disease is treated by regular hemodialysis (a process in which blood is cleaned by passing it through a filtration machine) or by kidney transplantation. Like many other long-term conditions, the prevalence (the proportion of the population that has a specific disease) of chronic kidney disease and of end-stage renal disease, and treatment outcomes for these conditions, may differ between men and women. Some of these sex-specific differences may arise because of sex-specific differences in normal biological functions. Other sex-specific differences may be related to sex-specific differences in patient care or in patient awareness of chronic kidney disease. A comprehensive analysis of sex-specific differences among individuals with end-stage renal disease might identify both treatment inequalities and ways to improve sex-specific care. Here, in the Dialysis Outcomes and Practice Patterns Study (DOPPS), the researchers investigate sex-specific differences in the prevalence and practices of hemodialysis and in the characteristics of patients undergoing hemodialysis, and investigate the adult male-to-female mortality (death) rate among patients undergoing hemodialysis. The DOPPS is a prospective cohort study that is investigating the characteristics, treatment, and outcomes of adult patients undergoing hemodialysis in representative facilities in 19 countries (12 countries were available for analysis at the time of the current study). To investigate sex-specific differences in hemodialysis prevalence, the researchers compared data from the Human Mortality Database, which provides detailed population and mortality data for 37 countries, with data collected by the DOPPS. Forty-one percent of DOPPS patients were women, compared to 52% of the general population in 12 of the DOPPS countries. Next, the researchers used data collected from a randomly selected subgroup of patients to examine sex-specific differences in patient characteristics and mortality. The average estimated glomerular filtration rate at hemodialysis initiation was higher in men than women. Moreover, men were more frequently recipients of a kidney transplant than women. Notably, although in the general population in a given age group women were less likely to die than men, among hemodialysis patients, women were as likely to die as men. Finally, the researchers investigated which patient characteristics were associated with the largest sex-specific differences in mortality risk. The use of a hemodialysis catheter (a tube that is inserted into a patient's vein to transfer their blood into the hemodialysis machine) was associated with a lower mortality risk in men than in women. These findings show that, among patients treated with hemodialysis for end-stage renal disease, women differ from men in many ways. Although some of these sex-specific differences may be related to biology, others may be related to patient care and to patient awareness of chronic kidney disease. Because this is an observational study, these findings cannot prove that the reported differences in hemodialysis prevalence, treatment, and mortality are actually caused by being a man or a woman. Importantly, however, these findings suggest that hemodialysis may abolish the survival advantage that women have over men in the general population and that fewer women than men are being treated for end-stage-renal disease, even though chronic kidney disease is more common in women than in men. Finally, the finding that the use of hemodialysis catheters for access to veins is associated with a higher mortality risk among women than among men suggests that, where possible, women should be offered a surgical process called arteriovenous fistula placement, which is recommended for access to veins during long-term hemodialysis but which may, in the past, have been underused in women. Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001750.

Summary: Background and objectives: Recommendations to decrease the dialysate sodium (DNa) prescription demand analyses of patient outcomes. We analyzed morbidity and mortality at various levels of DNa, simultaneously accounting for interdialytic weight gain (IDWG) and for the mortality risk associated with lower predialysis serum sodium (SNa) levels. Design, setting, participants, & measurements: We used multiply-adjusted linear mixed models to evaluate the magnitude of IDWG and Cox proportional hazards models to assess hospitalizations and deaths in 29,593 patients from the Dialysis Outcomes and Practice Patterns Study with baseline DNa and SNa as predictors, categorized according to lowest to highest levels. Results: IDWG increased with higher DNa across all SNa categories, by 0.17% of body weight per 2 mEq/L higher DNa; however, higher DNa was not associated with higher mortality in a fully adjusted model (also adjusted for SNa; hazard ratio [HR]=0.98 per 2 mEq/L higher DNa, 95% confidence interval [CI] 0.95–1.02). Instead, higher DNa was associated with lower hospitalization risk (HR=0.97 per 2 mEq/L higher DNa, 95% CI 0.95–1.00, P=0.04). Additional adjustments for IDWG did not change these results. In sensitivity analyses restricted to study facilities, in which 90%–100% of patients have the same DNa (56%), the adjusted HR for mortality was 0.88 per 2 mEq/L higher DNa (95% CI 0.83–0.94). These analyses represented a pseudo-randomized experiment in which the association between DNa and mortality is unlikely to have been confounded by indication. Conclusions: In the absence of randomized prospective studies, the benefit of reducing IDWG by decreasing DNa prescriptions should be carefully weighed against an increased risk for adverse outcomes.

Predialysis volume overload is the sum of interdialytic weight gain (IDWG) and residual postdialysis volume overload. It results mostly from failure to achieve an adequate volume status at the end of the dialysis session. Recent developments in bioimpedance spectroscopy and possibly relative plasma volume monitoring permit noninvasive volume status assessment in hemodialysis patients. A large proportion of patients have previously been shown to be chronically volume overloaded predialysis (defined as >15% above ‘normal' extracellular fluid volume, equivalent to >2.5 liters on average), and to exhibit a more than twofold increased mortality risk. By contrast, the magnitude of the mortality risk associated with IDWG is much smaller and only evident with very large weight gains. Here we review the available evidence on volume overload and IDWG, and question the use of IDWG as an indicator of ‘nonadherence' by describing its association with postdialysis volume depletion. We also demonstrate the relationship between IDWG, volume overload and predialysis serum sodium concentration, and comment on salt intake. Discriminating between volume overload and IDWG will likely lead to a more appropriate management of fluid withdrawal during dialysis. Consensually, the present authors agree that this discrimination should be among the primary goals for dialysis caretakers today. In consequence, we recommend objective measures of volume status beyond mere evaluations of IDWG.