Female patients with end-stage renal failure treated by hemodialysis had a low mortality rate and small patient number compared to male patients: 5-year follow-up study in Japan

Female patients with end-stage renal failure treated by hemodialysis had a low mortality rate and small patient number compared to male patients: 5-year follow-up study in Japan | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Female patients with end-stage renal failure treated by hemodialysis had a low mortality rate and small patient number compared to male patients: 5-year follow-up study in Japan Kuniyasu Takagi, Takuya Kishi, Taku Goto, Kohei Yamanouchi, Kazuhiko Yoshikawa, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4022656/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: This study aimed to evaluate gender differences in patient characteristics in maintenance hemodialysis in Takagi Hospital and, in particular, to evaluate gender differences in adverse events, gastrointestinal bleeding, and bone fractures during longitudinal follow-up period. Methods: This study included 151 patients undergoing maintenance hemodialysis for end-stage renal failure at Takagi Hospital, a regional core hospital in Japan, in December 2017. All the patients were followed up for five years or until mortality with monitoring in outpatient care. All patients were divided into a female group of 61 and a male group of 90. Patient characteristics and events were evaluated in the electronic medical record including gastrointestinal bleeding and bone fractures diagnosed and treated in Takagi Hospital. Gastrointestinal bleeding was diagnosed by endoscopy. Upper bone fractures included humeral fractures and radius fractures, and lower bone fractures were femoral neck fractures and vertebral compression fractures. Results: The patient number was small in females, which was due to the origin of renal failure with less frequency of diabetes mellitus ( P < 0.02). Mortality rate was significantly less in females ( P < 0.03) of younger generations less than 75 years old ( P < 0.014). Multivariate analysis indicated a decrease in diabetes mellitus (odd ratio: 2.3, 95% confidence interval: 1.1-4.8, P = 0.03) and less mortality in those younger than 75 years old (odd ratio: 0.2, 95% confidence interval: 0.1-0.8, P = 0.02) were independent characterized factors in females. Regarding adverse severe events during five years, gastrointestinal bleeding and mortality due to bleeding were not different between females and males. Bone fractures were high in females (females: 34.4% vs. males: 18.9%; P < 0.03), whereas the mortality rate of bone fractured patients was markedly high in males (females: 28.6% vs males: 76.5%; P = 0.003). The increase in mortality rate in males was in patients with lower body bone fractures ( P = 0.006). Conclusions: Diabetes mellitus-induced end-stage renal failure was less common in females. The mortality rate during hemodialysis was lower in females, especially in patients less than 75 years old. Lower body bone fractures exacerbated mortality more frequently in males compared to females. bone fracture gastrointestinal bleeding cardiovascular disease cerebrovascular disease infection diabetes mellitus aging fragility Background End-stage renal failure is a critical condition that necessitates proper medical intervention. Maintenance hemodialysis is commonly utilized in patients with end-stage renal failure to ensure survival (1-3). In Japan, hemodialysis is commonly administered to patients with end-stage renal failure, regardless of comorbidities, underlying diseases causing renal failure, and age (1-3), and is covered by the universal insurance system (4,5). According to the Renal Data Registry of the Japanese Society for Dialysis Therapy, the prevalence of hemodialysis patients in Japan has shown a time-dependent increase, reaching 15 patients per 10,000 population. Additionally, it is estimated that the number of female hemodialysispatients is approximately half that of male patients (3). Patients undergoing hemodialysis commonly present with various underlying diseases and comorbidities, such as diabetes mellitus (3,6), cardiovascular and cerebrovascular diseases (2,7,8), and malignant diseases (3). Moreover, the therapeutic management of chronic hemodialysis is associated with various adverse events, including gastrointestinal bleeding (9-12), bone fractures (13,14), infection (3,15), and cardiovascular and cerebrovascular diseases (2,7,8). The occurrence of adverse events may vary between females and males, and there is limited research focusing on gender differences in this area. This observational study sought to investigate gender disparities in the real-world patient characteristics of individuals undergoing maintenance hemodialysis at Takagi Hospital, a regional core hospital in Japan. Significantly, this study examined gender disparities in adverse events, gastrointestinal bleeding, and bone fractures over a five-year follow-up period. Methods Patients This longitudinal study included 151 patients in December 2017 undergoing maintenance hemodialysis for end-stage renal failure at the Human Dialysis Center of Nephrology in Takagi Hospital, a regional core hospital in Japan (12, 16,17). All patients who received maintenance hemodialysis for end-stage renal failure at Takagi Hospital were included, and the number of patients on December 1, 2017, was 151, who were followed up for five years or until mortality (12,14). Monitoring of patients in outpatient care with blood sampling was performed every month. Data source All patients were divided into two groups: a female, 61, and a male group, 90. Patient characteristics and events, including mortality and various clinical indicators, were detected in the electronic medical record for five years until December 2022. Age, duration of hemodialysis in December 2017, the origin of renal failure, and mortality were evaluated. A patient's blood test in December 2017 was detected, including hemoglobin, total protein, albumin, parathyroid hormone, iron, potassium, sodium, and calcium. Serious complications During the five-year observation period, complications of gastrointestinal bleeding and bone fractures were detected. Gastrointestinal bleeding was determined