Trends in Renal Failure-Related Mortality among Adults in the America: A National Cross-Sectional Analysis (CDC Database Study 1999–2023)

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Its high treatment costs, resource reliance, and social impact impose a significant burden on global health systems. This study analyzes CDC WONDER data on deaths related to RF (ICD-10, N17-N19) among adults in the United States from 1999 to 2023. Age-adjusted mortality rates (AAMR) and annual percent change (APC) were calculated by year, sex, age group, race/ethnicity, geographic region, and urbanization status. A total of 1,138,750 kidney failure–related deaths were recorded between 1999 and 2023. The South had the highest cumulative deaths and the fastest-growing AAMR (AAPC = + 0.7605), while the Northeast was the only region with a declining trend (AAPC = − 0.5704). Females showed consistently higher AAMRs than males, with both sexes exhibiting slight upward trends. Non-Hispanic Whites had the highest mortality burden and a rising AAMR, while Non-Hispanic Blacks and Hispanics showed modest declines. Younger adults (ages 25–54) experienced the fastest increase in AAMR, particularly those aged 45–54 (AAPC = + 1.94). Urban residents faced a rising burden, whereas rural areas experienced slight improvements. Overall, the data indicate a steady increase in RF-related mortality, with more substantial increases observed in certain regions and populations. The trend in AAMR also shows a slight upward trajectory, suggesting an increasing burden of renal failure among specific demographics and areas. This underscores the necessity for targeted and equitable intervention strategies. renal failure epidemiology mortality racial disparity sex disparity trends Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Renal failure (RF) as the final stage of chronic kidney disease (CKD), remains a critical public health concern in the United States[ 1 ]. Despite advances in dialysis technology, transplant availability, and chronic disease management, RF continues to impose a substantial burden on both individuals and healthcare systems[ 1 – 3 ]. It is associated with high morbidity and mortality, diminished quality of life, and disproportionately high healthcare costs, particularly among populations with limited access to preventive care or early-stage CKD management[ 4 ]. Mortality attributable to RF not only reflects the biological progression of renal disease but also serves as a broader indicator of systemic health inequities[ 5 ]. Prior research has documented significant disparities in CKD prevalence and kidney failure outcomes across racial, socioeconomic, and geographic groups. These disparities are influenced by factors such as comorbidity burden, healthcare access, structural racism, and neighborhood-level social determinants of health. [ 5 ]. However, many existing studies are derived from clinical registries or Medicare-based cohorts, limiting their ability to detect emerging population-level trends, especially among younger adults or uninsured groups. In recent years, public health surveillance has increasingly highlighted concerning patterns: age-adjusted mortality rates (AAMRs) for RF appear stagnant at the national level, yet subgroup analyses suggest that specific populations—such as younger adults, residents of the Southern U.S., and individuals in metropolitan areas—may be experiencing rising mortality risks[ 6 ]. These trends have not been adequately characterized in large-scale, disaggregated longitudinal studies. To address this gap, the present study provides a comprehensive, population-based assessment of RF mortality in the United States from 1999 to 2023. Using nationally representative data, we examine AAMRs and average annual percent changes (AAPCs) across key sociodemographic and geographic subgroups, including sex, race/ethnicity, age, region, and urbanization level. Our objective is to uncover both persistent and emerging disparities in RF mortality, thereby informing more equitable and targeted public health strategies. Methodology We analyzed mortality data from the CDC WONDER database[ 7 , 8 , 9 ], focusing on adults (ages 25–85+) who died from renal failure (RF) in the United States from 1999 to 2023. Deaths related to RF were identified using ICD-10 codes N17-N19[ 9 ] from the multiple-cause public-use records database. This database and methodology have been applied in previously published studies analyzing mortality data, with data categorized by demographics, geographic location, urbanization[ 10 , 11 ], and place of death[ 12 ]. Age-adjusted mortality rates (AAMR) were calculated per 100,000 population, standardized to the 2000 U.S. population[ 13 ]. The Joinpoint regression program (version 5.4.0, National Cancer Institute)[ 14 , 15 ] was used to analyze temporal trends in AAMR, allowing for the identification of up to five inflection points over the 25-year study period. Annual percent changes (APC) and 95% confidence intervals (CI) were estimated[ 16 ], with statistical significance set at p ≤ 0.05. All data are covered by the provisions of the Public Health Service Act (42 U.S.C. 242m(d)), and ethical approval from an institutional review board was not required[ 8 , 12 ]. Results Demographic trends in mortality Census Region Between 1999 and 2023, a total of 1,138,750 deaths due to kidney failure were recorded across the United States, with substantial regional disparities. The South reported the highest cumulative mortality, accounting for 472,469 deaths (41.5% of the national total), followed by the Midwest (284,499; 25.0%) and the Northeast (228,165; 20.0%). The West had the lowest mortality burden, with 153,617 deaths (13.5%). These findings underscore a disproportionately high mortality burden in the Southern region throughout the 24-year period [17,18]. Age-adjusted mortality rates (AAMRs) revealed further differences across regions. In 1999, the South and Midwest exhibited the highest AAMRs, at 21.90 and 21.55 per 100,000 population, respectively, followed by the Northeast (20.63). The West had the lowest rate at 12.61 per 100,000. By 2023, AAMRs had increased slightly in the South (22.13) and Midwest (21.88), while the West also experienced a modest rise to 14.17. In contrast, the Northeast showed a notable decline to 19.16, making it the only region to demonstrate a downward trend over time [21]. Trends in AAMR were further assessed using average annual percent change (AAPC). The South showed the most pronounced increase (AAPC = +0.7605), indicating a persistent rise in mortality. The Midwest and West also exhibited upward trends (AAPC = +0.1926 and +0.1152, respectively), though to a lesser extent. Conversely, the Northeast was the only region with a decreasing trend (AAPC = –0.5704), suggesting potential improvements in kidney failure management and prevention [21,20,19]. Sex stratification Between 1999 and 2023, a total of 1,138,750 deaths due to kidney failure were recorded in the United States, with nearly equal distribution between sexes. Males accounted for 569,073 deaths, while females accounted for 569,677. Despite this near parity in total deaths, notable sex-specific differences were observed in age-adjusted mortality rates (AAMRs) and their temporal trends. In 1999, the AAMR for females was higher than that for males (19.57 vs. 16.61 per 100,000 population). This pattern persisted through 2023, with female AAMR rising slightly to 19.71, compared to 16.82 in males. These findings suggest a consistently greater risk of kidney failure–related mortality among females throughout the study period. In terms of temporal trends, both sexes exhibited modest increases in AAMR over the 24-year period. The average annual percent change (AAPC) was +0.1405 for males and +0.1331 for females, indicating a steady upward trajectory in mortality rates for both groups. Interestingly, when sexes were combined, the overall AAMR declined slightly from 24.70 in 1999 to 23.58 per 100,000 in 2023, with a near-zero AAPC of –0.0089. This apparent contradiction—rising AAMRs in both sexes but a declining overall trend—may reflect shifts in population age structure, geographic distribution, or other demographic modifiers that influence aggregate estimates. Racial stratification From 1999 to 2023, significant racial disparities were observed in kidney