Trends and Disparities in Chronic Kidney Disease and Hypertension-Related Mortality in the United States, 2000–2023

Trends and Disparities in Chronic Kidney Disease and Hypertension-Related Mortality in the United States, 2000–2023 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Trends and Disparities in Chronic Kidney Disease and Hypertension-Related Mortality in the United States, 2000–2023 Mohid Zulfiqar, Syed Ahmed Ali shah, Asim Sajjad, Ammad Uddin, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8880840/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Chronic kidney disease (CKD) and hypertension (HTN) are closely linked, often coexisting to increase cardiovascular risk and mortality. Despite their growing burden, long-term national mortality patterns remain insufficiently characterized. Objective Our objective is to evaluate temporal trends and disparities in CKD and HTN-related mortality in the United States from 2000 to 2023. Methods We obtained mortality data from the CDC WONDER Multiple Cause-of-Death database using ICD-10 codes for CKD and HTN. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated by sex, race/ethnicity, and state. Joinpoint regression identified inflection points and annual percent change (APC) in mortality. Results Between 2000 and 2023, 1,618,000 CKD and HTN-related deaths were recorded in the United States. Overall AAMRs increased from 4.3 to 7.3 per 100,000, with four distinct phases: decline (2000–2005), plateau (2005–2012), sharp rise (2012–2019), and continued escalation during the COVID-19 era (2019–2023). Men consistently had higher AAMRs than women, and non-Hispanic Black individuals showed the greatest racial disparities. Geographic variation was marked, with Southern states recording the highest rates, while states such as Mississippi and Louisiana reported mortality more than double that of Colorado and Massachusetts. Conclusion CKD and HTN-related mortality in the U.S. has risen substantially since 2012, with widening sex, racial, and geographic disparities. Targeted prevention, equitable access to CKD and blood pressure management, and improved health system resilience are urgently needed. Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Over the past few decades, Hypertension (HTN) has emerged as one of the most serious global health issues, often said to be the “silent killer.” It affects approximately 1.28 billion adults aged 30 to 79 years, and among these people, more than two-thirds are in low and middle-income countries 1 . HTN is said to be the number one cause of cardiovascular disease and premature death in the world, significantly increasing the risk of stroke, heart attack, and heart failure 2 . Even with modern treatments available, only 54% of adults with HTN are diagnosed, while only 42% are treated, and only 21% reach adequate control of this condition. 3 . Along with the rising incidence of HTN, the increased recognition of chronic kidney disease (CKD) as a major contributor to cardiovascular morbidity and mortality is also a cause of significant concern. CKD is estimated to affect 850 million people globally and is expected to see a substantial increase, as projections estimate that it will become the fifth leading cause of years of life lost by 2040 4,5 . Additionally, Hypertension is one of the leading causes of CKD and often, in turn, complicates reduced kidney function 6 . Epidemiologic studies have reported that hypertension accounts for nearly one-third of CKD globally, while CKD itself worsens blood pressure control through the activation of the renin-angiotensin-aldosterone system, causing sympathetic overactivity, and faulty sodium transport 7 , 8 . Despite strong evidence linking HTN to CKD, major gaps remain regarding national patterns and temporal trends of this comorbidity. CKD with HTN increases the risks of cardiovascular disease, stroke, heart failure, and premature mortality. 9 while poorly managed cases contribute to the increasing global healthcare burden. This study aims to addresses these gaps by examining trends and disparities in HTN among CKD patients in the United States (2000–2023) using CDC WONDER mortality data as well as asses disparities in mortalities of different demographic, sex, racial/ethnic, and regional differences, with particular attention to excess mortality during the COVID-19 pandemic given the heightened vulnerability of this population to healthcare disruption 10 . METHODS Study setting and population We analysed mortality data related to CKD and HTN obtained from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Database 11 . CDC-WONDER is a comprehensive database that contains death certificate data from all fifty states and the District of Columbia. We used the Multiple Cause of Death Public Use Record to extract data about patients who died with both CKD and HTN as either an underlying cause or contributing cause of death in the United States from 2000 to 2023. We collected death records for patients aged 25 and older using the following International Classification of Diseases, 10th Revision, Clinical Modification codes N18 for CKD and I10-I15 for HTN. Other researchers have used these same codes to identify CKD and HTN in administrative databases 12 , 13 . Additionally, we followed the guidelines established by the reporting standards of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 14 .Our study did not require approval from the local institutional review board because it used an anonymous public data set provided by the government of the United States. Data extraction The extracted data included population, year, and demographics such as sex, race/ethnicity, age, and regional details. Race/ ethnicity was classified into the following categories: Hispanic or Latino, Non-Hispanic (NH) Black or African American, NH White, and NH Asian or Pacific Islander. The