by gastrointestinal endoscopy. All patients with signs of gastrointestinal bleeding, including melena, hematemesis, and reduction of serum hemoglobin, underwent gastrointestinal endoscopy at Takagi Hospital. Of 151 patients, 32 (21.2%: 4.2% per year) were endoscopically diagnosed with gastrointestinal bleeding. All hemodialysis patients with gastrointestinal bleeding were treated in the emergency and gastroenterology departments of Takagi Hospital. Bone fractures were diagnosed in orthopedic surgery at Takagi Hospital. Upper bone fractures included humeral fractures, radius fractures, and others. The lower bone fractures were femoral neck fractures, femoral inter- and sub-trochanteric fractures, and vertebral compression fractures. All hemodialysis patients with bone fractures were treated at the orthopedic surgery of Takagi Hospital. Ethical approval This study was conducted by the Declaration of Helsinki with ethical review and approval from the Takagi Hospital's Kouhou-kai Ethical Committee (#495) and the International University of Health and Welfare Ethical Committee (21-Ifh-027). Written informed consent was obtained from all patients with hemodialysis. Statistical analysis Baseline characteristics of female and male patients were compared using the Chi-squared test for categorical variables and the Student- t test for continuous variables. We applied the multiple logistic regression model with explanatory variables with significance levels (univariate P value < 0.05 on statistical tests) except for closely gender-related factors of height and body weight. Odds ratios and 95% confidence interval were shown in the tables. JMP Pro 16 (SAS Institute Inc., Cary, NC, USA) was used for all analyses, and statistical significance was defined as P < 0.05. Results Characteristics of female patients compared with male patients. Patient characteristics between female and male patients who received hemodialysis for end-stage renal failure were compared, as indicated in Table 1. The number of patients was small in females compared to males, and this difference was due to the origin of renal failure. Namely, patients of diabetes mellitus-induced renal failure were significantly less in females compared to males ( P < 0.02). The mortality rate was significantly lower in female patients compared to male patients ( P < 0.03), and low mortality in females was mainly due to the younger generation less than 75 years old ( P < 0.014), and the mortality rate in patients older than 75 years old was equivalent in females and males. Blood test at entry on December 2017. Table 2 shows the blood test results when the patients entered the study in December 2017. Blood samples, including hemoglobin, total protein, albumin, parathyroid hormone, iron, potassium, sodium, and calcium, were not different between females and males. Multivariate analysis of characterized factors of female patients with hemodialysis As indicated in Table 3, multivariate analysis indicated that decreased number of diabetes mellitus patients for the origin of renal failure (odd ratio: 2.3, 95% confidence interval: 1.1-4.8, P = 0.03) and less mortality in younger than 75 years old (odd ratio: 0.2, 95% confidence interval: 0.1-0.8, P = 0.02) were independent characterized factors in female hemodialysis patients. Gastrointestinal bleeding and bone fractures during hemodialysis Table 4 shows the incidence of complications of gastrointestinal bleeding and bone fractures during a five-year follow-up period compared between female and male patients. Regarding upper gastrointestinal bleeding, incidence and mortality due to bleeding were not different between females and males. The incidence of lower gastrointestinal bleeding was less than that of upper gastrointestinal bleeding, and incidence and mortality were not different between females and males. The complication rate of bone fracture was high in females compared to males (females: 34.4% vs. males: 18.9%; P < 0.03), whereas the mortality rate of bone fractured patients was markedly high in males compared to females (females: 28.6% vs. males: 76.5%; P = 0.003). The increase in mortality rate in males was definitely in patients with lower body bone fractures ( P = 0.006). Discussion The current five-year follow-up study conducted at a regional core hospital in Japan has revealed the clinical characteristics of female patients undergoing chronic hemodialysis for end-stage renal failure, in comparison to male patients. Specifically, i) The incidence of end stage renal failure attributed to diabetes mellitus was lower in females than in males. ii) Mortality rates during hemodialysis were lower in females, particularly among patients younger than 75 years old. iii) The incidence of upper and lower major gastrointestinal bleeding was similar between females and males. iv) While bone fractures were more common in female patients undergoing hemodialysis, mortality was higher in male patients with lower bone fractures during hemodialysis. Lower prevalence of chronic hemodialysis was observed in females compared males in the study, which can be attributed due the a incidence number of end-stage renal caused by diabetes mellitus in females. Nevertheless, the incidence of hemodialysis in patients with nephrogenic diseases was similar in both genders. This finding was corroborated by the 2022 annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (3). In 2016, the number of diabetes mellitus patients in Japan was approximately 10 million, with female patients accounting for half of the male patients due to lifestyle-related diseases (18). This gender discrepancy may be a contributing factor tothe lower number of female patients undergoing chronic hemodialysis. The mortality among individuals under than 75 of age old, was higher in male than in female, while the mortality among those aged 75 and the old was similar between in genders. In numerous studies, cardiovascular and cerebrovascular diseases, as well as infectious diseases, have been identified as the primary comorbidities associated with mortality in hemodialysis patients (2, 3, 7, 8, 19-21). Additionally, it has been observed that vascular diseases are more prevalent among male patients in Japan (22). The current study did not precisely assess the