failure–related mortality across the United States. Of the total 1,138,255 recorded deaths, Non-Hispanic Whites (NH Whites) accounted for the majority, with 813,791 deaths (71.5%). Non-Hispanic Blacks (NH Blacks) reported 209,844 deaths (18.4%), followed by Hispanics (77,262; 6.8%) and Non-Hispanic Others (NH Others) with 35,358 deaths (3.1%). In 1999, NH Whites had the highest age-adjusted mortality rate (AAMR), at 43.31 per 100,000 population, far exceeding that of NH Blacks (17.94), Hispanics (17.17), and NH Others (15.91). By 2023, the AAMR in NH Whites declined modestly to 39.39, but remained substantially higher than all other racial groups. AAMRs for NH Blacks (17.97) and Hispanics (17.69) remained relatively stable, while NH Others experienced a decline to 14.04, representing the lowest mortality burden among all groups. Temporal trends, as reflected by average annual percent change (AAPC), revealed further differences. Despite their already high mortality rate, NH Whites continued to show an upward trend in AAMR (AAPC = +0.2211). NH Others also experienced a slight increase (AAPC = +0.0582). In contrast, both Hispanics (AAPC = –0.3150) and NH Blacks (AAPC = –0.3055) showed modest downward trends, suggesting some improvement in mortality outcomes for these populations over the study period. Age-wise distribution Between 1999 and 2023, kidney failure–related mortality in the United States exhibited clear age-related patterns, with mortality burden increasing markedly with advancing age. Individuals aged 65–74 years accounted for the highest number of deaths (218,258; 19.2% of total), followed by those aged 55–64 years (118,151), 45–54 years (51,532), 35–44 years (18,395), and 25–34 years (6,329). These data indicate that kidney failure remains predominantly a condition of older adults. Age-adjusted mortality rates (AAMRs) revealed a different temporal trend across age groups. Although the 65–74 age group had the highest AAMR in both years, it slightly declined from 36.36 per 100,000 in 1999 to 34.71 in 2023, with an average annual percent change (AAPC) of –0.0941. In contrast, younger and middle-aged groups showed consistent increases in AAMR. The most rapid rise was observed in the 45–54 age group, with AAMR increasing from 3.89 to 5.93 per 100,000 and an AAPC of +1.9414. Similarly, AAMRs in the 35–44 and 25–34 age groups increased from 1.49 to 2.02 (AAPC = +1.4573) and from 0.57 to 0.74 (AAPC = +1.0644), respectively. The 55–64 age group also experienced a rise, from 11.71 to 14.53 (AAPC = +1.0021). Urbanization From 1999 to 2023, substantial disparities in kidney failure–related mortality were observed between metropolitan and nonmetropolitan areas in the United States. Of the 974,936 deaths recorded during this period, the majority occurred in metropolitan areas (775,871; 79.6%), while nonmetropolitan areas accounted for 199,065 deaths (20.4%). These findings indicate that although the absolute burden is concentrated in urban regions, rural areas still contribute a significant share to national kidney failure mortality. In 1999, the age-adjusted mortality rate (AAMR) was higher in metropolitan areas (21.41 per 100,000 population) than in nonmetropolitan areas (19.11 per 100,000). Although 2023 AAMR data were not available, longitudinal trends assessed using the average annual percent change (AAPC) provide insight into the overall direction of mortality risk. The AAMR in metropolitan areas showed a rising trend (AAPC = +0.3065), while nonmetropolitan areas experienced a modest decline (AAPC = –0.1755). This divergence suggests increasing mortality risk in urban settings over time, in contrast to a slight improvement in rural regions. Discussion This study offers a comprehensive, population-level analysis of kidney failure–related mortality in the United States over a 24-year period, revealing a complex and uneven trajectory shaped by geographic, demographic, and structural factors. While the overall age-adjusted mortality rate (AAMR) remained largely stable at the national level, substantial heterogeneity was observed across subgroups, exposing critical disparities that may be masked by aggregated trends. [ 18 , 19 ] Striking regional and urban–rural disparities persist. The South and West experienced the steepest increases in both mortality counts and AAMR, with the West showing a statistically significant upward trend (AAPC = + 0.76%, 95% CI: +0.08 to + 1.44). In contrast, the Northeast was the only region to exhibit a significant decline in AAMR (AAPC = − 0.57%, 95% CI: − 0.89 to − 0.25), potentially reflecting more robust chronic disease management infrastructure or earlier intervention practices. Notably, despite presumed advantages in care access, nonmetropolitan areas saw a significant rise in AAMR, suggesting that rural kidney health outcomes may be deteriorating due to resource constraints, workforce shortages, or delayed diagnosis. [ 17 – 19 , 22 ] Age-stratified trends revealed a concerning generational shift. The fastest AAMR increases were concentrated among younger and middle-aged adults, particularly those aged 45–54 (AAPC = + 1.94%, 95% CI: +1.21 to + 2.68). This shift may be attributed to the rising prevalence of modifiable risk factors such as obesity, diabetes, and hypertension in younger populations, as well as lower rates of screening and awareness. These findings challenge the conventional framing of kidney failure as a disease primarily affecting older adults and emphasize the urgency of integrating CKD screening into routine care for younger age groups. [ 23 – 25 ] Racial and ethnic patterns presented a mixed picture. While Non-Hispanic Whites continued to bear the largest absolute burden, their AAMR increased modestly without reaching statistical significance. In contrast, AAMRs among Non-Hispanic Blacks and Hispanics remained stable or slightly declined, possibly reflecting early benefits of targeted interventions and public health efforts in historically underserved communities. However, the disproportionately large increases in absolute deaths among Hispanic and Non-Hispanic Other populations underscore the need for culturally and linguistically tailored outreach, particularly as these groups grow rapidly within the U.S. population. [ 2 , 5 , 17 ] Sex-based differences remained modest but important. While males maintained higher AAMRs than females, trends over time were largely flat for both sexes, and no statistically significant AAPC was observed. These patterns suggest that sex-based disparities in kidney failure mortality may be less dynamic than other forms of inequity, but nonetheless warrant continued monitoring—particularly in the context of differential disease awareness, health-seeking behavior, and treatment adherence. [ 21 ] Taken together, these findings point to an evolving landscape in kidney failure mortality—one in which the burden is increasingly concentrated among younger adults, urban and Southern populations, and socioeconomically marginalized groups. The stagnation or deterioration of mortality rates in these subgroups highlights the limitations of current population-level strategies and underscores the importance of tailored interventions. Expanding access to early CKD screening, strengthening nephrology capacity in high-risk areas, and integrating community-based prevention initiatives will be essential to reverse these trends. [ 26 – 28 ] In sum, the stability of national renal‑failure mortality masks concentrated increases among specific subpopulations and places. A prevention‑to‑treatment strategy—spanning early risk detection, optimized CKM care, robust post‑AKI follow‑up, and equitable access to advanced therapies—offers a realistic path to reverse these patterns. [ 1 , 29 , 30 ] Future work should link mortality to longitudinal clinical or claims data to explore patient‑level pathways from CKM risk factors through CKD onset, AKI episodes, and terminal events. Integrating geospatial measures of social deprivation, food and pharmacy access, and environmental stressors would help target interventions. Pragmatic trials and implementation studies in high‑burden communities are essential to translate epidemiologic insight into durable mortality reductions. [ 17 , 18 ] Our analysis has notable strengths: population‑based coverage, long time horizon, standardized age adjustment, and subgroup