Urban–Rural classification was based on the National Center for Health Statistics Urban–Rural Classification Scheme. The population was divided into urban (large metropolitan area, medium/ small metropolitan area) and rural (population < 50,000) CKD and HTN-related mortality counties according to the 2013 U.S. census classification 15 . Regions were classified as Northeast, Midwest, South, and West based on U.S. Census Bureau definitions 16 . Statistical analysis The crude and age-adjusted mortality rates (CMRs and AAMRs) per 100,000 individuals from 2000 to 2023 were calculated to analyse the trends in mortality related to CKD and HTN. CMRs were calculated by dividing the deaths related to CKD and HTN by the total U.S. population each year. AAMRs were calculated by standardizing CKD and HTN-related deaths to the 2000 U.S. population, with 95% confidence intervals 17 . The AAMRs were used to analyse mortality patterns across various demographic classifications. The trends in AAMR were determined using the Joinpoint Regression Program (Joinpoint Version 5.1.0, National Cancer Institute) that reported annual percentage change (APC) along with 95% CI 18 . Significant changes in AAMR over time were assessed using log-linear regression models to examine temporal variations. APCs were considered to increase or decrease if the slope representing the change in mortality significantly deviated from zero, as determined by 2-tailed t-tests. A P-value of less than 0.05 indicated statistical significance. RESULTS CKD and HTN caused 222,136 deaths between 2000 and 2023. Most of these deaths (42.3%) occurred in medical facilities, followed by deaths at the nursing homes or long-term care facilities (28.2%), descendants homes (25.7%), and hospice facilities (3.8%). (Supplementary Table 1, Supplementary Table 2). Annual trends for CKD and HTN-related AAMR The overall AAMR increased from 2000 to 2009 (APC = 0.6, 95% CI: -4.4 to 5.7). From 2009 to 2012, AAMR increased steeply (APC = 50.4, 95% CI: -7.8 to 145.6), then it decreased drastically till 2015 (APC = -69.0, 95% CI: -90.2 to -1.3). Finally, AAMR increased sharply till 2023 (APC = 29.5, 95% CI: 14.9 to 46.1). ( Fig. 1 ) CKD and HTN-related AAMR stratified by sex Throughout the study period from 2000 to 2023, the AAMR was consistently higher for men than for women. Specifically, the overall AAMRs were 5.3 for men and 3.8 for women. In men, the AAMR increased from 2000 to 2009 (APC = 0.4, 95% CI: -2.8 to 3.6). From 2009 to 2012, AAMR increased steeply (APC = 51.0, 95% CI: 14.5 to 99.2), then it decreased drastically till 2015 (APC = -69.0, 95% CI: -84.4 to -38.4). Finally, AAMR increased sharply till 2023 (APC = 30.3, 95% CI: 18.6 to 43.3). Females displayed analogous trajectories, with the AAMR decreasing slightly from 2000 to 2009 (APC = -0.4, 95% CI: -6.1 to 5.6). From 2009 to 2012, AAMR increased steeply (APC = 54.4, 95% CI: -7.1 to 156.6), then it decreased drastically till 2015 (APC = -68.0, 95% CI: -91.4 to 18.2). Finally, AAMR increased sharply till 2023 (APC = 26.7, 95% CI: 11.2 to 44.4) ( Fig. 1 , Supplementary Table 4) CKD and HTN-related AAMR stratified by race NH Black or African Americans had the highest overall AAMR among all the ethnicities throughout the study period, with an AAMR of 10.0. Meanwhile, the Hispanic or Latino, NH Asian or Pacific Islander and NH White populations had AAMRs of 5.0, 4.3 and 3.6, respectively. The trends in AAMR for NH Black or African American saw a dip from 2000 to 2009 (APC = -2.8, 95% CI: -7.7 to 2.5). From 2009 to 2012, AAMR increased steeply (APC = 58.6, 95% CI: -3.9 to 161.8), then it decreased drastically till 2015 (APC = -69.4, 95% CI: -90.5 to -1.2). Finally, AAMR increased sharply till 2023 (APC = 18.7, 95% CI: 3.8 to 35.8). Similarly, NH Asian or Pacific Islander and Hispanic or Latino exhibited resembling AAMR trends. For NH Whites, the initial phase from 2000 to 2009 showed a slight increase in AAMR (APC = 15.3, 95% CI: 13.6 to 18.2) unlike other races where they showed a dip in AAMR during this period. This was followed by a sharper rise extending to 2012 (APC = 46.8, 95% CI: -10.6 to 141.1). Then AAMR decreased drastically till 2015 (APC = -67.7, 95% CI: -90.3 to 7.7). Finally, AAMR increased sharply till 2023 (APC = 29.8, 95% CI: 14.9 to 46.7). ( Fig. 2 , Supplementary Table 5) CKD and HTN-related AAMR stratified by geographic regions Our analysis revealed stark disparities in the geographic locations of deaths. In terms of urbanization from 2000 to 2020, nonmetropolitan areas exhibited a higher AAMR (5.1) than metropolitan (4.7). The trends for non-metropolitan areas can be divided into four segments. The trend in AAMR increased from 2000 to 2009 (APC = 1.8, 95% CI: -0.7 to 4.3). From 2009 to 2012, AAMR increased steeply (APC = 42.7, 95% CI: 15.8 to 75.8), then it decreased drastically till 2015 (APC = -68.2, 95% CI: -83.3 to -39.7). Finally, AAMR increased sharply till 2023 (APC = 36.0, 95% CI: 23.0 to 50.4). Similarly, metropolitan areas showed parallel trends in AAMR, with a decrease from 2000–2009 (APC of -0.14, 95% CI: -2.6 to 2.4). Subsequently, from 2009 to 2012, AAMR increased steeply (APC = 56.7, 95% CI: 23.2 to 99.3), then it decreased drastically till 2015 (APC = -72.1, 95% CI: -85.9 to -45.0). Finally, AAMR increased sharply till 2023 (APC = 36.7, 95% CI: 22.4 to 52.7) (Supplementary Fig. 2, Supplementary Table 6). In regard to census region from 2000 to 2023, the West region exhibited the highest overall AAMR at 4.8, followed by the Midwest with an overall AAMR of 4.6, the South at 4.5, and the Northeast at 3.3. The Northeast saw a decrease in AAMR from 2000 to 2009 (APC = -0.5, 95% CI: -3.3 to 2.3.). From 2009 to 2012, AAMR increased steeply (APC = 55.3, 95% CI: 19.9 to 101.3), then it decreased drastically till 2015 (APC = -69.0, 95% CI: -84.2 to -39.1). Finally, AAMR increased sharply till 