specific causes of mortality for each patient, indicating a need for futher invstigation. As demonstrated in the current study, bone fractures resulted in higher mortality rates among male patients compared to female patients, potentially contributing to gender disparities in mortality among hemodialysis patients. Lower body bone fractures including vertebral compression and femoral fractures, along with concomitant fragility elderly populations, generations, emerged as significant societal concerns problems in Japan and nations countries (23-25). As previously shown (26), bone fractures pose a complex issue for hemodialysis patients and were found to be frequent in the current study, occurring at a rate of 27.2% over 5 years (5.4% per year). The incidence of complications from bone fractures was found to be higher in female hemodialysis patients compared to male patients, with rates of 34.4% and 18.9% respectively. The mortality rate among hemodialysis patients with complicated lower body bone fractures was notably higher in male patients (30.8% for females vs. 84.6% for males). The findings indicate that lower body bone fractures may lead to significant harm, such as fragility, in hemodialysis patients, with a lesser impact observed in females compared to males. The current retrospective follow-up study has several limitations. The sample size was limited in the single-institution study conducted at the regional core hospital in Japan. The therapeutic approach and the number of end-stage renal failure patients may vary from one country to another. The duration of hemodialysis treatment for the patient, spanning five years, was deemed insufficient. It is important to emphasize that all 151 patients were closely monitored at Takagi Hospital and received comprehensive medical attention. Conclusions End-stage renal failure induced by diabetes mellitus was prevalent frequent in females than in males, whereas disease-induced renal failure induced by nephrogenic disease equally distributed between in females and males. Mortality rates were lower among female hemodialysis patients, particularly those under 75 years of age and those with lower body bone fracture complications. Declarations Acknowledgements We would like to appreciate Professor Tsutomu Yamazaki, the International University of Health and Welfare Graduate School of Medicine, for invaluable advice and direction. Contributor roles Methodology and writing original draft: Kuniyasu Takagi. Methodology and supervision: Takuya Kishi and Tomohiro Imamura. Methodology: Taku Goto, Shiki Nakayama, Kohei Yamanouchi, Kazuhiko Yoshikawa, Yuichiro Akiyoshi, and Koji Onozawa. Formal analysis: Ayako Takamori. Supervision: Kazuma Fujimoto. Ethics approval and consent to participate Ethical review and approval from the Takagi Hospital's Kouhou-kai Ethical Committee (#495) and the International University of Health and Welfare Ethical Committee (21-Ifh-027). Written informed consent was obtained from all patients with hemodialysis. Consent for publication Not applicable. Funding This research received no external funding. Avaliability of data and materials The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Disclosure statement The authors declare no conflicts of interest regarding this study. References Kobayashi S, Ohtake T. The characteristics of dialysis membranes: benefits of the AN69 membrane in hemodialysis patients. J Clin Med. 2023;12:1123. Zoccali C, Mallamaci F, Adamczak M, de Oliveira RB, Massy ZA, Sarafidis P, et al. Cardiovascular complications in chronic kidney disease - a review from the European Renal and Cardiovascular Medicine Working Group of the European Renal Association. Cardiovasc Res. 2023;119:2017-2032. Hanafusa N, Abe M, Joki N, Hoshino J, Taniguchi M, Kikuchi K, et al. 2022 annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry. J Jpn Soc Dial Ther. 2023;56:473-536 (in Japanese, English abstract). Fujimoto S, Tsuruoka N, Esaki M, Takamori A, Sakata Y, Shimoda R, et al. Decline incidence in upper gastrointestinal bleeding in several recent years: data of the Japan claims database of 13 million accumulated patients. J Clin Biochem Nutr. 2021;68:95-100. Takagi K, Matugaki R, Fujimoto K, Mine Y, Muramatsu K, Fujino Y, et al. Analysis of the risk factors of mortality in elderly patients with hip fracture using a combined database of medical and long-term care insurance claims data. J Orthop Sci. 2023;28:627-630. Mark PB, Sarafidis P, Ekart R, Ferro CJ, Balafa O, Fernandez-Fernandez B, et al. SGLT2i for evidence-based cardiorenal protection in diabetic and non-diabetic chronic kidney disease: a comprehensive review by EURECA-m and ERBP working groups of ERA. Nephrol Dial Transplant. 2023;38:2444-2455. Tobe A, Sawano M, Kohsaka S, Ishii H, Tanaka A, Numasawa Y, et al. Ischemic and bleeding outcomes in patients who underwent percutaneous coronary intervention with chronic kidney disease or dialysis (from a Japanese Nationwide Registry). Am J Cardiol. 2023;195:37-44. Kishi T, Kitajima A, Yamanouchi K, Hirooka Y, Toda S, Takamori A, et al. Low body mass index without malnutrition is an independent risk factor for major cardiovascular events in patients with hemodialysis. Int Heart J. 2022;63:948-952. Tsai TJ, Chen WC, Huang YT, Yang YH, Feng IC, Wu WC, et al. Hemodialysis increases the risk of lower gastrointestinal bleeding and angiodysplasia bleeding: a nationwide population study. Gastroenterol Res Pract. 2020;2020: 7206171. Niikura R, Aoki T, Kojima T, Kawahara T, Tamada A, Nakamura H, et al. Natural history of upper and lower gastrointestinal bleeding in hemodialysis patients: a dual-center long-term cohort study. J Gastroenterol Hepatol. 