resolution by region, urbanicity, sex, age, and race/ethnicity. Limitations include potential misclassification in death certificates; lack of granular clinical, behavioral, and environmental covariates; small‑cell suppression affecting county‑level stability; and residual confounding. These constraints mean our estimates should be interpreted as indicators of population burden rather than precise causal effects. At the system level, high-burden regions—particularly the South—require expanded nephrology capacity, integrated cardio-kidney-metabolic (CKM) care models, and community health worker programs to improve treatment adherence. Equity-focused strategies must address barriers like language access, transportation, and insurance coverage to ensure timely referrals for dialysis education and transplant evaluation. [ 26 – 28 ] From a clinical perspective, the rising mortality among younger adults underscores the need for earlier CKD detection and aggressive CKM risk management in primary care. Key steps include routine eGFR and albuminuria screening for high-risk individuals, tighter control of blood pressure and glycemia, and timely initiation of kidney-protective therapies. Strengthening post-AKI care transitions is also critical to reduce short-term mortality and slow disease progression. [ 30 ] Methodologically, several extensions could strengthen future work. Beyond Joinpoint models, age–period–cohort or negative binomial regressions could separate cohort effects from period shocks. [ 31 ]State‑ and county‑level mixed‑effects models with social‑determinant covariates (income, educational attainment, insurance expansion, environmental exposures such as extreme heat and air pollution) would help quantify structural contributors. Disaggregating N17, N18, and N19 could clarify whether trends are driven by acute events, chronic progression, or certification ambiguity. Data and methodological considerations must be acknowledged. The COVID-19 pandemic may have perturbed both kidney failure incidence—through virus-associated AKI and deferred care—and cause-of-death certification patterns, necessitating cautious interpretation of 2020–2021 trends[ 31 , 32 ].Furthermore, variations in death certification across jurisdictions and demographic groups can alter recorded mortality without reflecting true changes in burden, an issue only partially mitigated by multiple-cause mortality data. Key epidemiological trends reveal critical drivers of kidney failure mortality. The pronounced rise among adults aged 35–54 suggests a cohort effect of accelerating cardio-kidney-metabolic risk, likely driven by earlier onset of obesity and diabetes, suboptimal risk factor control, and delayed detection. Concurrently, persistent geographic and urban–rural disparities align with established gradients in comorbidities and healthcare access, though the declining trend in the Northeast demonstrates the potential of integrated chronic disease management to curb mortality [ 33 , 34 ]. Conclusion This nationwide analysis reveals that kidney failure mortality remains a significant and unequal public health burden in the United States. Rising risks among younger adults, metropolitan populations, and Southern residents demand urgent, tailored interventions. Policies must be guided by disaggregated data and committed to advancing health equity in kidney care. Declarations Ethical approval No ethical approval was required for this study design, as all data were obtained from publicly available sources. Consent Informed consent was not required as we utilized data from a de-identified government-provided public use dataset. Funding None Author contribution Yong Ding: Contributed equally to the conception, design of the study, data collection and drafting of the manuscript. Chang Chen, Bingjie Yang, Kangkang Ding: Participated in data analysis and manuscript revision.He Wang (corresponding author): Supervised the entire study, revised the manuscript critically, and approved the final version for publication. Conflict of Interest The authors declare no conflicts of interest. Data availability statement The data supporting the findings of this study are openly available in CDC Wonder at [https://wonder.cdc.gov/]. References Levin A, Ahmed SB, Carrero JJ, et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int. 2024 Apr;105(4):684-701. PMID: 38519239. Johansen KL, Chertow GM, Foley RN, et al. US Renal Data System 2020 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2021 Apr;77(4 Suppl 1):A7-A8. PMID: 33752804; PMCID: PMC8148988. Bello AK, Okpechi IG, Osman MA, et al. Epidemiology of haemodialysis outcomes. Nat Rev Nephrol. 2022 Jun;18(6):378-395. PMID: 35194215; PMCID: PMC8862002. Stewart F, Kistler K, Du Y, Singh RR, Dean BB, Kong SX. Exploring kidney dialysis costs in the United States: a scoping review. J Med Econ. 2024;27(1):618-625. PMID: 38605648. Norton JM, Moxey-Mims MM, Eggers PW, Narva AS, Star RA, Kimmel PL, Rodgers GP. Social Determinants of Racial Disparities in CKD. J Am Soc Nephrol. 2016 Sep;27(9):2576-2595. PMID: 27178804; PMCID: PMC5004663. Mokdad AH, Dwyer-Lindgren L, Bertozzi-Villa A, et al. Trends and patterns of disparities in diabetes and chronic kidney disease mortality among US counties, 1980–2014. Popul Health Metr. 2022 Feb 22;20(1):9. PMID: 35193593; PMCID: PMC8862531. Tiwari, C., K. Beyer, and G. Rushton, The impact of data suppression on local mortality rates: the case of CDC WONDER. Am J Public Health, 2014. 104(8): p. 1386-8. Rashid AM, Zhao X, Li X, et al. Trends in mortality related to kidney failure and diabetes mellitus in the United States: a 1999–2020 analysis. Endocrinol Diabetes Metab. 2024;7(4):e493. PMID: 38916852; PMCID: PMC11519297. Chen Z, Fu X, Wang J, et al. Kidney failure-related excess mortality during the first three years of the pandemic in the United States. BMC Public Health. 2025;25:21422. PMCID: PMC11745008. Ingram DD, Franco SJ. 2013 NCHS Urban–Rural Classification Scheme for Counties. Vital Health Stat 2. 2014;(166):1–73. PMID: 24776070. Ingram DD, Franco SJ. 2006 NCHS Urban–Rural Classification Scheme for Counties. Vital Health Stat 2. 2012;(154):1–65. PMID: 22783637. Cross SH, Kaufman BG, Warraich HJ, Taylor DH Jr. Trends in place of death for individuals with advanced kidney disease in the United States, 2003–2017. J Pain Symptom Manage. 2021;61(1):36–44. PMID: 32791183. Anderson RN, Rosenberg HM. Age standardization of death rates: implementation of the year 2000 standard. Natl Vital Stat Rep. 1998;47(3):1–16, 20. PMID: 9796247. Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19(3):335–351. PMID: 10649300. Kim HJ, Howlader N, Enewold L, et al. Twenty years since Joinpoint 1.0: two major extensions of the model. Cancer Res Stat Treat. 2022;5(3):463–472. PMID: 35522060. Clegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK. Estimating average annual percent change in trend analysis. Stat Med. 2009;28(29):3670–3682. PMID: 19856324. Snow KK, Patzer RE, Patel SA, et al. County-Level Characteristics Associated With Variation in End-Stage Kidney Disease Mortality in the United States, 2010–2018. Kidney360. 2022;3(9):1554–1565. PMID: 36128479; PMCID: PMC9438422. Mokdad AH, Dwyer-Lindgren L, Bertozzi-Villa A, et al. Trends and patterns of disparities in diabetes and chronic kidney disease mortality among US counties, 1980–2014. Popul Health Metr. 2022;20(1):9. PMID: 35193593; PMCID: PMC8862531. Dwyer-Lindgren L, Bertozzi-Villa A, Stubbs RW, et al. US County-Level Trends in Mortality Rates for Major Causes of Death, 1980–2014. JAMA. 2016;316(22):2385–2401. PMID: 27959996; PMCID: PMC5576343. Raja A, Raja S, Amin SB, et al. Temporal trends in hypertension-related end-stage renal disease mortality rates: analysis by gender, race/ethnicity, and census region in the United States, 1999–2020. Front Nephrol. 2024;3:1339312. PMID: 38288382. Grobman B, Azeem B, Khan A, et al. Trends and Disparities in Deaths from Kidney Disease Among Older Adults in the United States. J Clin Med. 2025;14(14):4950. PMID: 40725643; PMCID: PMC12295388. Xu F, Stewart AJ, Khanam MA, Decloedt EH, Al ence S, Qayed E, et al. Urban–rural differences in acute kidney injury mortality in the United States. Am J Prev Med. 2025. PMID: 39179183. Ellison-Barnes A, Johnson S, Gudzune KA. Trends in Obesity Prevalence Among Adults Aged 18 Through 25 Years, 1976–2018. JAMA. 2021;326(20):2073–2074. PMID: 34812876. Hardy ST, Hardy RJ, Harrell FE Jr, et al. Trends in Blood Pressure Control Among US Adults, 1999–2020. JAMA. 2024. PMID: 38254218. Tang O, Vaidya A, Kline A, et al. Hypertension Awareness, Treatment, and Control Among Young Adults in the United States, 2011–2020. Hypertension. 