2023 (APC = 26.2, 95% CI: 15.4 to 38.0). The South region showed similar trends. The Midwest saw a slight increase in AAMR from 2000 to 2009 (APC = 0.9, 95% CI: -2.6 to 4.5). From 2009 to 2012, AAMR increased steeply (APC = 45.7, 95% CI :6.0 to 100.4), then it decreased drastically till 2015 (APC = -68.1, 95% CI: -86.9 to -22.1). Finally, AAMR increased sharply till 2023 (APC = 30.5, 95% CI: 17.6 to 44.8). The West exhibited a similar trend. ( Fig. 4 , Supplementary Table 8). States exhibited significant differences in AAMR, with values ranging from 1.9 in Nevada to 8.1 in North Dakota. States in the upper 90th percentile of AAMRs for CKD-HTN patients included North Dakota, the District of Columbia, Ohio, West Virginia, and Oklahoma. These states had AAMRs that were nearly three times higher than those in the lower 10th percentile, which included Nevada, Utah, Connecticut, Wyoming, and Massachusetts. ( Fig. 3 , Supplementary Table 7). CKD and HTN-related AAMR stratified by age Throughout the study period from 2000 to 2023, the overall AAMR was highest in 65–85 + age group, at 19.4, followed by the 45–64 age group with AAMR of 1.4, while the 25–44 age group had the lowest overall AAMR, 0.2. For the 65–85 + age group, AAMR increased from 2000 to 2009 (APC = 0.6, 95% CI: -5.1 to 6.5). From 2009 to 2012, AAMR increased steeply (APC = 49.5, 95% CI: -9.8 to 147.9), then it decreased drastically till 2015 (APC = -66.4, 95% CI: -91.1 to -27.2). Finally, AAMR increased sharply till 2023 (APC = 19.5, 95% CI: 3.8 to 37.5). For the 45–64 age group, the trend was similar to the 65–85 + age group. The 25–44 age group showed a steep decrease from 2000 to 2008 (APC = -5.7, 95% CI: -15.8 to 5.7), followed by a steeper increase till 2012 (APC = 61.2, 95% CI: 16.9 to 122.4), then it decreased drastically till 2015 (APC = -67.1, 95% CI: -97.2 to 287.6). Finally, AAMR increased sharply till 2023 (APC = 23.9, 95% CI: 1.2 to 51.6). (Supplementary Fig. 1, Supplementary Table 3, Supplementary Table 9). DISCUSSION Our study analyzed 24 years (2000–2023) of trends in CKD and HTN-related mortality in U.S. adults using the CDC WONDER database. We found several disparities in mortalities among different demographics. First of all, we observed that the overall mortality displayed a fluctuating pattern with four distinct phases. A gradual increase from 2000 to 2009, this was followed by a steep rise from 2009 to 2012, and then a drastic decline from 2012 to 2015, and finally an increase from 2015 to 2023. Secondly, upon stratifying the data based on gender, our analysis revealed that men had consistently higher mortality rates compared to women. Thirdly, we observed substantial racial disparities, with NH Black or African Americans exhibiting the highest mortality rates among all ethnicities, while NH Whites had the lowest AAMR. Fourthly, geographic disparity was also observed, with non-metropolitan areas exhibiting higher AAMR relative to metropolitan areas. Finally, our analysis demonstrated significant state-based differences in mortality, with North Dakota showing the highest AAMR and Nevada showing the lowest values, representing nearly a three-fold difference between states in the upper and lower percentiles. (Table 1) We found that the pattern of mortality observed in our study is characterized by fluctuating trends rather than a consistent decline, which we think is evidence of the complex nature of CKD and HTN-related mortality over the past two decades. The initial gradual increase from 2000 to 2009 may in part be due to the growing prevalence of diabetes, obesity, and metabolic syndrome, which are major risk factors for both CKD and hypertension 19 , 20 . The steep rise in mortality from 2009 to 2012 coincides with the aftermath of the 2008 financial crisis, which may have limited healthcare access and delayed preventive care, adversely affecting patients with chronic conditions requiring continuous management 21 , 22 , 12 . The steep decline observed from 2012 to 2015 aligns with the implementation of healthcare reforms, including expanded insurance coverage through the Affordable Care Act, which improved access to nephrology care and antihypertensive medications 23 , 24 , 25 , 12 . Additionally, this period of time also saw significant improvements in CKD management guidelines, such as improved blood pressure targets and the introduction of novel therapeutic approaches such as SGLT2 inhibitors and GLP-1 receptor agonists 26 , 27 . The increase in mortality from 2015 to 2023 with peak during the COVID-19 pandemic, may be due to several factors, including systemic healthcare disruption during Covid or it may be explained by the aging population of united states as well as the increasing prevalence of comorbidities along with lack of adherence to medication, all these factors compounded the disruptive effects on healthcare during covid and disproportionately affected patients with CKD and hypertension 28 , 29 . Regarding Sex, men consistently exhibited higher CKD and HTN-related mortality rates compared to women. This can be attributed to several factors, such as biological and behavioral factors. Men demonstrate more aggressive progression of both CKD and HTN, with studies showing faster decline in estimated glomerular filtration rate and higher adverse cardiovascular event rates 30 , 31 . The higher prevalence of poorly controlled hypertension in men, which is compounded by reduced adherence to medication as well as delayed healthcare-seeking behavior among men, contributes significantly to adverse outcomes observed among men 32 , 33 . Studies show that men exhibit higher baseline RAAS activation, with elevated angiotensin II and aldosterone levels, which causes increased vasoconstriction and sodium retention 34 . This contributes to poorer blood pressure control and faster CKD progression in men. Additionally, men respond