2021;36:112-117. Kitajima A, Kishi T, Yamanouchi K, Hirooka Y, Toda S, Takamori A, et al. Retrospective analysis of risk factors for mortality during hemodialysis at the general hospital that can treat comprehensive diseases. Intern Med. 2023; 62: 1117-1121. Nakayama S, Yamanouchi K, Takamori A, Goto T, Shimada F, Imamura T, et al. Gastrointestinal bleeding among 151 patients undergoing maintenance hemodialysis for end-stage renal failure: a 5-year follow-up study. Medicine (Baltimore) 2024; 103: e37274. Ginsberg C, Ix JH. Diagnosis and management of osteoporosis in advanced kidney disease: a review. Am J Kidney Dis. 2022;79:427-436. Yoshikawa A, Kishi T, Takamori A, Kitajima A, Goto T, Nakayama S, et al. Bone fractures in the lower body have high mortality rates with hemodialysis. Ther Apher, in press Kanamori H, Weber DJ, Flythe JE, Rutala WA. Waterborne outbreaks in hemodialysis patients and infection prevention. Open Forum Infect Dis. 2022;9:ofac058. Kawaura F, Kishi T, Yamamoto T, Nakayama S, Goto T, Tsurusawa R, et al. Age distribution and disease severity of COVID-19 patients continued to change in a time-dependent manner from May 2021 to April 2022 in the regional core hospital in Japan. Drug Discov Ther. 2023;17:60-65. Matsuo R, Imamura T, Takamori A, Kishi T, Minami M, Miyakawa J, et al. Improvement trend for individual health guidance intervention according to Japan clinical guidelines by public health nurses for type 2 diabetes mellitus individuals who visited for medical checkups regularly regardless pharmacotherapy: a case-control preliminary report. J Clin Biochem. Nutr. 2024;74:141-145. Report of Japan Prevention Association of Lifestyle Related Disease (in Japanese) http://seikatusshukanbyo.com/statistics/disease/diabetes/ Accessed January 24, 2024 Adenwalla SF, O'Halloran P, Faull C, Murtagh FEM, Graham-Brown MPM. Advance care planning for patients with end-stage kidney disease on dialysis: narrative review of the current evidence, and future considerations. J Nephrol. 2024 January 18. doi: 10.1007/s40620-023-01841-3. Ponce D, Nitsch D, Ikizler TA. Strategies to Prevent Infections in Dialysis Patients. Semin Nephrol. 2024 Jan 9:151467. doi: 10.1016/j.semnephrol. 2023.151467. Yamada S, Tsuruya K, Kitazono T, Nakano T. Emerging cross-talks between chronic kidney disease-mineral and bone disorder (CKD-MBD) and malnutrition-inflammation complex syndrome (MICS) in patients receiving dialysis. Clin Exp Nephrol. 2022; 26:613-629. The Japanese Circulation Society. Guidelines for gender-specific cardiovascular disease（JCS2010. Circ J. 2010; 74 (suppl.11):1085-1160 (in Japanese). Tsuda T. Epidemiology of fragility fractures and fall prevention in the elderly: a systematic review of the literature. Curr Orthop Pract. 2017; 28:580-585. Kinoshita T, Ebara S, Kamimura M, Tateiwa Y, Itoh H, Yuzawa Y, et al. Nontraumatic lumbar vertebral compression fracture as a risk factor for femoral neck fractures in involutional osteoporotic patients. J Bone Miner Metab 1999;17:201-205. Dempewolf S, Mouser B, Rupe M, Owen EC, Reider L, Willey MC. What are the barriers to incorporating nutrition interventions into care of older adults with femoral fragility fractures? Iowa Orthop J. 2023;3:172-182. Bioletto F, Barale M, Maiorino F, Pusterla A, Fraire F, Arvat E, et al. Trabecular bone score as a marker of skeletal fragility across the spectrum of chronic kidney disease: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2023 December 11. doi: 10.1210/clinem/dgad724. Tables Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4022656","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":277921626,"identity":"3950ffc2-bd54-47cc-9f75-222a002c8c5b","order_by":0,"name":"Kuniyasu Takagi","email":"","orcid":"","institution":"International University of Health and Welfare Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kuniyasu","middleName":"","lastName":"Takagi","suffix":""},{"id":277921628,"identity":"ccfe732f-5685-4e5b-9566-12cad6a4bd49","order_by":1,"name":"Takuya 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critical condition\u0026nbsp;that necessitates proper\u0026nbsp;medical\u0026nbsp;intervention. Maintenance\u0026nbsp;hemodialysis is\u0026nbsp;commonly utilized\u0026nbsp;in patients with end-stage renal failure\u0026nbsp;to ensure\u0026nbsp;survival (1-3). In\u0026nbsp;Japan,\u0026nbsp;hemodialysis\u0026nbsp;is\u0026nbsp;commonly administered\u0026nbsp;to patients with end-stage renal\u0026nbsp;failure, regardless\u0026nbsp;of comorbidities, underlying diseases causing renal failure, and\u0026nbsp;age (1-3), and is covered by the universal insurance system (4,5).\u0026nbsp;According\u0026nbsp;to the Renal Data Registry of\u0026nbsp;the Japanese Society for Dialysis\u0026nbsp;Therapy,\u0026nbsp;the\u0026nbsp;prevalence\u0026nbsp;of hemodialysis\u0026nbsp;patients in Japan has\u0026nbsp;shown\u0026nbsp;a time-dependent\u0026nbsp;increase,\u0026nbsp;reaching 15 patients per 10,000\u0026nbsp;population. Additionally, it is estimated that the number of\u0026nbsp;female hemodialysispatients\u0026nbsp;is approximately half that\u0026nbsp;of male patients (3).\u003c/p\u003e\n\u003cp\u003ePatients undergoing hemodialysis commonly present\u0026nbsp;with\u0026nbsp;various\u0026nbsp;underlying diseases and comorbidities,\u0026nbsp;such as\u0026nbsp;diabetes mellitus (3,6), cardiovascular and cerebrovascular diseases (2,7,8), and malignant diseases (3).\u0026nbsp;Moreover,\u0026nbsp;the therapeutic\u0026nbsp;management of\u0026nbsp;chronic hemodialysis is\u0026nbsp;associated with various\u0026nbsp;adverse\u0026nbsp;events, including\u0026nbsp;gastrointestinal bleeding (9-12), bone fractures (13,14), infection (3,15), and cardiovascular and cerebrovascular diseases (2,7,8).\u0026nbsp;The occurrence of adverse events\u0026nbsp;may vary\u0026nbsp;between females and males, and\u0026nbsp;there is limited research focusing\u0026nbsp;on\u0026nbsp;gender differences in this area.\u003c/p\u003e\n\u003cp\u003eThis\u0026nbsp;observational\u0026nbsp;study\u0026nbsp;sought\u0026nbsp;to\u0026nbsp;investigate gender disparities in\u0026nbsp;the real-world patient characteristics\u0026nbsp;of individuals undergoing\u0026nbsp;maintenance hemodialysis at Takagi Hospital, a regional core hospital in Japan.\u0026nbsp;Significantly,\u0026nbsp;this study\u0026nbsp;examined\u0026nbsp;gender\u0026nbsp;disparities\u0026nbsp;in adverse events, gastrointestinal bleeding, and bone fractures\u0026nbsp;over\u0026nbsp;a five-year follow-up period.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis longitudinal study included 151 patients in December 2017 undergoing maintenance hemodialysis for end-stage renal failure at the Human Dialysis Center of Nephrology in Takagi Hospital, a regional core hospital in Japan (12, 16,17). All patients who received maintenance hemodialysis for end-stage renal failure at Takagi Hospital were included, and the number of patients on December 1, 2017, was 151, who were followed up for five years or until mortality (12,14). Monitoring of patients in outpatient care with blood sampling was performed every month.