{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:18:00Z","timestamp":1791821880133,"version":"4.3.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Polypharmacy might contribute to a range of adverse outcomes, which could get worse in the elderly with chronic kidney disease (CKD). Evidence on polypharmacy, CKD, and mortality is scarce. We aimed to investigate the prospective association between polypharmacy, CKD and all-cause and cause-specific mortality in adults aged \u226565 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 13,513 adults from the National Health and Nutrition Examination Surveys were included, following up from 1999 to 2018 until December 31, 2019. The simultaneous use of \u22655 medications by one individual was defined as polypharmacy. Survey-weighted Cox proportional hazard models were used to estimate the hazard ratio (HRs) for mortality from all-cause, cardiovascular diseases (CVD), and cancer after adjusting for potential confounding factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the elderly with CKD, we identified 3,825 total deaths (1,325 CVD and 714 cancer) during a median follow-up of 7.7 years. Participants with polypharmacy had a 27% (HR\u2009=\u20091.27 [1.15, 1.39]) and 39% (HR\u2009=\u20091.39 [1.19, 1.62]) higher risk of all-cause and CVD mortality, respectively, but not for cancer mortality. Compared with the elderly with no polypharmacy and no CKD, the corresponding HRs (95%CIs) for all-cause mortality were 1.04 (0.96, 1.14) for those with no polypharmacy but CKD, 1.24 (1.11, 1.39) for with polypharmacy but no CKD, and 1.34 (1.21, 1.49) for those with both polypharmacy and CKD. A similar pattern was detected for CVD mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Polypharmacy was associated with elevated risks of all-cause and CVD mortality among the elderly CKD patients. More evidence-based approaches should be promoted for the appropriate deprescribing in the older adults with CKD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpubh.2023.1116583","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T12:35:30Z","timestamp":1679574930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Polypharmacy, chronic kidney disease, and mortality among older adults: A prospective study of National Health and nutrition examination survey, 1999\u20132018"],"prefix":"10.3389","volume":"11","author":[{"given":"Xiaowen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuantao","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Yi","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"6759521","DOI":"10.1155\/2020\/6759521","article-title":"Frailty and the risk of polypharmacy in the older person: enabling and preventative approaches","volume":"2020","author":"Nwadiugwu","year":"2020","journal-title":"J Aging Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s41999-021-00479-3","article-title":"Polypharmacy in older adults: a narrative review of definitions, epidemiology and consequences","volume":"12","author":"Pazan","year":"2021","journal-title":"Eur Geriatr Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.archger.2018.06.018","article-title":"Polypharmacy prevalence among older adults based on the survey of health, ageing and retirement in Europe","volume":"78","author":"Midao","year":"2018","journal-title":"Arch Gerontol Geriatr"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1111\/jgs.13153","article-title":"Health outcomes associated with polypharmacy in community-dwelling older adults: a systematic review","volume":"62","author":"Fried","year":"2014","journal-title":"J Am Geriatr Soc"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1001\/jamainternmed.2017.4790","article-title":"The dangers of polypharmacy in elderly patients","volume":"177","author":"Turgeon","year":"2017","journal-title":"JAMA Intern Med"},{"key":"ref6","volume-title":"Epidemiology Morbidity and Mortality","author":"Hernandez","year":"2022"},{"key":"ref7","first-page":"1","article-title":"Deaths: final data for 2013","volume":"64","author":"Xu","year":"2016","journal-title":"Natl Vital Stat Rep"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/j.japh.2017.06.002","article-title":"Association between polypharmacy and death: a systematic review and meta-analysis","volume":"57","author":"Leelakanok","year":"2003","journal-title":"J Am Pharm Assoc"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"104630","DOI":"10.1016\/j.archger.2022.104630","article-title":"Association between polypharmacy and mortality in the older adults: a systematic review and meta-analysis","volume":"100","author":"Li","year":"2022","journal-title":"Arch Gerontol Geriatr"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1093\/gerona\/glab155","article-title":"Dose-response relationships between polypharmacy and all-cause and cause-specific mortality among older people","volume":"77","author":"Huang","year":"2022","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1093\/ckj\/sfz046","article-title":"Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German