less effectively to ACE inhibitors and ARBs, often requiring more intensive therapy 35 . As a result, poor hypertension management drives greater cardiovascular mortality in men with CKD 36 . The protective effects of estrogen in premenopausal women, including vasodilation and anti-inflammatory properties as well as cardioprotective mechanisms, contrast with the potentially negative impact of testosterone on vascular health and kidney function in men 36 , 37 . Men also exhibit higher rates of modifiable risk factors that worsen both CKD and hypertension, including smoking, excessive alcohol consumption, obesity, and diabetes, while also being less likely to engage in preventive healthcare measures 38 , 39 . We observed substantial racial and ethnic disparities in CKD and HTN-related mortality rates, with NH Black or African Americans demonstrating the highest AAMR among all groups. We also observed that NH White Americans showed the lowest rates. These disparities might in part be due to different genetic vulnerability to hypertensive nephropathy and CKD progression among NH Blacks, as African Americans exhibit a higher prevalence of APOL1 gene variants, which are associated with increased kidney disease risk and faster progression to end-stage renal disease 40 , 41 . Additionally, structural racism within healthcare systems may also lead to delayed nephrology referrals, worsen blood pressure management, and reduced access to specialized CKD care among minority populations 42 , 43 . Cultural factors such as dietary patterns high in sodium and processed foods, as well as traditional mistrust of healthcare institutions, may further worsen disease management and adherence to medication 44 , 45 . The ongoing wealth gap and residential segregation experienced by African Americans often result in exposure to environmental stressors such as air pollution, food deserts, and neighborhood violence, which are independently linked with accelerated kidney disease progression and cardiovascular mortality 46 , 47 . Furthermore, the differences in coverage of insurance and lack of access to pharmacy may also limit the availability of newer, more effective antihypertensive medications and nephroprotective therapies in minority communities 48 , 49 . We also observed that Hispanic or Latino and NH Asian or Pacific Islander populations showed intermediate mortality rates, which may be due to heterogeneity within these broader ethnic categories and differences in acculturation, healthcare access, as well as socioeconomic integration 50 , 51 . Our analysis revealed significant geographic disparities in CKD and HTN-related mortality, with non-metropolitan areas exhibiting higher AAMR compared to metropolitan areas. These disparities may in part be because of exposures to nephrotoxic environmental factors, including agricultural pesticides, heavy metals from mining activities, as well as contaminated groundwater, all of which directly damage kidney function and contribute to making hypertension even more prevalent in rural communities 52 , 53 . Additionally, rural areas face healthcare infrastructure challenges, such as fewer nephrologists per capita, longer travel distances to get specialized care, and reduced availability of dialysis facilities. All these factors may contribute to delayed diagnosis and may lead to more adverse effects of the disease 54 . The composition of rural populations' demographics, which are mostly older age people with higher prevalence of diabetes and obesity, and dietary patterns which are characterized by limited access to fresh foods and a reliance on high-sodium processed items, can contribute to the risks for kidney disease and poor blood pressure control 55 , 56 . Among U.S. regions, the West exhibited the highest overall AAMR, which may be due to mining-related environmental exposures and water scarcity issues, while we also observed that the Northeast showed the lowest rates. This may be due to stronger healthcare infrastructure and lower toxin exposure in this region 57 . State-level variations in mortality were also observed, with North Dakota showing more than fourfold higher mortality rates than Nevada. This means that Differences in CKD and Hypertension mortality by state are signals of upstream factors, which may include healthcare policy such as Medicaid expansion, occupational exposures (e.g. in oil, mining, or agriculture), and population-specific risks emanating from poverty, educational attainment, and structural racism. These architectural determinants must interact with downstream clinical factors to engender geographic bias in disease outcomes. 58 Although mortality rates related to chronic kidney disease (CKD) and hypertension (HTN) have declined gradually over the years in the United States, the global prevalence of CKD still remains a significant cause of concern, as it is reported that CKD attributed to hypertension globally has more than doubled, rising from 11 million cases in 1990 to over 24 million in 2021 59 . Considering this, maintaining the downward trend in CKD- and HTN-related mortality requires an active approach. First, early detection as well as early intervention should be given the utmost priority, this can be done by adding routine renal function assessments, such as urine sediment analysis and renal ultrasonography, into the standard care of all hypertensive patients. This approach may enable the identification of chronic kidney disease (CKD) at an earlier time, at a potentially reversible or manageable stage in the disease 60 . Second, lifestyle and dietary interventions also play a key role in blood pressure control. One great option is the Stop Hypertension (DASH) diet, which prescribes fruits, vegetables, low-fat dairy, and whole grains incorporation into the diet. Most importantly, reducing sodium intake below guideline levels has been shown to