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData source\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients were divided into two groups: a female, 61, and a male group, 90. Patient characteristics and events, including mortality and various clinical indicators, were detected in the electronic medical record for five years until December 2022. Age, duration of hemodialysis in December 2017, the origin of renal failure, and mortality were evaluated. A patient\u0026apos;s blood test in December 2017 was detected, including hemoglobin, total protein, albumin, parathyroid hormone, iron, potassium, sodium, and calcium.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSerious complications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the five-year observation period, complications of gastrointestinal bleeding and bone fractures were detected. Gastrointestinal bleeding was determined by gastrointestinal endoscopy. All patients with signs of gastrointestinal bleeding, including melena, hematemesis, and reduction of serum hemoglobin, underwent gastrointestinal endoscopy at Takagi Hospital. Of 151 patients, 32 (21.2%: 4.2% per year) were endoscopically diagnosed with gastrointestinal bleeding. All hemodialysis patients with gastrointestinal bleeding were treated in the emergency and gastroenterology departments of Takagi Hospital. Bone fractures were diagnosed in orthopedic surgery at Takagi Hospital. Upper bone fractures included humeral fractures, radius fractures, and others. The lower bone fractures were femoral neck fractures, femoral inter- and sub-trochanteric fractures, and vertebral compression fractures. All hemodialysis patients with bone fractures were treated at the orthopedic surgery of Takagi Hospital.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted by the Declaration of Helsinki with ethical review and approval from the Takagi Hospital\u0026apos;s Kouhou-kai Ethical Committee (#495) and the International University of Health and Welfare Ethical Committee (21-Ifh-027). Written informed consent was obtained from all patients with hemodialysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBaseline characteristics\u0026nbsp;of female and male patients\u0026nbsp;were compared using the Chi-squared test for categorical variables and the Student-\u003cem\u003et\u0026nbsp;\u003c/em\u003etest for continuous variables. We applied the multiple logistic regression model with explanatory variables with significance levels (univariate \u003cem\u003eP\u003c/em\u003e value \u0026lt; 0.05 on statistical tests) except for closely gender-related factors of height and body weight.\u0026nbsp;Odds ratios and 95% confidence interval were shown in the tables. JMP Pro 16 (SAS Institute Inc., Cary, NC, USA) was used for all analyses, and statistical significance was defined as \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eCharacteristics of female patients compared with male patients.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient characteristics between female and male patients who received hemodialysis for end-stage renal failure were compared, as indicated in Table 1. The number of patients was small in females compared to males, and this difference was due to the origin of renal failure. Namely, patients of diabetes mellitus-induced renal failure were significantly less in females compared to males (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.02). The mortality rate was significantly lower in female patients compared to male patients (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.03), and low mortality in females was mainly due to the younger generation less than 75 years old (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.014), and the mortality rate in patients older than 75 years old was equivalent in females and males.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBlood test at entry on December 2017.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 shows the blood test results when the patients entered the study in December 2017. Blood samples, including hemoglobin, total protein, albumin, parathyroid hormone, iron, potassium, sodium, and calcium, were not different between females and males.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMultivariate analysis of characterized factors of female patients with hemodialysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs indicated in Table 3, multivariate analysis indicated that decreased number of diabetes mellitus patients for the origin of renal failure (odd ratio: 2.3, 95% confidence interval: 1.1-4.8, \u003cem\u003eP\u003c/em\u003e = 0.03) and less mortality in younger than 75 years old (odd ratio: 0.2, 95% confidence interval: 0.1-0.8, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.02) were independent characterized factors in female hemodialysis patients. \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGastrointestinal bleeding and bone fractures during hemodialysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4 shows the incidence of complications of gastrointestinal bleeding and bone fractures during a five-year follow-up period compared between female and male patients. Regarding upper gastrointestinal bleeding, incidence and mortality due to bleeding were not different between females and males. The incidence of lower gastrointestinal bleeding was less than that of upper gastrointestinal bleeding, and incidence and mortality were not different between females and males. The complication rate of bone fracture was high in females compared to males (females: 34.4% vs. males: 18.9%; \u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.03), whereas the mortality rate of bone fractured patients was markedly high in males compared to females (females: 28.6% vs. males: 76.5%; \u003cem\u003eP\u003c/em\u003e = 0.003). The increase in mortality rate in males was definitely in patients with lower body bone fractures (\u003cem\u003eP\u003c/em\u003e = 0.006).