chronic kidney disease study","volume":"12","author":"Schmidt","year":"2019","journal-title":"Clin Kidney J"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1093\/ndt\/gfaa164","article-title":"Drug prescription in patients with chronic kidney disease: a true challenge","volume":"36","author":"Liabeuf","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1093\/ndt\/gfaa064","article-title":"Investigators ES. International prescribing patterns and polypharmacy in older people with advanced chronic kidney disease: results from the European quality study","volume":"36","author":"Hayward","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1093\/ckj\/sfz072","article-title":"Is polypharmacy an increasing burden in chronic kidney disease? The German experience","volume":"12","author":"Parker","year":"2019","journal-title":"Clin Kidney J"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.1111\/bcp.13738","article-title":"Chronic kidney disease-renal E, information network study C. evaluation of the adequacy of drug prescriptions in patients with chronic kidney disease: results from the CKD-REIN cohort","volume":"84","author":"Laville","year":"2018","journal-title":"Br J Clin Pharmacol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.2215\/CJN.01030120","article-title":"Chronic kidney disease-renal E, information network study G. adverse drug reactions in patients with CKD","volume":"15","author":"Laville","year":"2020","journal-title":"Clin J Am Soc Nephrol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"713","DOI":"10.3390\/pharmaceutics12080713","article-title":"Prevalence of potential drug-drug interaction risk among chronic kidney disease patients in a Spanish hospital","volume":"12","author":"Santos-Diaz","year":"2020","journal-title":"Pharmaceutics"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s40266-020-00747-0","article-title":"Adverse drug events in patients with chronic kidney disease associated with multiple drug interactions and polypharmacy","volume":"37","author":"Sommer","year":"2020","journal-title":"Drugs Aging"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1093\/ndt\/gfu191","article-title":"Drugs in the elderly with chronic kidney disease: beware of potentially inappropriate medications","volume":"30","author":"Gallieni","year":"2015","journal-title":"Nephrol Dial Transplant"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s00774-021-01272-9","article-title":"Polypharmacy, chronic kidney disease, and incident fragility fracture: a prospective cohort study","volume":"40","author":"Wakasugi","year":"2022","journal-title":"J Bone Miner Metab"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.2215\/CJN.03940321","article-title":"Association of Polypharmacy with kidney disease progression in adults with CKD","volume":"16","author":"Kimura","year":"2021","journal-title":"Clin J Am Soc Nephrol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e00823","DOI":"10.1002\/prp2.823","article-title":"Polypharmacy and mortality association by chronic kidney disease status: the REasons for geographic and racial differences in stroke study","volume":"9","author":"Cashion","year":"2021","journal-title":"Pharmacol Res Perspect"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1007\/s40266-018-0563-1","article-title":"Kidney function, polypharmacy, and potentially inappropriate medication use in a community-based cohort of older adults","volume":"35","author":"Secora","year":"2018","journal-title":"Drugs Aging"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1001\/jama.2019.14745","article-title":"Chronic kidney disease diagnosis and management: a review","volume":"322","author":"Chen","year":"2019","journal-title":"JAMA"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3323","DOI":"10.1007\/s11606-020-06089-2","article-title":"Deprescribing for community-dwelling older adults: a systematic review and meta-analysis","volume":"35","author":"Bloomfield","year":"2020","journal-title":"J Gen Intern Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1038\/nrneph.2016.113","article-title":"Heart failure and kidney dysfunction: epidemiology, mechanisms and management","volume":"12","author":"Schefold","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1681\/ASN.2015050528","article-title":"PGE2, kidney disease, and cardiovascular risk: beyond hypertension and diabetes","volume":"27","author":"Nasrallah","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1093\/ajh\/hpu225","article-title":"Inflammatory cytokines and reactive oxygen species as mediators of chronic kidney disease-related vascular calcification","volume":"28","author":"Agharazii","year":"2015","journal-title":"Am J Hypertens"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/j.1472-8206.2009.00757.x","article-title":"The challenge of polypharmacy in cardiovascular medicine","volume":"24","author":"Volpe","year":"2010","journal-title":"Fundam Clin