independently lower blood pressure. When these strategies are combined, they can lead to a greater reduction in hypertension risk 61 . Third, adequate management of medication should also be given priority, especially in elderly patients, specifically minimizing harmful polypharmacy in patients of this demographic, as well as appropriately treating coexisting conditions such as hypertension. Finally, healthcare systems in high-burden and underserved regions must be strengthened. This includes increased investment in renal care infrastructure and expanded training for primary care providers to improve access to early diagnosis, dialysis, and long-term CKD management 60 . Our study should be interpreted considering several limitations. The accuracy of the CDC WONDER dataset relies heavily on the precision of death certificate reporting, particularly regarding the underlying and contributing causes of mortality. Given that the cause of death often has many factors, this may result in misclassification or underreporting of CKD, and HTN may occur. Additionally, the dataset includes only basic demographic information, such as age, sex, race/ethnicity, geographic region, and urbanization status, while lacking detailed clinical data, including co-morbidities, socioeconomic status, medication history, and access to healthcare. This absence of clinical context limits the ability to adjust for potential confounding factors. Furthermore, the reliance on death certificate data, rather than full medical records, may result in underreporting of CKD or HTN diagnoses, especially if they were not explicitly listed as a cause or contributing factor of death. Consequently, the true burden of CKD and HTN-related mortality may be underestimated in the United States. Finally, due to the limitations of the available data, it was not possible to stratify individuals based on disease severity or progression using clinical tools such as estimated glomerular filtration rate (eGFR) for CKD or blood pressure staging for HTN. 12 CONCLUSION This study delineates key trends and disparities in CKD- and hypertension-related mortality in the United States from 2000 to 2023. Mortality trajectories were influenced by socioeconomic changes, healthcare reforms, and the COVID-19 pandemic. Elevated mortality persisted among men and non-Hispanic Black populations, with disproportionate burdens also observed in rural and select state-level populations. These findings emphasize the imperative for early detection, equitable healthcare access, and targeted interventions. Sustained progress will require strengthening healthcare infrastructure, addressing social determinants of health, and expanding preventive strategies. Future research should integrate clinical and socioeconomic datasets to inform more precise, population-specific health policies. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests All authors declare no competing interests. Funding The authors received no funds, grants, or financial support for this study. Author Contribution Mohid Zulfiqar – Conceptualization, study design, data extraction from CDC WONDER, manuscript drafting, and critical revisions.Syed Ahmed Ali Shah – Study design, data extraction from CDC WONDER, literature review, and manuscript drafting.Asim Sajjad – Data extraction from CDC WONDER, preliminary data analysis, and quality checks.Ammad Uddin – Data management, literature review, and manuscript editing.Abbeha Talib – Data extraction from CDC WONDER, organization of study materials, and manuscript proofreading.Hassan Abdul Aziz Dhedhi – Statistical analysis, interpretation of results, and manuscript editing.Muhammad Shafay Aamir – Data validation, statistical analysis, and manuscript preparation.Hermann Yokolo – Study supervision, methodology guidance, and critical review .Muhammad Khalid Afridi – Interpretation of results, drafting of findings, and final manuscript revisions. Acknowledgements Not applicable. Data Availability The data supporting the findings of this study were obtained from the CDC WONDER online database (Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research). The datasets used and analyzed during the current study are publicly available and can be accessed at https://wonder.cdc.gov Clinical trial number Not applicable. References Hypertension. Accessed September 16, 2025. https://www.who.int/news-room/fact-sheets/detail/hypertension Abbafati C, Abbas KM, Abbasi-Kangevari M, et al. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet . 2020;396(10258):1223-1249. doi:10.1016/S0140-6736(20)30752-2 Mills KT, Bundy JD, Kelly TN, et al. Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-based Studies from 90 Countries. 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Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science . 2010;329(5993):841-845. doi:10.1126/SCIENCE.1193032 Kopp JB, Nelson GW, Sampath K, et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol . 2011;22(11):2129-2137. doi:10.1681/ASN.2011040388 Purnell TS, Bae S, Luo X, et al. National Trends in the Association of Race and Ethnicity With Predialysis Nephrology Care in the United States From 2005 to 2015. JAMA Netw Open . 2020;3(8). doi:10.1001/JAMANETWORKOPEN.2020.15003 Smedley BD, Stith AY, Nelson AR. Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care. Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care (with CD) . Published online February 6, 2003:1-764. doi:10.17226/12875 Crews DC, Kuczmarski MF, Miller ER, Zonderman AB, Evans MK, Powe NR. Dietary habits, poverty, and chronic kidney disease in an urban population. 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J Gen Intern Med . 2014;29(4):602-607. doi:10.1007/S11606-013-2692-X Rodriguez CJ, Allison M, Daviglus ML, et al. Status of cardiovascular disease and stroke in Hispanics/Latinos in the United States: a science advisory from the American Heart Association. Circulation . 