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe\u0026nbsp;current\u0026nbsp;five-year follow-up study\u0026nbsp;conducted at a\u0026nbsp;regional core hospital in Japan\u0026nbsp;has revealed the\u0026nbsp;clinical characteristics of female patients\u0026nbsp;undergoing\u0026nbsp;chronic hemodialysis for end-stage renal\u0026nbsp;failure, in comparison to\u0026nbsp;male\u0026nbsp;patients. Specifically, i) The incidence of end stage\u0026nbsp;renal failure\u0026nbsp;attributed to\u0026nbsp;diabetes mellitus was\u0026nbsp;lower\u0026nbsp;in females\u0026nbsp;than in\u0026nbsp;males.\u0026nbsp;ii)\u0026nbsp;Mortality rates\u0026nbsp;during hemodialysis\u0026nbsp;were lower\u0026nbsp;in females,\u0026nbsp;particularly among patients\u0026nbsp;younger than 75 years old.\u0026nbsp;iii)\u0026nbsp;The incidence of upper\u0026nbsp;and lower major gastrointestinal bleeding was\u0026nbsp;similar between\u0026nbsp;females and males.\u0026nbsp;iv)\u0026nbsp;While\u0026nbsp;bone fractures were more\u0026nbsp;common\u0026nbsp;in female patients\u0026nbsp;undergoing\u0026nbsp;hemodialysis, mortality was higher in male\u0026nbsp;patients with lower bone fractures during hemodialysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLower prevalence\u0026nbsp;of chronic hemodialysis was observed in females compared\u0026nbsp;males in the\u0026nbsp;study, which can be attributed\u0026nbsp;due\u0026nbsp;the\u0026nbsp;a\u0026nbsp;incidence\u0026nbsp;number of end-stage renal\u0026nbsp;caused by\u0026nbsp;diabetes mellitus in females. Nevertheless,\u0026nbsp;the\u0026nbsp;incidence\u0026nbsp;of hemodialysis\u0026nbsp;in patients with\u0026nbsp;nephrogenic diseases was\u0026nbsp;similar\u0026nbsp;in both genders.\u0026nbsp;This\u0026nbsp;finding\u0026nbsp;was\u0026nbsp;corroborated\u0026nbsp;by\u0026nbsp;the 2022\u0026nbsp;annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (3). In\u0026nbsp;2016, the number of\u0026nbsp;diabetes mellitus patients in Japan\u0026nbsp;was approximately\u0026nbsp;10 million,\u0026nbsp;with\u0026nbsp;female patients\u0026nbsp;accounting for\u0026nbsp;half of the male patients\u0026nbsp;due to lifestyle-related diseases (18). This gender discrepancy may\u0026nbsp;be a contributing factor tothe\u0026nbsp;lower\u0026nbsp;number of female patients\u0026nbsp;undergoing\u0026nbsp;chronic hemodialysis.\u003c/p\u003e\n\u003cp\u003eThe mortality\u0026nbsp;among individuals under\u0026nbsp;than 75\u0026nbsp;of age\u0026nbsp;old, was\u0026nbsp;higher\u0026nbsp;in male\u0026nbsp;than in\u0026nbsp;female,\u0026nbsp;while\u0026nbsp;the mortality\u0026nbsp;among those aged 75 and\u0026nbsp;the old was\u0026nbsp;similar between\u0026nbsp;in genders.\u0026nbsp;In\u0026nbsp;numerous\u0026nbsp;studies, cardiovascular and cerebrovascular\u0026nbsp;diseases, as well as infectious diseases, have been identified as\u0026nbsp;the\u0026nbsp;primary\u0026nbsp;comorbidities\u0026nbsp;associated with mortality in \u0026nbsp;hemodialysis\u0026nbsp;patients (2, 3, 7, 8, 19-21). Additionally, it has been observed that\u0026nbsp;vascular diseases are more\u0026nbsp;prevalent among male patients\u0026nbsp;in Japan (22).\u0026nbsp;The\u0026nbsp;current\u0026nbsp;study did not\u0026nbsp;precisely assess the specific causes of mortality for\u0026nbsp;each\u0026nbsp;patient, indicating a need for futher invstigation. As demonstrated\u0026nbsp;in the\u0026nbsp;current\u0026nbsp;study, bone fractures\u0026nbsp;resulted\u0026nbsp;in higher mortality\u0026nbsp;rates among\u0026nbsp;male patients compared to female patients,\u0026nbsp;potentially contributing\u0026nbsp;to gender\u0026nbsp;disparities\u0026nbsp;in mortality\u0026nbsp;among\u0026nbsp;hemodialysis patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLower\u0026nbsp;body bone fractures\u0026nbsp;including vertebral compression and femoral\u0026nbsp;fractures, along with concomitant fragility\u0026nbsp;elderly populations,\u0026nbsp;generations,\u0026nbsp;emerged as significant societal concerns\u0026nbsp;problems in Japan and\u0026nbsp;nations\u0026nbsp;countries (23-25).\u0026nbsp;As previously\u0026nbsp;shown\u0026nbsp;(26), bone fractures\u0026nbsp;pose a complex issue for\u0026nbsp;hemodialysis patients and were\u0026nbsp;found to be frequent\u0026nbsp;in the\u0026nbsp;current study, occurring\u0026nbsp;at\u0026nbsp;a rate of 27.2% over 5\u0026nbsp;years\u0026nbsp;(5.4% per year).\u0026nbsp;The\u0026nbsp;incidence\u0026nbsp;of complications from\u0026nbsp;bone fractures was\u0026nbsp;found to be higher\u0026nbsp;in female hemodialysis patients\u0026nbsp;compared to male patients, with rates of\u0026nbsp;34.4%\u0026nbsp;and 18.9% respectively.\u0026nbsp;The\u0026nbsp;mortality rate\u0026nbsp;among\u0026nbsp;hemodialysis patients with complicated lower body bone fractures was\u0026nbsp;notably\u0026nbsp;higher in male patients\u0026nbsp;(30.8% for females\u0026nbsp;vs.\u0026nbsp;84.6% for males).\u0026nbsp;The findings indicate that lower body bone fractures\u0026nbsp;may lead to significant harm, such as fragility,\u0026nbsp;in hemodialysis patients,\u0026nbsp;with a lesser impact observed\u0026nbsp;in females compared to males.\u003c/p\u003e\n\u003cp\u003eThe current\u0026nbsp;retrospective follow-up\u0026nbsp;study has several limitations.\u0026nbsp;The sample size was\u0026nbsp;limited\u0026nbsp;in the single-institution\u0026nbsp;study conducted at\u0026nbsp;the regional core hospital in Japan.\u0026nbsp;The therapeutic approach\u0026nbsp;and the\u0026nbsp;number of end-stage renal failure patients\u0026nbsp;may vary from one country to another.\u0026nbsp;The\u0026nbsp;duration\u0026nbsp;of hemodialysis treatment for the patient, spanning\u0026nbsp;five\u0026nbsp;years,\u0026nbsp;was\u0026nbsp;deemed insufficient.\u0026nbsp;It is\u0026nbsp;important\u0026nbsp;to\u0026nbsp;emphasize\u0026nbsp;that all 151 patients were closely monitored at Takagi Hospital and received comprehensive medical\u0026nbsp;attention.\u003cstrong\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eEnd-stage\u0026nbsp;renal\u0026nbsp;failure induced by diabetes mellitus\u0026nbsp;was\u0026nbsp;prevalent\u0026nbsp;frequent in females\u0026nbsp;than in males,\u0026nbsp;whereas\u0026nbsp;disease-induced renal\u0026nbsp;failure induced by nephrogenic disease\u0026nbsp;equally distributed between\u0026nbsp;in females and males.