Sex-Specific Differences in Hemodialysis Prevalence and Practices and the Male-to-Female Mortality Rate: The Dialysis Outcomes and Practice Patterns Study (DOPPS) Manfred Hecking 1 , Brian A. Bieber 2 , Jean Ethier 3 , Alexandra Kautzky-Willer 4 , Gere Sunder-Plassmann 1 , Marcus D. Sa ¨ emann 1 , Sylvia P. B. Ramirez 2¤ , Brenda W. Gillespie 5 , Ronald L. Pisoni 2 , Bruce M. Robinson 2 , Friedrich K. Port 2 * 1 Clinical Division of Nephrology & Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, 2 Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States of America, 3 Centre Hospitalier de l’Universite ´ de Montre ´al, Montreal, Quebec, Canada, 4 Gender Medicine Unit, Clinical Division of Endocrinology & Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, 5 Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America 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 = 61.96standard deviation 14.6 versus 63.1614.5 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. Citation: Hecking M, Bieber BA, Ethier J, Kautzky-Willer A, Sunder-Plassmann G, et al. (2014) 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(10): e1001750. doi:10.1371/journal.pmed.1001750 Academic Editor: Maarten W. Taal, Royal Derby Hospital, United Kingdom Received December 6, 2013; Accepted September 18, 2014; Published October 28, 2014 Copyright: ß 2014 Hecking et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The DOPPS Program is supported by Amgen, Kyowa Hakko Kirin, AbbVie Inc., Sanofi Renal, Baxter Healthcare, and Vifor Fresenius Medical Care Renal Pharma, Ltd. Additional support for specific projects and countries is also provided in Canada by Amgen, BHC Medical, Janssen, Takeda, Kidney Foundation of Canada (for logistics support); in Germany by Hexal, DGfN, Shire, WiNe Institute; and for PDOPPS in Japan by the Japanese Society for Peritoneal Dialysis (JSPD). All support is provided without restrictions on publications. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The corresponding author has had full access to all the data in the study and takes final responsibility for the decision to submit for publication and the integrity of the data and accuracy of the manuscript. Competing Interests: BMR has received a speaker’s fee from Kyowa Hakko Kirin. RLP has received speaker’s fees from Amgen, Kyowa Hakko Kirin, and Vifor and has served on an advisory panel for Merck. The other authors have declared that no competing interests exist. Abbreviations: DOPPS, Dialysis Outcomes and Practice Patterns Study; eGFR, estimated glomerular filtration rate; HR, hazard ratio; MDRD, Modification of Diet in Renal Disease Study; NHANES, National Health and Nutrition Examination Survey. * Email: friedrich.port@arborresearch.org ¤ Current address: Abilitas Consulting, Singapore PLOS Medicine | www.plosmedicine.org 1 October 2014 | Volume 11 | Issue 10 | e1001750