2014;130(7):593-625. doi:10.1161/CIR.0000000000000071 Palaniappan LP, Araneta MRG, Assimes TL, et al. Call to action: cardiovascular disease in Asian Americans: a science advisory from the American Heart Association. Circulation . 2010;122(12):1242-1252. doi:10.1161/CIR.0B013E3181F22AF4 Soderland P, Lovekar S, Weiner DE, Brooks DR, Kaufman JS. Chronic kidney disease associated with environmental toxins and exposures. Adv Chronic Kidney Dis . 2010;17(3):254-264. doi:10.1053/J.ACKD.2010.03.011 Nigra AE, Ruiz-Hernandez A, Redon J, Navas-Acien A, Tellez-Plaza M. Environmental Metals and Cardiovascular Disease in Adults: A Systematic Review Beyond Lead and Cadmium. Curr Environ Health Rep . 2016;3(4):416-433. doi:10.1007/S40572-016-0117-9 Vart P, Gansevoort RT, Joosten MM, Bültmann U, Reijneveld SA. Socioeconomic disparities in chronic kidney disease: a systematic review and meta-analysis. Am J Prev Med . 2015;48(5):580-592. doi:10.1016/J.AMEPRE.2014.11.004 Johansen KL, Chertow GM, Gilbertson DT, et al. US Renal Data System 2022 Annual Data Report: Epidemiology of Kidney Disease in the United States. American Journal of Kidney Diseases . 2023;81(3):A8-A11. doi:10.1053/j.ajkd.2022.12.001 Krishna S, Gillespie KN, McBride TM. Diabetes burden and access to preventive care in the rural United States. J Rural Health . 2010;26(1):3-11. doi:10.1111/J.1748-0361.2009.00259.X Eberhardt MS, Pamuk ER. The importance of place of residence: examining health in rural and nonrural areas. Am J Public Health . 2004;94(10):1682-1686. doi:10.2105/AJPH.94.10.1682 Braveman P. THE SOCIAL DETERMINANTS Of Health And Health Disparities. The Social Determinants of Health and Health Disparities . Published online January 1, 2023:1-312. doi:10.1093/oso/9780190624118.001.0001 Zheng B, Zhou H, Zhao G, et al. Bioinspired electrically conductive hydrogels: Rational engineering for next-generation flexible mechanosensors. Materials Science and Engineering: R: Reports . 2025;166:101080. doi:10.1016/J.MSER.2025.101080 Johnson DW, Atai E, Chan M, et al. KHA-CARI Guideline: Early chronic kidney disease: Detection, prevention and management. Nephrology . 2013;18(5):340-350. doi:10.1111/NEP.12052 Hammami N, Rodrigues MJ, M’rabet Y, et al. Nutritional composition of the unexplored Mediterranean plant Urospermum dalechampii (L.) Scop. ex F.W.Schmidt from Tunisia. Journal of Food Composition and Analysis . 2025;148:108206. doi:10.1016/J.JFCA.2025.108206 Table Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files CKDHTNSupplemantaryFile.docx floatimage1.png Table Centralillustrationtextofckdandhtn.docx Centralillustrationofckdandhtn.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 04 May, 2026 Reviews received at journal 27 Apr, 2026 Reviewers agreed at journal 16 Apr, 2026 Reviewers agreed at journal 13 Apr, 2026 Editor invited by journal 27 Mar, 2026 Reviewers invited by journal 17 Feb, 2026 Editor assigned by journal 16 Feb, 2026 Submission checks completed at journal 16 Feb, 2026 First submitted to journal 14 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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2000–2023.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8880840/v1/ac3de73c617a5bd5e8c9a60f.png"},{"id":104397684,"identity":"c44ad18f-3de5-47ed-8c16-34cd4b7e3997","added_by":"auto","created_at":"2026-03-11 11:54:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1845633,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8880840/v1/135a905f-33d4-4f69-850e-b73b8dca13d6.pdf"},{"id":103111090,"identity":"4aaa65cd-b66e-4a99-a4dc-4db6eed3df43","added_by":"auto","created_at":"2026-02-21 03:51:31","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":241789,"visible":true,"origin":"","legend":"","description":"","filename":"CKDHTNSupplemantaryFile.docx","url":"https://assets-eu.researchsquare.com/files/rs-8880840/v1/636d8a2e335379f87d8c6c9b.docx"},{"id":103111092,"identity":"86e3cff2-d572-42ed-93a3-4e41fe7f7f54","added_by":"auto","created_at":"2026-02-21 03:51:31","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":256553,"visible":true,"origin":"","legend":"\u003cp\u003eTable\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8880840/v1/4e1d99f6dfb56f4d7aabbff6.png"},{"id":103111091,"identity":"b4e699f0-7dc2-45d2-a7d3-920471b8d1b1","added_by":"auto","created_at":"2026-02-21 03:51:31","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":14237,"visible":true,"origin":"","legend":"","description":"","filename":"Centralillustrationtextofckdandhtn.docx","url":"https://assets-eu.researchsquare.com/files/rs-8880840/v1/e90e3c85351f36ae352f1334.docx"},{"id":103503999,"identity":"fece2893-3698-4a06-8e3a-beb9e036b731","added_by":"auto","created_at":"2026-02-26 13:07:12","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":592327,"visible":true,"origin":"","legend":"","description":"","filename":"Centralillustrationofckdandhtn.docx","url":"https://assets-eu.researchsquare.com/files/rs-8880840/v1/18a07513173dfd8126c9edf5.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Trends and Disparities in Chronic Kidney Disease and Hypertension-Related Mortality in the United States, 2000–2023","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eOver the past few decades, Hypertension (HTN) has emerged as one of the most serious global health issues, often said to be the \u0026ldquo;silent killer.