2024. PMID: 40156902. Ndumele CE, Rangaswami J, Chow SL, et al.; American Heart Association. Cardiovascular–Kidney–Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023;148(20):1606–1635. PMID: 37807924. Victor RG, Lynch K, Li N, et al. A Cluster-Randomized Trial of Blood-Pressure Reduction in Black Barbershops. N Engl J Med. 2018;378(14):1296–1308. PMID: 29527973. Islam NS, Wyatt LC, Kwon SC, et al. Integrating Community Health Workers Into Community-Based Primary Care Practice Settings to Improve Blood Pressure Control Among South Asian Immigrants in New York City: Results From a Randomized Control Trial. Circ Cardiovasc Qual Outcomes. 2023;16(3):e009321. PMID: 36815464. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al.; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436–1446. PMID: 32970396. Herrington WG, Staplin N, Judge PK, et al.; EMPA-KIDNEY Collaborative Group. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023. PMID: 36331190. Hirsch JS, Ng JH, Ross DW, et al.; Northwell COVID-19 Research Consortium. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020. PMID: 32416116. Chan L, Chaudhary K, Saha A, et al. AKI in Hospitalized Patients with COVID-19. J Am Soc Nephrol. 2021;32(1):151–160. PMID: 32883700. Mieno MN, Tanaka N, Arai T, et al. Accuracy of Death Certificates and Assessment of Factors for Misclassification of Underlying Cause of Death. J Epidemiol. 2016;26(4):191–198. PMID: 26639750. Harel Z, Wald R, Bargman JM, et al. Nephrologist Follow-up Improves All-Cause Mortality of Patients With Severe Acute Kidney Injury. Kidney Int. 2013;83(5):901–908. PMID: 23325077. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 Jan, 2026 Read the published version in BMC Public Health → Version 1 posted Editorial decision: Revision requested 22 Dec, 2025 Reviews received at journal 20 Dec, 2025 Reviews received at journal 19 Dec, 2025 Reviewers agreed at journal 19 Dec, 2025 Reviewers agreed at journal 13 Dec, 2025 Reviewers agreed at journal 26 Nov, 2025 Reviewers agreed at journal 24 Nov, 2025 Reviewers agreed at journal 24 Nov, 2025 Reviewers agreed at journal 21 Nov, 2025 Reviews received at journal 20 Nov, 2025 Reviewers agreed at journal 20 Nov, 2025 Reviewers invited by journal 19 Nov, 2025 Editor invited by journal 11 Nov, 2025 Editor assigned by journal 11 Nov, 2025 Submission checks completed at journal 11 Nov, 2025 First submitted to journal 10 Nov, 2025 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. 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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-8074626","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":551420074,"identity":"e8ea1662-6f0d-4c17-92e8-fa3d8b10de30","order_by":0,"name":"Yong Ding","email":"","orcid":"","institution":"The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yong","middleName":"","lastName":"Ding","suffix":""},{"id":551420075,"identity":"5ba32cd8-2d1a-402f-b24f-9515488d6daf","order_by":1,"name":"Chang Chen","email":"","orcid":"","institution":"The 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12:36:19","extension":"html","order_by":29,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":88904,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8074626/v1/3dd2f561acb2a40e7579061f.html"},{"id":96919955,"identity":"fa147dc2-9afc-45d5-a9de-b3926c6ab3c6","added_by":"auto","created_at":"2025-11-27 14:14:39","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":163401,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGeographic Patterns and Temporal Trends in Kidney Failure Mortality in the United States, 1999–2023. (A) Total number of kidney failure–related deaths by state. (B) Age-adjusted mortality rates (AAMR) in 2023. (C) Percent change in total deaths from 1999 to 2023. (D) Average annual percent change (AAPC) in AAMR.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074626/v1/e49ec4ad51ade8197d507381.jpeg"},{"id":96907003,"identity":"bdc9fc7d-3786-4c0c-aff7-a6626ed48523","added_by":"auto","created_at":"2025-11-27 12:36:18","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":153969,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRF-related age-adjusted mortality rates per 100 000, stratified by census region in adults in the United States, 1999–2023. *Indicates that the annual percentage change (APC) is significantly different from zero at α = 0.05.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074626/v1/a22f6529cceb7b99bb698b43.jpeg"},{"id":96907004,"identity":"13534db9-8f6f-4850-bea5-439ec6443e36","added_by":"auto","created_at":"2025-11-27 12:36:18","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":118682,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRF-related age-adjusted mortality rates per 100 000, stratified by sex in adults in the United States, 1999–2023. *Indicates that the annual percentage change (APC) is significantly different from zero at α = 0.05.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074626/v1/2199ae37db9abb9277b2f04a.jpeg"},{"id":96921050,"identity":"927a37b8-ff94-43f9-8731-15e5b8425935","added_by":"auto","created_at":"2025-11-27 14:15:37","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":121924,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRF-related age-adjusted mortality rates per 100 000, stratified by race in adults in the United States, 1999–2023. *Indicates that the annual percentage change (APC) is significantly different from zero at α = 0.05. NH, non-Hispanic.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074626/v1/fb8ed6ffd622e98548f99f0e.jpeg"},{"id":96921108,"identity":"d2b68e22-a588-476b-8cc0-e95a511a5afb","added_by":"auto","created_at":"2025-11-27 14:15:43","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":110613,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRF-related age-adjusted mortality rates per 100 000, stratified by age in adults in the United States, 1999–2023. *Indicates that the annual percentage change (APC) is significantly different from zero at α = 0.05.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074626/v1/85f69cd7b59f0f89137272a1.jpeg"},{"id":96907008,"identity":"527af010-1456-4204-a8e0-b02da976db6f","added_by":"auto","created_at":"2025-11-27 12:36:18","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":101648,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRF-related age-adjusted mortality rates per 100 000, stratified by urbanization in adults in the United States, 1999–2023. *Indicates that the annual percentage change (APC) is significantly different from zero at α = 0.05.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074626/v1/0d93d84799190a2ed6381a7d.jpeg"},{"id":101152039,"identity":"e5ec760a-a676-4c31-a33f-4c2da193ca41","added_by":"auto","created_at":"2026-01-26 16:09:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1683713,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8074626/v1/f918e260-167e-4c64-800b-2a16c5488c9a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Trends in Renal Failure-Related Mortality among Adults in the America: A National Cross-Sectional Analysis (CDC Database Study 1999–2023)","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRenal failure (RF) as the final stage of chronic kidney disease (CKD), remains a critical public health concern in the United States[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Despite advances in dialysis technology, transplant availability, and chronic disease management, RF continues to impose a substantial burden on both individuals and healthcare systems[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It is associated with high morbidity and mortality, diminished quality of life, and disproportionately high healthcare costs, particularly among populations with limited access to preventive care or early-stage CKD management[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMortality attributable to RF not only reflects the biological progression of renal disease but also serves as a broader indicator of systemic health inequities[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Prior research has documented significant disparities in CKD prevalence and kidney failure outcomes across racial, socioeconomic, and geographic groups. These disparities are influenced by factors such as comorbidity burden, healthcare access, structural racism, and neighborhood-level social determinants of health. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, many existing studies are derived from clinical registries or Medicare-based cohorts, limiting their ability to detect emerging population-level trends, especially among younger adults or uninsured groups.\u003c/p\u003e\u003cp\u003eIn recent years, public health surveillance has increasingly highlighted concerning patterns: age-adjusted mortality rates (AAMRs) for RF appear stagnant at the national level, yet subgroup analyses suggest that specific populations\u0026mdash;such as younger adults, residents of the Southern U.S., and individuals in metropolitan areas\u0026mdash;may be experiencing rising mortality risks[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. These trends have not been adequately characterized in large-scale, disaggregated longitudinal studies.\u003c/p\u003e\u003cp\u003eTo address this gap, the present study provides a comprehensive, population-based assessment of RF mortality in the United States from 1999 to 2023. Using nationally representative data, we examine AAMRs and average annual percent changes (AAPCs) across key sociodemographic and geographic subgroups, including sex, race/ethnicity, age, region, and urbanization level. Our objective is to uncover both persistent and emerging disparities in RF mortality, thereby informing more equitable and targeted public health strategies.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003eWe analyzed mortality data from the CDC WONDER database[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], focusing on adults (ages 25\u0026ndash;85+) who died from renal failure (RF) in the United States from 1999 to 2023. Deaths related to RF were identified using ICD-10 codes N17-N19[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] from the multiple-cause public-use records database. This database and methodology have been applied in previously published studies analyzing mortality data, with data categorized by demographics, geographic location, urbanization[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and place of death[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Age-adjusted mortality rates (AAMR) were calculated per 100,000 population, standardized to the 2000 U.S. population[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The Joinpoint regression program (version 5.4.0, National Cancer Institute)[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] was used to analyze temporal trends in AAMR, allowing for the identification of up to five inflection points over the 25-year study period. Annual percent changes (APC) and 95% confidence intervals (CI) were estimated[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], with statistical significance set at p\u0026thinsp;\u0026le;\u0026thinsp;0.05. All data are covered by the provisions of the Public Health Service Act (42 U.S.C. 242m(d)), and ethical approval from an institutional review board was not required[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDemographic trends in mortality\u003c/p\u003e\n\u003cp\u003eCensus Region\u003c/p\u003e\n\u003cp\u003eBetween 1999 and 2023, a total of 1,138,750 deaths due to kidney failure were recorded across the United States, with substantial regional disparities. The South reported the highest cumulative mortality, accounting for 472,469 deaths (41.5% of the national total), followed by the Midwest (284,499; 25.0%) and the Northeast (228,165; 20.0%). The West had the lowest mortality burden, with 153,617 deaths (13.5%). These findings underscore a disproportionately high mortality burden in the Southern region throughout the 24-year period [17,18].\u003c/p\u003e\n\u003cp\u003eAge-adjusted mortality rates (AAMRs) revealed further differences across regions. In 1999, the South and Midwest exhibited the highest AAMRs, at 21.90 and 21.55 per 100,000 population, respectively, followed by the Northeast (20.63). The West had the lowest rate at 12.61 per 100,000. By 2023, AAMRs had increased slightly in the South (22.13) and Midwest (21.88), while the West also experienced a modest rise to 14.17. In contrast, the Northeast showed a notable decline to 19.16, making it the only region to demonstrate a downward trend over time [21].\u003c/p\u003e\n\u003cp\u003eTrends in AAMR were further assessed using average annual percent change (AAPC). The South showed the most pronounced increase (AAPC = +0.7605), indicating a persistent rise in mortality. The Midwest and West also exhibited upward trends (AAPC = +0.1926 and +0.1152, respectively), though to a lesser extent. Conversely, the Northeast was the only region with a decreasing trend (AAPC = \u0026ndash;0.5704), suggesting potential improvements in kidney failure management and prevention [21,20,19].\u003c/p\u003e\n\u003cp\u003eSex stratification\u003c/p\u003e\n\u003cp\u003eBetween 1999 and 2023, a total of 1,138,750 deaths due to kidney failure were recorded in the United States, with nearly equal distribution between sexes. Males accounted for 569,073 deaths, while females accounted for 569,677. Despite this near parity in total deaths, notable sex-specific differences were observed in age-adjusted mortality rates (AAMRs) and their temporal trends.\u003c/p\u003e\n\u003cp\u003eIn 1999, the AAMR for females was higher than that for males (19.57 vs. 16.61 per 100,000 population). This pattern persisted through 2023, with female AAMR rising slightly to 19.71, compared to 16.82 in males. These findings suggest a consistently greater risk of kidney failure\u0026ndash;related mortality among females throughout the study period.\u003c/p\u003e\n\u003cp\u003eIn terms of temporal trends, both sexes exhibited modest increases in AAMR over the 24-year period. The average annual percent change (AAPC) was +0.1405 for males and +0.1331 for females, indicating a steady upward trajectory in mortality rates for both groups. Interestingly, when sexes were combined, the overall AAMR declined slightly from 24.70 in 1999 to 23.58 per 100,000 in 2023, with a near-zero AAPC of \u0026ndash;0.0089. This apparent contradiction\u0026mdash;rising AAMRs in both sexes but a declining overall trend\u0026mdash;may reflect shifts in population age structure, geographic distribution, or other demographic modifiers that influence aggregate estimates.\u003c/p\u003e\n\u003cp\u003eRacial stratification\u003c/p\u003e\n\u003cp\u003eFrom 1999 to 2023, significant racial disparities were observed in kidney failure\u0026ndash;related mortality across the United States. Of the total 1,138,255 recorded deaths, Non-Hispanic Whites (NH Whites) accounted for the majority, with 813,791 deaths (71.5%). Non-Hispanic Blacks (NH Blacks) reported 209,844 deaths (18.4%), followed by Hispanics (77,262; 6.8%) and Non-Hispanic Others (NH Others) with 35,358 deaths (3.1%).\u003c/p\u003e\n\u003cp\u003eIn 1999, NH Whites had the highest age-adjusted mortality rate (AAMR), at 43.31 per 100,000 population, far exceeding that of NH Blacks (17.94), Hispanics (17.17), and NH Others (15.91). By 2023, the AAMR in NH Whites declined modestly to 39.39, but remained substantially higher than all other racial groups. AAMRs for NH Blacks (17.97) and Hispanics (17.69) remained relatively stable, while NH Others experienced a decline to 14.04, representing the lowest mortality burden among all groups.\u003c/p\u003e\n\u003cp\u003eTemporal trends, as reflected by average annual percent change (AAPC), revealed further differences. Despite their already high mortality rate, NH Whites continued to show an upward trend in AAMR (AAPC = +0.2211). NH Others also experienced a slight increase (AAPC = +0.0582). In contrast, both Hispanics (AAPC = \u0026ndash;0.3150) and NH Blacks (AAPC = \u0026ndash;0.3055) showed modest downward trends, suggesting some improvement in mortality outcomes for these populations over the study period.