Pharmacol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e32","DOI":"10.1161\/CIR.0000000000000426","article-title":"Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association","volume":"134","author":"Page","year":"2016","journal-title":"Circulation"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"31","DOI":"10.2174\/1871525715666170529093442","article-title":"Polypharmacy in cardiovascular medicine: problems and promises!","volume":"15","author":"Abolbashari","year":"2017","journal-title":"Cardiovasc Hematol Agents Med Chem"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s10741-021-10135-4","article-title":"Polypharmacy definition and prevalence in heart failure: a systematic review","volume":"27","author":"Beezer","year":"2022","journal-title":"Heart Fail Rev"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1161\/CIRCULATIONAHA.120.050686","article-title":"Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic options","volume":"143","author":"Jankowski","year":"2021","journal-title":"Circulation"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"71","DOI":"10.5694\/mja2.50244","article-title":"Polypharmacy among older Australians, 2006-2017: a population-based study","volume":"211","author":"Page","year":"2019","journal-title":"Med J Aust"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s11606-014-2993-8","article-title":"Polypharmacy is associated with an increased risk of bleeding in elderly patients with venous thromboembolism","volume":"30","author":"Leiss","year":"2015","journal-title":"J Gen Intern Med"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"10440","DOI":"10.1038\/s41598-019-46849-7","article-title":"Risk of kidney dysfunction from polypharmacy among older patients: a nested case-control study of the south Korean senior cohort","volume":"9","author":"Kang","year":"2019","journal-title":"Sci Rep"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.jamda.2019.07.007","article-title":"Polypharmacy and kidney function in community-dwelling adults age 60 years and older: a prospective observational study","volume":"21","author":"Ernst","year":"2020","journal-title":"J Am Med Dir Assoc"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1111\/jgs.15268","article-title":"Inflammation and trajectory of renal function in community-dwelling older adults","volume":"66","author":"Salimi","year":"2018","journal-title":"J Am Geriatr Soc"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"525","DOI":"10.2217\/cpr.14.46","article-title":"Chronic kidney disease in the elderly: evaluation and management","volume":"11","author":"Mallappallil","year":"2014","journal-title":"Clin Pract (Lond)"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s40292-021-00434-0","article-title":"Diabetes, cardiovascular disease, and cardiovascular risk in patients with chronic kidney disease","volume":"28","author":"De Lima","year":"2021","journal-title":"High Blood Press Cardiovasc Prev"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1001\/jamainternmed.2019.5096","article-title":"Effect of clinical geriatric assessments and collaborative medication reviews by geriatrician and family physician for improving health-related quality of life in home-dwelling older patients receiving polypharmacy: a cluster randomized clinical trial","volume":"180","author":"Romskaug","year":"2020","journal-title":"JAMA Intern Med"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1186\/s12877-021-02612-0","article-title":"Expert-based medication reviews to reduce polypharmacy in older patients in primary care: a northern-Italian cluster-randomised controlled trial","volume":"21","author":"Mahlknecht","year":"2021","journal-title":"BMC Geriatr"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.amepre.2016.02.023","article-title":"Trends in the prevalence of coronary heart disease in the U.S.: National Health and nutrition examination survey, 2001-2012","volume":"51","author":"Yoon","year":"2016","journal-title":"Am J Prev Med"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"2389","DOI":"10.1001\/jama.2019.19365","article-title":"Prevalence of diabetes by race and ethnicity in the United States, 2011-2016","volume":"322","author":"Cheng","year":"2019","journal-title":"JAMA"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1006\/pmed.1997.0190","article-title":"Validity of self-reported hypertension in the National Health and nutrition examination survey III, 1988-1991","volume":"26","author":"Vargas","year":"1997","journal-title":"Prev Med"}],"container-title":["Frontiers in Public Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2023.1116583\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T12:35:34Z","timestamp":1679574934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2023.1116583\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,23]]},"references-count":46,"alternative-id":["10.3389\/fpubh.2023.1116583"],"URL":"https:\/\/doi.org\/10.3389\/fpubh.2023.1116583","relation":{},"ISSN":["2296-2565"],"issn-type":[{"value":"2296-2565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,23]]},"article-number":"1116583"}}