Sex-specific differences in hemodialysis prevalence and practices and the male-to-female mortality rate: the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Abstract

Background: 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.

Methods and findings: 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.

Conclusions: 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.

Figure 1. Percent of population that are women, by age group, in the hemodialysis and general populations.

DOPPS data are prevalent hemodialysis patients from the DOPPS census (1996–2012). General population (GP) data are from the Human Mortality Database between 2000 and 2009.

Figure 2. Adult male-to-female mortality rate ratio, by age group, in the hemodialysis and general populations.

Mortality rate ratios are unadjusted. DOPPS data are prevalent hemodialysis patients from the DOPPS census (1996–2012). General population (GP) data are from the Human Mortality Database between 2000 and 2009.

Figure 3. Adjusted hazard ratios for the adult male-to-female mortality risk in hemodialysis patients, by region.

^aStratified by country (including US black race and US non-black race) and phase; n = 36,216 patients (n = 8,258 deaths) among patients with time on dialysis >90 d dialyzing 3× weekly. ^bCoronary artery disease, cerebrovascular disease, congestive heart failure, hypertension, peripheral vascular disease, other cardiovascular disease. ^cCancer, gastrointestinal bleed, lung disease, neurologic disorder, psychologic disorder, recurrent cellulitis. ^dEuropean countries = Belgium, France, Germany, Italy, Spain, Sweden, UK. ^eEducation, employment, marital status, smoking status, predialysis systolic blood pressure, blood flow rate, serum potassium, medication prescriptions (erythopoiesis-stimulating agent, phosphate binder, vitamin D, antihypertensive, antibiotic), prior parathyroidectomy, and prior transplant. A/NZ, Australia/New Zealand; BMI, body mass index; CV, cardiovascular; HD, hemodialysis; IDWG, interdialytic weight gain; N. America, North America; PTH, parathyroid hormone.

Figure 4. Analysis of sex interaction in the associations between hemodialysis patient characteristics and mortality.

p-Value is for interaction with sex, shown for variables with p<0.15 (n = 37 interactions tested). Adjusted for all variables listed in Tables 2 and 3, in addition to variables listed in Figure 3. BMI, body mass index; CI, confidence interval; CVD, cardiovascular disease; HD, hemodialysis; M, men; W, women.