\u003c/p\u003e\n\u003cp\u003eAge-wise distribution\u003c/p\u003e\n\u003cp\u003eBetween 1999 and 2023, kidney failure\u0026ndash;related mortality in the United States exhibited clear age-related patterns, with mortality burden increasing markedly with advancing age. Individuals aged 65\u0026ndash;74 years accounted for the highest number of deaths (218,258; 19.2% of total), followed by those aged 55\u0026ndash;64 years (118,151), 45\u0026ndash;54 years (51,532), 35\u0026ndash;44 years (18,395), and 25\u0026ndash;34 years (6,329). These data indicate that kidney failure remains predominantly a condition of older adults.\u003c/p\u003e\n\u003cp\u003eAge-adjusted mortality rates (AAMRs) revealed a different temporal trend across age groups. Although the 65\u0026ndash;74 age group had the highest AAMR in both years, it slightly declined from 36.36 per 100,000 in 1999 to 34.71 in 2023, with an average annual percent change (AAPC) of \u0026ndash;0.0941. In contrast, younger and middle-aged groups showed consistent increases in AAMR. The most rapid rise was observed in the 45\u0026ndash;54 age group, with AAMR increasing from 3.89 to 5.93 per 100,000 and an AAPC of +1.9414. Similarly, AAMRs in the 35\u0026ndash;44 and 25\u0026ndash;34 age groups increased from 1.49 to 2.02 (AAPC = +1.4573) and from 0.57 to 0.74 (AAPC = +1.0644), respectively. The 55\u0026ndash;64 age group also experienced a rise, from 11.71 to 14.53 (AAPC = +1.0021).\u003c/p\u003e\n\u003cp\u003eUrbanization\u003c/p\u003e\n\u003cp\u003eFrom 1999 to 2023, substantial disparities in kidney failure\u0026ndash;related mortality were observed between metropolitan and nonmetropolitan areas in the United States. Of the 974,936 deaths recorded during this period, the majority occurred in metropolitan areas (775,871; 79.6%), while nonmetropolitan areas accounted for 199,065 deaths (20.4%). These findings indicate that although the absolute burden is concentrated in urban regions, rural areas still contribute a significant share to national kidney failure mortality.\u003c/p\u003e\n\u003cp\u003eIn 1999, the age-adjusted mortality rate (AAMR) was higher in metropolitan areas (21.41 per 100,000 population) than in nonmetropolitan areas (19.11 per 100,000). Although 2023 AAMR data were not available, longitudinal trends assessed using the average annual percent change (AAPC) provide insight into the overall direction of mortality risk. The AAMR in metropolitan areas showed a rising trend (AAPC = +0.3065), while nonmetropolitan areas experienced a modest decline (AAPC = \u0026ndash;0.1755). This divergence suggests increasing mortality risk in urban settings over time, in contrast to a slight improvement in rural regions.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study offers a comprehensive, population-level analysis of kidney failure\u0026ndash;related mortality in the United States over a 24-year period, revealing a complex and uneven trajectory shaped by geographic, demographic, and structural factors. While the overall age-adjusted mortality rate (AAMR) remained largely stable at the national level, substantial heterogeneity was observed across subgroups, exposing critical disparities that may be masked by aggregated trends. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eStriking regional and urban\u0026ndash;rural disparities persist. The South and West experienced the steepest increases in both mortality counts and AAMR, with the West showing a statistically significant upward trend (AAPC\u0026thinsp;=\u0026thinsp;+\u0026thinsp;0.76%, 95% CI: +0.08 to +\u0026thinsp;1.44). In contrast, the Northeast was the only region to exhibit a significant decline in AAMR (AAPC = \u0026minus;\u0026thinsp;0.57%, 95% CI: \u0026minus;\u0026thinsp;0.89 to \u0026minus;\u0026thinsp;0.25), potentially reflecting more robust chronic disease management infrastructure or earlier intervention practices. Notably, despite presumed advantages in care access, nonmetropolitan areas saw a significant rise in AAMR, suggesting that rural kidney health outcomes may be deteriorating due to resource constraints, workforce shortages, or delayed diagnosis. [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eAge-stratified trends revealed a concerning generational shift. The fastest AAMR increases were concentrated among younger and middle-aged adults, particularly those aged 45\u0026ndash;54 (AAPC\u0026thinsp;=\u0026thinsp;+\u0026thinsp;1.94%, 95% CI: +1.21 to +\u0026thinsp;2.68). This shift may be attributed to the rising prevalence of modifiable risk factors such as obesity, diabetes, and hypertension in younger populations, as well as lower rates of screening and awareness. These findings challenge the conventional framing of kidney failure as a disease primarily affecting older adults and emphasize the urgency of integrating CKD screening into routine care for younger age groups. [\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eRacial and ethnic patterns presented a mixed picture. While Non-Hispanic Whites continued to bear the largest absolute burden, their AAMR increased modestly without reaching statistical significance. In contrast, AAMRs among Non-Hispanic Blacks and Hispanics remained stable or slightly declined, possibly reflecting early benefits of targeted interventions and public health efforts in historically underserved communities. However, the disproportionately large increases in absolute deaths among Hispanic and Non-Hispanic Other populations underscore the need for culturally and linguistically tailored outreach, particularly as these groups grow rapidly within the U.S. population. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eSex-based differences remained modest but important. While males maintained higher AAMRs than females, trends over time were largely flat for both sexes, and no statistically significant AAPC was observed. These patterns suggest that sex-based disparities in kidney failure mortality may be less dynamic than other forms of inequity, but nonetheless warrant continued monitoring\u0026mdash;particularly in the context of differential disease awareness, health-seeking behavior, and treatment adherence. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eTaken together, these findings point to an evolving landscape in kidney failure mortality\u0026mdash;one in which the burden is increasingly concentrated among younger adults, urban and Southern populations, and socioeconomically marginalized groups. The stagnation or deterioration of mortality rates in these subgroups highlights the limitations of current population-level strategies and underscores the importance of tailored interventions. Expanding access to early CKD screening, strengthening nephrology capacity in high-risk areas, and integrating community-based prevention initiatives will be essential to reverse these trends. [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eIn sum, the stability of national renal‑failure mortality masks concentrated increases among specific subpopulations and places. A prevention‑to‑treatment strategy\u0026mdash;spanning early risk detection, optimized CKM care, robust post‑AKI follow‑up, and equitable access to advanced therapies\u0026mdash;offers a realistic path to reverse these patterns. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eFuture work should link mortality to longitudinal clinical or claims data to explore patient‑level pathways from CKM risk factors through CKD onset, AKI episodes, and terminal events. Integrating geospatial measures of social deprivation, food and pharmacy access, and environmental stressors would help target interventions. Pragmatic trials and implementation studies in high‑burden communities are essential to translate epidemiologic insight into durable mortality reductions. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eOur analysis has notable strengths: population‑based coverage, long time horizon, standardized age adjustment, and subgroup resolution by region, urbanicity, sex, age, and race/ethnicity. Limitations include potential misclassification in death certificates; lack of granular clinical, behavioral, and environmental covariates; small‑cell suppression affecting county‑level stability; and residual confounding. These constraints mean our estimates should be interpreted as indicators of population burden rather than precise causal effects.