\u0026nbsp;Mortality\u0026nbsp;rates were lower among female\u0026nbsp;hemodialysis\u0026nbsp;patients, particularly those under\u0026nbsp;75 years\u0026nbsp;of age\u0026nbsp;and\u0026nbsp;those\u0026nbsp;with lower body bone\u0026nbsp;fracture complications.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to appreciate Professor Tsutomu Yamazaki, the International University of Health and Welfare Graduate School of Medicine, for invaluable advice and direction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributor roles\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMethodology and writing original draft: Kuniyasu Takagi. Methodology and supervision: Takuya Kishi and Tomohiro Imamura. Methodology: Taku Goto, Shiki Nakayama, Kohei Yamanouchi, Kazuhiko Yoshikawa, Yuichiro Akiyoshi, and Koji Onozawa. Formal analysis: Ayako Takamori. Supervision: Kazuma Fujimoto. \u003c/p\u003e\n\u003cp\u003e\u003cu\u003eEthics approval and consent to participate\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eEthical review and approval from the Takagi Hospital\u0026apos;s Kouhou-kai Ethical Committee (#495) and the International University of Health and Welfare Ethical Committee (21-Ifh-027). Written informed consent was obtained from all patients with hemodialysis.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConsent for publication\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eFunding\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAvaliability of data and materials\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eDisclosure statement\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest regarding this study.\u003cstrong\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKobayashi S, Ohtake T. The characteristics of dialysis membranes: benefits of the AN69 membrane in hemodialysis patients. J Clin Med. 2023;12:1123.\u003c/li\u003e\n\u003cli\u003eZoccali C, Mallamaci F, Adamczak M, de Oliveira RB, Massy ZA, Sarafidis P, et al. Cardiovascular complications in chronic kidney disease - a review from the European Renal and Cardiovascular Medicine Working Group of the European Renal Association. Cardiovasc Res. 2023;119:2017-2032. \u003c/li\u003e\n\u003cli\u003eHanafusa N, Abe M, Joki N, Hoshino J, Taniguchi M, Kikuchi K, et al. 2022 annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry. J Jpn Soc Dial Ther. 2023;56:473-536 (in Japanese, English abstract).\u003c/li\u003e\n\u003cli\u003eFujimoto S, Tsuruoka N, Esaki M, Takamori A, Sakata Y, Shimoda R, et al. Decline incidence in upper gastrointestinal bleeding in several recent years: data of the Japan claims database of 13 million accumulated patients. J Clin Biochem Nutr. 2021;68:95-100.\u003c/li\u003e\n\u003cli\u003eTakagi K, Matugaki R, Fujimoto K, Mine Y, Muramatsu K, Fujino Y, et al. Analysis of the risk factors of mortality in elderly patients with hip fracture using a combined database of medical and long-term care insurance claims data. J Orthop Sci. 2023;28:627-630.\u003c/li\u003e\n\u003cli\u003eMark PB, Sarafidis P, Ekart R, Ferro CJ, Balafa O, Fernandez-Fernandez B, et al. SGLT2i for evidence-based cardiorenal protection in diabetic and non-diabetic chronic kidney disease: a comprehensive review by EURECA-m and ERBP working groups of ERA. Nephrol Dial Transplant. 2023;38:2444-2455.\u003c/li\u003e\n\u003cli\u003eTobe A, Sawano M, Kohsaka S, Ishii H, Tanaka A, Numasawa Y, et al. Ischemic and bleeding outcomes in patients who underwent percutaneous coronary intervention with chronic kidney disease or dialysis (from a Japanese Nationwide Registry). Am J Cardiol. 2023;195:37-44.\u003c/li\u003e\n\u003cli\u003eKishi T, Kitajima A, Yamanouchi K, Hirooka Y, Toda S, Takamori A, et al. Low body mass index without malnutrition is an independent risk factor for major cardiovascular events in patients with hemodialysis. Int Heart J. 2022;63:948-952.\u003c/li\u003e\n\u003cli\u003eTsai TJ, Chen WC, Huang YT, Yang YH, Feng IC, Wu WC, et al. Hemodialysis increases the risk of lower gastrointestinal bleeding and angiodysplasia bleeding: a nationwide population study. Gastroenterol Res Pract. 2020;2020: 7206171.\u003c/li\u003e\n\u003cli\u003eNiikura R, Aoki T, Kojima T, Kawahara T, Tamada A, Nakamura H, et al. Natural history of upper and lower gastrointestinal bleeding in hemodialysis patients: a dual-center long-term cohort study. J Gastroenterol Hepatol. 2021;36:112-117.\u003c/li\u003e\n\u003cli\u003eKitajima A, Kishi T, Yamanouchi K, Hirooka Y, Toda S, Takamori A, et al. Retrospective analysis of risk factors for mortality during hemodialysis at the general hospital that can treat comprehensive diseases. Intern Med. 2023; 62: 1117-1121.\u003c/li\u003e\n\u003cli\u003eNakayama S, Yamanouchi K, Takamori A, Goto T, Shimada F, Imamura T, et al. Gastrointestinal bleeding among 151 patients undergoing maintenance hemodialysis for end-stage renal failure: a 5-year follow-up study. Medicine (Baltimore) 2024; 103: e37274.\u003c/li\u003e\n\u003cli\u003eGinsberg C, Ix JH. Diagnosis and management of osteoporosis in advanced kidney disease: a review. Am J Kidney Dis. 2022;79:427-436.\u003c/li\u003e\n\u003cli\u003eYoshikawa A, Kishi T, Takamori A, Kitajima A, Goto T, Nakayama S, et al. Bone fractures in the lower body have high mortality rates with hemodialysis. Ther Apher, in press\u003c/li\u003e\n\u003cli\u003eKanamori H, Weber DJ, Flythe JE, Rutala WA. Waterborne outbreaks in hemodialysis patients and infection prevention. Open Forum Infect Dis. 2022;9:ofac058.\u003c/li\u003e\n\u003cli\u003eKawaura F, Kishi T, Yamamoto T, Nakayama S, Goto T, Tsurusawa R, et al. Age distribution and disease severity of COVID-19 patients continued to change in a time-dependent manner from May 2021 to April 2022 in the regional core hospital in Japan. Drug Discov Ther. 2023;17:60-65.\u003c/li\u003e\n\u003cli\u003eMatsuo R, Imamura T, Takamori A, Kishi T, Minami M, Miyakawa J, et al. Improvement trend for individual health guidance intervention according to Japan clinical guidelines by public health nurses for type 2 diabetes mellitus individuals who visited for medical checkups regularly regardless pharmacotherapy: a case-control preliminary report. J Clin Biochem. Nutr. 2024;74:141-145.