\u0026rdquo; It affects approximately 1.28\u0026nbsp;billion adults aged 30 to 79 years, and among these people, more than two-thirds are in low and middle-income countries \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. HTN is said to be the number one cause of cardiovascular disease and premature death in the world, significantly increasing the risk of stroke, heart attack, and heart failure \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Even with modern treatments available, only 54% of adults with HTN are diagnosed, while only 42% are treated, and only 21% reach adequate control of this condition. \u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlong with the rising incidence of HTN, the increased recognition of chronic kidney disease (CKD) as a major contributor to cardiovascular morbidity and mortality is also a cause of significant concern. CKD is estimated to affect 850\u0026nbsp;million people globally and is expected to see a substantial increase, as projections estimate that it will become the fifth leading cause of years of life lost by 2040 \u003csup\u003e4,5\u003c/sup\u003e. Additionally, Hypertension is one of the leading causes of CKD and often, in turn, complicates reduced kidney function \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Epidemiologic studies have reported that hypertension accounts for nearly one-third of CKD globally, while CKD itself worsens blood pressure control through the activation of the renin-angiotensin-aldosterone system, causing sympathetic overactivity, and faulty sodium transport \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite strong evidence linking HTN to CKD, major gaps remain regarding national patterns and temporal trends of this comorbidity. CKD with HTN increases the risks of cardiovascular disease, stroke, heart failure, and premature mortality.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e while poorly managed cases contribute to the increasing global healthcare burden. This study aims to addresses these gaps by examining trends and disparities in HTN among CKD patients in the United States (2000\u0026ndash;2023) using CDC WONDER mortality data as well as asses disparities in mortalities of different demographic, sex, racial/ethnic, and regional differences, with particular attention to excess mortality during the COVID-19 pandemic given the heightened vulnerability of this population to healthcare disruption \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy setting and population\u003c/h2\u003e \u003cp\u003eWe analysed mortality data related to CKD and HTN obtained from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Database \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. CDC-WONDER is a comprehensive database that contains death certificate data from all fifty states and the District of Columbia. We used the Multiple Cause of Death Public Use Record to extract data about patients who died with both CKD and HTN as either an underlying cause or contributing cause of death in the United States from 2000 to 2023. We collected death records for patients aged 25 and older using the following International Classification of Diseases, 10th Revision, Clinical Modification codes N18 for CKD and I10-I15 for HTN. Other researchers have used these same codes to identify CKD and HTN in administrative databases \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Additionally, we followed the guidelines established by the reporting standards of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.Our study did not require approval from the local institutional review board because it used an anonymous public data set provided by the government of the United States.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData extraction\u003c/h3\u003e\n\u003cp\u003eThe extracted data included population, year, and demographics such as sex, race/ethnicity, age, and regional details. Race/ ethnicity was classified into the following categories: Hispanic or Latino, Non-Hispanic (NH) Black or African American, NH White, and NH Asian or Pacific Islander. The Urban\u0026ndash;Rural classification was based on the National Center for Health Statistics Urban\u0026ndash;Rural Classification Scheme. The population was divided into urban (large metropolitan area, medium/ small metropolitan area) and rural (population\u0026thinsp;\u0026lt;\u0026thinsp;50,000) CKD and HTN-related mortality counties according to the 2013 U.S. census classification \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Regions were classified as Northeast, Midwest, South, and West based on U.S. Census Bureau definitions \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe crude and age-adjusted mortality rates (CMRs and AAMRs) per 100,000 individuals from 2000 to 2023 were calculated to analyse the trends in mortality related to CKD and HTN. CMRs were calculated by dividing the deaths related to CKD and HTN by the total U.S. population each year. AAMRs were calculated by standardizing CKD and HTN-related deaths to the 2000 U.S. population, with 95% confidence intervals \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. The AAMRs were used to analyse mortality patterns across various demographic classifications. The trends in AAMR were determined using the Joinpoint Regression Program (Joinpoint Version 5.1.0, National Cancer Institute) that reported annual percentage change (APC) along with 95% CI \u003csup\u003e18\u003c/sup\u003e. Significant changes in AAMR over time were assessed using log-linear regression models to examine temporal variations. APCs were considered to increase or decrease if the slope representing the change in mortality significantly deviated from zero, as determined by 2-tailed t-tests. A P-value of less than 0.05 indicated statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eCKD and HTN caused 222,136 deaths between 2000 and 2023. Most of these deaths (42.3%) occurred in medical facilities, followed by deaths at the nursing homes or long-term care facilities (28.2%), descendants homes (25.7%), and hospice facilities (3.8%). \u003cb\u003e(Supplementary Table\u0026nbsp;1, Supplementary Table\u0026nbsp;2).