Reduced Risk of Sepsis and Related Mortality in Chronic Kidney Disease Patients on Xanthine Oxidase Inhibitors: A National Cohort Study

Frontiers in Medicine

Medicine

Hui-Tzu Tu¹  Yu-Tung Huang¹  Shang-Hung Chang²  Gerard F. Anderson³  Huang-Yu Yang⁴  Yun-Shiuan Olivia Hsu⁵  Chao-Yi Wu⁶  Hsing-Lin Lin⁷  Chih-Yen Hsiao⁸  Meng-Hsuan Hsieh⁹  Yung-Chang Chen^1,10  Chih-Wei Yang^1,10  Ya-Chong Tian^1,10  Tzung-Hai Yen^1,10  George Kuo^1,10  Chieh-Li Yen^1,10  Cheng-Chia Lee^1,10  Chung-Ying Tsai^1,10  Jia-Jin Chen^1,10  Li-Fang Chou^1,10  Tao Han Lee^1,10 

[1] Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou, Taiwan;Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou, Taiwan;Cardiovascular Department, Chang Gung Memorial Hospital at Linkou, Chang Gung University School of Medicine, Taoyuan, Taiwan;Graduate Institute of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan;Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States;Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States;Nephrology Department, Kidney Research Institute, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan;Department of Medical Education, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan;Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan;Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan;Division of Critical Care Surgery, Department of Critical Care Medicine, Veterans General Hospital, Kaohsiung, Taiwan;Division of Nephrology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan;Division of Nephrology, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan;Nephrology Department, Kidney Research Institute, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan;

关键词: chronic kidney disease;    sepsis;    MACCE;    febuxostat;    allopurinol;   

DOI  :  10.3389/fmed.2021.818132

 received in 2021-11-19, accepted in 2021-12-28,  发布年份 2022

来源: Frontiers

【 摘 要 】

BackgroundAdvanced chronic kidney disease (CKD) patients are at higher risk of sepsis-related mortality following infection and bacteremia. Interestingly, the urate-lowering febuxostat and allopurinol, both xanthine oxidase inhibitors (XOis), have been suggested to influence the sepsis course in animal studies. In this study, we aim to investigate the relationship between XOis and infection/sepsis risk in pre-dialysis population.MethodsPre-dialysis stage 5 CKD patients with gout were identified through the National Health Insurance Research Database (NHIRD) in Taiwan from 2012 to 2016. Outcomes were also compared with national data.ResultsIn our nationwide, population-based cohort study, 12,786 eligible pre-dialysis stage 5 CKD patients were enrolled. Compared to non-users, febuxostat users and allopurinol users were associated with reduced sepsis/infection risk [hazard ratio (HR), 0.93; 95% confidence interval (CI), 0.87–0.99; P = 0.0324 vs. HR, 0.92; 95% CI, 0.86–0.99; P = 0.0163]. Significant sepsis/infection-related mortality risk reduction was associated with febuxostat use (HR, 0.68; 95% CI, 0.52–0.87). Subgroup analysis demonstrated preference of febuxostat over allopurinol in sepsis/infection-related mortality among patients younger than 65 years of age, stain users, non-steroidal anti-inflammatory drug non-users, and non-diabetics. There was no significant difference in major adverse cardiac and cerebrovascular event (MACCE) risk between users and non-users while reduced risk of all-cause mortality was observed for XOi users.ConclusionsUse of XOi in pre-dialysis stage 5 CKD patients may be associated with reduced risk of sepsis/infection and their related mortality without increased MACCE and overall mortality.

【 授权许可】

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Copyright © 2022 Yang, Hsu, Lee, Wu, Tsai, Chou, Tu, Huang, Chang, Yen, Hsieh, Lee, Kuo, Hsiao, Lin, Chen, Yen, Chen, Tian, Yang and Anderson.