\u003c/p\u003e\u003cp\u003eAt the system level, high-burden regions\u0026mdash;particularly the South\u0026mdash;require expanded nephrology capacity, integrated cardio-kidney-metabolic (CKM) care models, and community health worker programs to improve treatment adherence. Equity-focused strategies must address barriers like language access, transportation, and insurance coverage to ensure timely referrals for dialysis education and transplant evaluation. [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eFrom a clinical perspective, the rising mortality among younger adults underscores the need for earlier CKD detection and aggressive CKM risk management in primary care. Key steps include routine eGFR and albuminuria screening for high-risk individuals, tighter control of blood pressure and glycemia, and timely initiation of kidney-protective therapies. Strengthening post-AKI care transitions is also critical to reduce short-term mortality and slow disease progression. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eMethodologically, several extensions could strengthen future work. Beyond Joinpoint models, age\u0026ndash;period\u0026ndash;cohort or negative binomial regressions could separate cohort effects from period shocks. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]State‑ and county‑level mixed‑effects models with social‑determinant covariates (income, educational attainment, insurance expansion, environmental exposures such as extreme heat and air pollution) would help quantify structural contributors. Disaggregating N17, N18, and N19 could clarify whether trends are driven by acute events, chronic progression, or certification ambiguity.\u003c/p\u003e\u003cp\u003eData and methodological considerations must be acknowledged. The COVID-19 pandemic may have perturbed both kidney failure incidence\u0026mdash;through virus-associated AKI and deferred care\u0026mdash;and cause-of-death certification patterns, necessitating cautious interpretation of 2020\u0026ndash;2021 trends[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].Furthermore, variations in death certification across jurisdictions and demographic groups can alter recorded mortality without reflecting true changes in burden, an issue only partially mitigated by multiple-cause mortality data.\u003c/p\u003e\u003cp\u003eKey epidemiological trends reveal critical drivers of kidney failure mortality. The pronounced rise among adults aged 35\u0026ndash;54 suggests a cohort effect of accelerating cardio-kidney-metabolic risk, likely driven by earlier onset of obesity and diabetes, suboptimal risk factor control, and delayed detection. Concurrently, persistent geographic and urban\u0026ndash;rural disparities align with established gradients in comorbidities and healthcare access, though the declining trend in the Northeast demonstrates the potential of integrated chronic disease management to curb mortality [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis nationwide analysis reveals that kidney failure mortality remains a significant and unequal public health burden in the United States. Rising risks among younger adults, metropolitan populations, and Southern residents demand urgent, tailored interventions. Policies must be guided by disaggregated data and committed to advancing health equity in kidney care.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthical approval\u003c/p\u003e\n\u003cp\u003eNo ethical approval was required for this study design, as all data were obtained from publicly available sources.\u003c/p\u003e\n\u003cp\u003eConsent\u003c/p\u003e\n\u003cp\u003eInformed consent was not required as we utilized data from a de-identified government-provided public use dataset.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003eAuthor contribution\u003c/p\u003e\n\u003cp\u003eYong Ding: Contributed equally to the conception, design of the study, data collection and drafting of the manuscript. Chang Chen, Bingjie Yang, Kangkang Ding: Participated in data analysis and manuscript revision.He Wang (corresponding author): Supervised the entire study, revised the manuscript critically, and approved the final version for publication.\u003c/p\u003e\n\u003cp\u003eConflict of Interest\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eData availability statement\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are openly available in CDC Wonder at [https://wonder.cdc.gov/].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLevin A, Ahmed SB, Carrero JJ, et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int. 2024 Apr;105(4):684-701. PMID: 38519239.\u003c/li\u003e\n\u003cli\u003eJohansen KL, Chertow GM, Foley RN, et al. US Renal Data System 2020 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2021 Apr;77(4 Suppl 1):A7-A8. PMID: 33752804; PMCID: PMC8148988.\u003c/li\u003e\n\u003cli\u003eBello AK, Okpechi IG, Osman MA, et al. Epidemiology of haemodialysis outcomes. Nat Rev Nephrol. 2022 Jun;18(6):378-395. PMID: 35194215; PMCID: PMC8862002.\u003c/li\u003e\n\u003cli\u003eStewart F, Kistler K, Du Y, Singh RR, Dean BB, Kong SX. Exploring kidney dialysis costs in the United States: a scoping review. J Med Econ. 2024;27(1):618-625. PMID: 38605648.\u003c/li\u003e\n\u003cli\u003eNorton JM, Moxey-Mims MM, Eggers PW, Narva AS, Star RA, Kimmel PL, Rodgers GP. Social Determinants of Racial Disparities in CKD. J Am Soc Nephrol. 2016 Sep;27(9):2576-2595. PMID: 27178804; PMCID: PMC5004663.\u003c/li\u003e\n\u003cli\u003eMokdad AH, Dwyer-Lindgren L, Bertozzi-Villa A, et al. Trends and patterns of disparities in diabetes and chronic kidney disease mortality among US counties, 1980\u0026ndash;2014. Popul Health Metr. 2022 Feb 22;20(1):9. PMID: 35193593; PMCID: PMC8862531.\u003c/li\u003e\n\u003cli\u003eTiwari, C., K. Beyer, and G. Rushton, The impact of data suppression on local mortality rates: the case of CDC WONDER. Am J Public Health, 2014. 104(8): p. 1386-8.\u003c/li\u003e\n\u003cli\u003eRashid AM, Zhao X, Li X, et al. Trends in mortality related to kidney failure and diabetes mellitus in the United States: a 1999\u0026ndash;2020 analysis. Endocrinol Diabetes Metab. 2024;7(4):e493. PMID: 38916852; PMCID: PMC11519297.\u003c/li\u003e\n\u003cli\u003eChen Z, Fu X, Wang J, et al. Kidney failure-related excess mortality during the first three years of the pandemic in the United States. BMC Public Health. 2025;25:21422. PMCID: PMC11745008.\u003c/li\u003e\n\u003cli\u003eIngram DD, Franco SJ. 2013 NCHS Urban\u0026ndash;Rural Classification Scheme for Counties. Vital Health Stat 2. 2014;(166):1\u0026ndash;73. PMID: 24776070.\u003c/li\u003e\n\u003cli\u003eIngram DD, Franco SJ. 2006 NCHS Urban\u0026ndash;Rural Classification Scheme for Counties. Vital Health Stat 2. 2012;(154):1\u0026ndash;65. PMID: 22783637.\u003c/li\u003e\n\u003cli\u003eCross SH, Kaufman BG, Warraich HJ, Taylor DH Jr. Trends in place of death for individuals with advanced kidney disease in the United States, 2003\u0026ndash;2017. J Pain Symptom Manage. 2021;61(1):36\u0026ndash;44. PMID: 32791183.\u003c/li\u003e\n\u003cli\u003eAnderson RN, Rosenberg HM. Age standardization of death rates: implementation of the year 2000 standard. Natl Vital Stat Rep. 1998;47(3):1\u0026ndash;16, 20. PMID: 9796247.\u003c/li\u003e\n\u003cli\u003eKim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19(3):335\u0026ndash;351. PMID: 10649300.\u003c/li\u003e\n\u003cli\u003eKim HJ, Howlader N, Enewold L, et al. Twenty years since Joinpoint 1.0: two major extensions of the model. Cancer Res Stat Treat. 2022;5(3):463\u0026ndash;472. PMID: 35522060.\u003c/li\u003e\n\u003cli\u003eClegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK. Estimating average annual percent change in trend analysis. Stat Med. 2009;28(29):3670\u0026ndash;3682. PMID: 19856324.\u003c/li\u003e\n\u003cli\u003eSnow KK, Patzer RE, Patel SA, et al. County-Level Characteristics Associated With Variation in End-Stage Kidney Disease Mortality in the United States, 2010\u0026ndash;2018. Kidney360. 2022;3(9):1554\u0026ndash;1565. PMID: 36128479; PMCID: PMC9438422.\u003c/li\u003e\n\u003cli\u003eMokdad AH, Dwyer-Lindgren L, Bertozzi-Villa A, et al. Trends and patterns of disparities in diabetes and chronic kidney disease mortality among US counties, 1980\u0026ndash;2014. Popul Health Metr. 2022;20(1):9. PMID: 35193593; PMCID: PMC8862531.\u003c/li\u003e\n\u003cli\u003eDwyer-Lindgren L, Bertozzi-Villa A, Stubbs RW, et al. US County-Level Trends in Mortality Rates for Major Causes of Death, 1980\u0026ndash;2014. JAMA. 2016;316(22):2385\u0026ndash;2401. PMID: 27959996; PMCID: PMC5576343.