\u003c/li\u003e\n\u003cli\u003eReport of Japan Prevention Association of Lifestyle Related Disease (in Japanese) http://seikatusshukanbyo.com/statistics/disease/diabetes/ Accessed January 24, 2024\u003c/li\u003e\n\u003cli\u003eAdenwalla SF, O\u0026apos;Halloran P, Faull C, Murtagh FEM, Graham-Brown MPM. Advance care planning for patients with end-stage kidney disease on dialysis: narrative review of the current evidence, and future considerations. J Nephrol. 2024 January 18. doi: 10.1007/s40620-023-01841-3. \u003c/li\u003e\n\u003cli\u003ePonce D, Nitsch D, Ikizler TA. Strategies to Prevent Infections in Dialysis Patients. Semin Nephrol. 2024 Jan 9:151467. doi: 10.1016/j.semnephrol. 2023.151467.\u003c/li\u003e\n\u003cli\u003eYamada S, Tsuruya K, Kitazono T, Nakano T. Emerging cross-talks between chronic kidney disease-mineral and bone disorder (CKD-MBD) and malnutrition-inflammation complex syndrome (MICS) in patients receiving dialysis. Clin Exp Nephrol. 2022; 26:613-629.\u003c/li\u003e\n\u003cli\u003eThe Japanese Circulation Society. Guidelines for gender-specific cardiovascular disease（JCS2010. Circ J. 2010; 74 (suppl.11):1085-1160 (in Japanese).\u003c/li\u003e\n\u003cli\u003eTsuda T. Epidemiology of fragility fractures and fall prevention in the elderly: a systematic review of the literature. Curr Orthop Pract. 2017; 28:580-585.\u003c/li\u003e\n\u003cli\u003eKinoshita T, Ebara S, Kamimura M, Tateiwa Y, Itoh H, Yuzawa Y, et al. Nontraumatic lumbar vertebral compression fracture as a risk factor for femoral neck fractures in involutional osteoporotic patients. J Bone Miner Metab 1999;17:201-205.\u003c/li\u003e\n\u003cli\u003eDempewolf S, Mouser B, Rupe M, Owen EC, Reider L, Willey MC. What are the barriers to incorporating nutrition interventions into care of older adults with femoral fragility fractures? Iowa Orthop J. 2023;3:172-182.\u003c/li\u003e\n\u003cli\u003eBioletto F, Barale M, Maiorino F, Pusterla A, Fraire F, Arvat E, et al. Trabecular bone score as a marker of skeletal fragility across the spectrum of chronic kidney disease: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2023 December 11. doi: 10.1210/clinem/dgad724.\u003c/li\u003e\n\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1710330801.png\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1710330822.png\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1710330838.png\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1710330854.png\"\u003e\u003cbr\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"bone fracture, gastrointestinal bleeding, cardiovascular disease, cerebrovascular disease, infection, diabetes mellitus, aging, fragility","lastPublishedDoi":"10.21203/rs.3.rs-4022656/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4022656/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study aimed to evaluate gender differences in patient characteristics in maintenance hemodialysis in Takagi Hospital and, in particular, to evaluate gender differences in adverse events, gastrointestinal bleeding, and bone fractures during longitudinal follow-up period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study included 151 patients undergoing maintenance hemodialysis for end-stage renal failure at Takagi Hospital, a regional core hospital in Japan, in December 2017. All the patients were followed up for five years or until mortality with monitoring in outpatient care. All patients were divided into a female group of 61 and a male group of 90. Patient characteristics and events were evaluated in the electronic medical record including gastrointestinal bleeding and bone fractures diagnosed and treated in Takagi Hospital. Gastrointestinal bleeding was diagnosed by endoscopy. Upper bone fractures included humeral fractures and radius fractures, and lower bone fractures were femoral neck fractures and vertebral compression fractures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient number was small in females, which was due to the origin of renal failure with less frequency of diabetes mellitus (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.02). Mortality rate was significantly less in females (\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.03) of younger generations less than 75 years old (\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.014). Multivariate analysis indicated a decrease in diabetes mellitus (odd ratio: 2.3, 95% confidence interval: 1.1-4.8, \u003cem\u003eP\u003c/em\u003e = 0.03) and less mortality in those younger than 75 years old (odd ratio: 0.2, 95% confidence interval: 0.1-0.8, \u003cem\u003eP \u003c/em\u003e= 0.02) were independent characterized factors in females. Regarding adverse severe events during five years, gastrointestinal bleeding and mortality due to bleeding were not different between females and males. Bone fractures were high in females (females: 34.4% vs. males: 18.9%; \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.03), whereas the mortality rate of bone fractured patients was markedly high in males (females: 28.6% vs males: 76.5%; \u003cem\u003eP\u003c/em\u003e = 0.003). The increase in mortality rate in males was in patients with lower body bone fractures (\u003cem\u003eP\u003c/em\u003e = 0.006).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDiabetes mellitus-induced end-stage renal failure was less common in females. The mortality rate during hemodialysis was lower in females, especially in patients less than 75 years old. Lower body bone fractures exacerbated mortality more frequently in males compared to females.\u003c/p\u003e","manuscriptTitle":"Female patients with end-stage renal failure treated by hemodialysis had a low mortality rate and small patient number compared to male patients: 5-year follow-up study in Japan","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-13 11:56:27","doi":"10.21203/rs.3.rs-4022656/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ec10a18d-0b6f-44c8-9827-92de936da631","owner":[],"postedDate":"March 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-13T06:59:53+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-13 11:56:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4022656","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4022656","identity":"rs-4022656","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}