\u003c/li\u003e\n\u003cli\u003eRaja A, Raja S, Amin SB, et al. Temporal trends in hypertension-related end-stage renal disease mortality rates: analysis by gender, race/ethnicity, and census region in the United States, 1999\u0026ndash;2020. Front Nephrol. 2024;3:1339312. PMID: 38288382.\u003c/li\u003e\n\u003cli\u003eGrobman B, Azeem B, Khan A, et al. Trends and Disparities in Deaths from Kidney Disease Among Older Adults in the United States. J Clin Med. 2025;14(14):4950. PMID: 40725643; PMCID: PMC12295388.\u003c/li\u003e\n\u003cli\u003eXu F, Stewart AJ, Khanam MA, Decloedt EH, Al ence S, Qayed E, et al. Urban\u0026ndash;rural differences in acute kidney injury mortality in the United States. Am J Prev Med. 2025. PMID: 39179183.\u003c/li\u003e\n\u003cli\u003eEllison-Barnes A, Johnson S, Gudzune KA. Trends in Obesity Prevalence Among Adults Aged 18 Through 25 Years, 1976\u0026ndash;2018. JAMA. 2021;326(20):2073\u0026ndash;2074. PMID: 34812876.\u003c/li\u003e\n\u003cli\u003eHardy ST, Hardy RJ, Harrell FE Jr, et al. Trends in Blood Pressure Control Among US Adults, 1999\u0026ndash;2020. JAMA. 2024. PMID: 38254218.\u003c/li\u003e\n\u003cli\u003eTang O, Vaidya A, Kline A, et al. Hypertension Awareness, Treatment, and Control Among Young Adults in the United States, 2011\u0026ndash;2020. Hypertension. 2024. PMID: 40156902.\u003c/li\u003e\n\u003cli\u003eNdumele CE, Rangaswami J, Chow SL, et al.; American Heart Association. Cardiovascular\u0026ndash;Kidney\u0026ndash;Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023;148(20):1606\u0026ndash;1635. PMID: 37807924.\u003c/li\u003e\n\u003cli\u003eVictor RG, Lynch K, Li N, et al. A Cluster-Randomized Trial of Blood-Pressure Reduction in Black Barbershops. N Engl J Med. 2018;378(14):1296\u0026ndash;1308. PMID: 29527973.\u003c/li\u003e\n\u003cli\u003eIslam NS, Wyatt LC, Kwon SC, et al. Integrating Community Health Workers Into Community-Based Primary Care Practice Settings to Improve Blood Pressure Control Among South Asian Immigrants in New York City: Results From a Randomized Control Trial. Circ Cardiovasc Qual Outcomes. 2023;16(3):e009321. PMID: 36815464.\u003c/li\u003e\n\u003cli\u003eHeerspink HJL, Stef\u0026aacute;nsson BV, Correa-Rotter R, et al.; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436\u0026ndash;1446. PMID: 32970396.\u003c/li\u003e\n\u003cli\u003eHerrington WG, Staplin N, Judge PK, et al.; EMPA-KIDNEY Collaborative Group. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023. PMID: 36331190.\u003c/li\u003e\n\u003cli\u003eHirsch JS, Ng JH, Ross DW, et al.; Northwell COVID-19 Research Consortium. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020. PMID: 32416116.\u003c/li\u003e\n\u003cli\u003eChan L, Chaudhary K, Saha A, et al. AKI in Hospitalized Patients with COVID-19. J Am Soc Nephrol. 2021;32(1):151\u0026ndash;160. PMID: 32883700.\u003c/li\u003e\n\u003cli\u003eMieno MN, Tanaka N, Arai T, et al. Accuracy of Death Certificates and Assessment of Factors for Misclassification of Underlying Cause of Death. J Epidemiol. 2016;26(4):191\u0026ndash;198. PMID: 26639750.\u003c/li\u003e\n\u003cli\u003eHarel Z, Wald R, Bargman JM, et al. Nephrologist Follow-up Improves All-Cause Mortality of Patients With Severe Acute Kidney Injury. Kidney Int. 2013;83(5):901\u0026ndash;908. PMID: 23325077.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pubh","sideBox":"Learn more about [BMC Public Health](http://bmcpublichealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pubh/default.aspx","title":"BMC Public Health","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"renal failure, epidemiology, mortality, racial disparity, sex disparity, trends","lastPublishedDoi":"10.21203/rs.3.rs-8074626/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8074626/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eRenal failure (RF) is a systemic disease and one of the leading causes of non-communicable disease mortality worldwide. Its high treatment costs, resource reliance, and social impact impose a significant burden on global health systems. This study analyzes CDC WONDER data on deaths related to RF (ICD-10, N17-N19) among adults in the United States from 1999 to 2023. Age-adjusted mortality rates (AAMR) and annual percent change (APC) were calculated by year, sex, age group, race/ethnicity, geographic region, and urbanization status. A total of 1,138,750 kidney failure\u0026ndash;related deaths were recorded between 1999 and 2023. The South had the highest cumulative deaths and the fastest-growing AAMR (AAPC\u0026thinsp;=\u0026thinsp;+\u0026thinsp;0.7605), while the Northeast was the only region with a declining trend (AAPC = \u0026minus;\u0026thinsp;0.5704). Females showed consistently higher AAMRs than males, with both sexes exhibiting slight upward trends. Non-Hispanic Whites had the highest mortality burden and a rising AAMR, while Non-Hispanic Blacks and Hispanics showed modest declines. Younger adults (ages 25\u0026ndash;54) experienced the fastest increase in AAMR, particularly those aged 45\u0026ndash;54 (AAPC\u0026thinsp;=\u0026thinsp;+\u0026thinsp;1.94). Urban residents faced a rising burden, whereas rural areas experienced slight improvements. Overall, the data indicate a steady increase in RF-related mortality, with more substantial increases observed in certain regions and populations. The trend in AAMR also shows a slight upward trajectory, suggesting an increasing burden of renal failure among specific demographics and areas. This underscores the necessity for targeted and equitable intervention strategies.\u003c/p\u003e","manuscriptTitle":"Trends in Renal Failure-Related Mortality among Adults in the America: A National Cross-Sectional Analysis (CDC Database Study 1999–2023)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-27 12:36:13","doi":"10.21203/rs.3.rs-8074626/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-22T06:08:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-20T20:15:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-19T05:43:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313564405565917425751342826888148711341","date":"2025-12-19T05:21:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"255595747260778289173501070009678039735","date":"2025-12-13T11:23:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221675556480443828120514555701121569877","date":"2025-11-26T23:14:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"233866465788487061861861960915365101304","date":"2025-11-25T04:24:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"12416553017005178356734685698302760867","date":"2025-11-24T18:24:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"157741789928245373966788474452786582138","date":"2025-11-21T16:16:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-20T05:57:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"261374573279673878643771321704602934992","date":"2025-11-20T05:41:19+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-19T16:14:51+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-11T10:48:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-11T08:36:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-11T08:34:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Public Health","date":"2025-11-10T08:29:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pubh","sideBox":"Learn more about [BMC Public Health](http://bmcpublichealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pubh/default.aspx","title":"BMC Public Health","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cc82ab65-19b3-41f7-8d7c-944121703b06","owner":[],"postedDate":"November 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:06:14+00:00","versionOfRecord":{"articleIdentity":"rs-8074626","link":"https://doi.org/10.1186/s12889-026-26276-w","journal":{"identity":"bmc-public-health","isVorOnly":false,"title":"BMC Public Health"},"publishedOn":"2026-01-23 15:57:53","publishedOnDateReadable":"January 23rd, 2026"},"versionCreatedAt":"2025-11-27 12:36:13","video":"","vorDoi":"10.1186/s12889-026-26276-w","vorDoiUrl":"https://doi.org/10.1186/s12889-026-26276-w","workflowStages":[]},"version":"v1","identity":"rs-8074626","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8074626","identity":"rs-8074626","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}