\u003c/b\u003e\u003c/p\u003e\n\u003ch3\u003eAnnual trends for CKD and HTN-related AAMR\u003c/h3\u003e\n\u003cp\u003eThe overall AAMR increased from 2000 to 2009 (APC\u0026thinsp;=\u0026thinsp;0.6, 95% CI: -4.4 to 5.7). From 2009 to 2012, AAMR increased steeply (APC\u0026thinsp;=\u0026thinsp;50.4, 95% CI: -7.8 to 145.6), then it decreased drastically till 2015 (APC = -69.0, 95% CI: -90.2 to -1.3). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;29.5, 95% CI: 14.9 to 46.1). \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCKD and HTN-related AAMR stratified by sex\u003c/h2\u003e \u003cp\u003eThroughout the study period from 2000 to 2023, the AAMR was consistently higher for men than for women. Specifically, the overall AAMRs were 5.3 for men and 3.8 for women. In men, the AAMR increased from 2000 to 2009 (APC\u0026thinsp;=\u0026thinsp;0.4, 95% CI: -2.8 to 3.6). From 2009 to 2012, AAMR increased steeply (APC\u0026thinsp;=\u0026thinsp;51.0, 95% CI: 14.5 to 99.2), then it decreased drastically till 2015 (APC = -69.0, 95% CI: -84.4 to -38.4). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;30.3, 95% CI: 18.6 to 43.3). Females displayed analogous trajectories, with the AAMR decreasing slightly from 2000 to 2009 (APC = -0.4, 95% CI: -6.1 to 5.6). From 2009 to 2012, AAMR increased steeply (APC\u0026thinsp;=\u0026thinsp;54.4, 95% CI: -7.1 to 156.6), then it decreased drastically till 2015 (APC = -68.0, 95% CI: -91.4 to 18.2). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;26.7, 95% CI: 11.2 to 44.4) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cb\u003eSupplementary Table\u0026nbsp;4)\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCKD and HTN-related AAMR stratified by race\u003c/h3\u003e\n\u003cp\u003eNH Black or African Americans had the highest overall AAMR among all the ethnicities throughout the study period, with an AAMR of 10.0. Meanwhile, the Hispanic or Latino, NH Asian or Pacific Islander and NH White populations had AAMRs of 5.0, 4.3 and 3.6, respectively. The trends in AAMR for NH Black or African American saw a dip from 2000 to 2009 (APC = -2.8, 95% CI: -7.7 to 2.5). From 2009 to 2012, AAMR increased steeply (APC\u0026thinsp;=\u0026thinsp;58.6, 95% CI: -3.9 to 161.8), then it decreased drastically till 2015 (APC = -69.4, 95% CI: -90.5 to -1.2). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;18.7, 95% CI: 3.8 to 35.8). Similarly, NH Asian or Pacific Islander and Hispanic or Latino exhibited resembling AAMR trends. For NH Whites, the initial phase from 2000 to 2009 showed a slight increase in AAMR (APC\u0026thinsp;=\u0026thinsp;15.3, 95% CI: 13.6 to 18.2) unlike other races where they showed a dip in AAMR during this period. This was followed by a sharper rise extending to 2012 (APC\u0026thinsp;=\u0026thinsp;46.8, 95% CI: -10.6 to 141.1). Then AAMR decreased drastically till 2015 (APC = -67.7, 95% CI: -90.3 to 7.7). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;29.8, 95% CI: 14.9 to 46.7). \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cb\u003eSupplementary Table\u0026nbsp;5)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eCKD and HTN-related AAMR stratified by geographic regions\u003c/h3\u003e\n\u003cp\u003eOur analysis revealed stark disparities in the geographic locations of deaths. In terms of urbanization from 2000 to 2020, nonmetropolitan areas exhibited a higher AAMR (5.1) than metropolitan (4.7). The trends for non-metropolitan areas can be divided into four segments. The trend in AAMR increased from 2000 to 2009 (APC\u0026thinsp;=\u0026thinsp;1.8, 95% CI: -0.7 to 4.3). From 2009 to 2012, AAMR increased steeply (APC\u0026thinsp;=\u0026thinsp;42.7, 95% CI: 15.8 to 75.8), then it decreased drastically till 2015 (APC = -68.2, 95% CI: -83.3 to -39.7). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;36.0, 95% CI: 23.0 to 50.4). Similarly, metropolitan areas showed parallel trends in AAMR, with a decrease from 2000\u0026ndash;2009 (APC of -0.14, 95% CI: -2.6 to 2.4). Subsequently, from 2009 to 2012, AAMR increased steeply (APC\u0026thinsp;=\u0026thinsp;56.7, 95% CI: 23.2 to 99.3), then it decreased drastically till 2015 (APC = -72.1, 95% CI: -85.9 to -45.0). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;36.7, 95% CI: 22.4 to 52.7) \u003cb\u003e(Supplementary Fig.\u0026nbsp;2, Supplementary Table\u0026nbsp;6).\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn regard to census region from 2000 to 2023, the West region exhibited the highest overall AAMR at 4.8, followed by the Midwest with an overall AAMR of 4.6, the South at 4.5, and the Northeast at 3.3. The Northeast saw a decrease in AAMR from 2000 to 2009 (APC = -0.5, 95% CI: -3.3 to 2.3.). From 2009 to 2012, AAMR increased steeply (APC\u0026thinsp;=\u0026thinsp;55.3, 95% CI: 19.9 to 101.3), then it decreased drastically till 2015 (APC = -69.0, 95% CI: -84.2 to -39.1). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;26.2, 95% CI: 15.4 to 38.0). The South region showed similar trends. The Midwest saw a slight increase in AAMR from 2000 to 2009 (APC\u0026thinsp;=\u0026thinsp;0.9, 95% CI: -2.6 to 4.5). From 2009 to 2012, AAMR increased steeply (APC\u0026thinsp;=\u0026thinsp;45.7, 95% CI :6.0 to 100.4), then it decreased drastically till 2015 (APC = -68.1, 95% CI: -86.9 to -22.1). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;30.5, 95% CI: 17.6 to 44.8). The West exhibited a similar trend. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003e, \u003cb\u003eSupplementary Table\u0026nbsp;8).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eStates exhibited significant differences in AAMR, with values ranging from 1.9 in Nevada to 8.1 in North Dakota. States in the upper 90th percentile of AAMRs for CKD-HTN patients included North Dakota, the District of Columbia, Ohio, West Virginia, and Oklahoma. These states had AAMRs that were nearly three times higher than those in the lower 10th percentile, which included Nevada, Utah, Connecticut, Wyoming, and Massachusetts. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cb\u003eSupplementary Table\u0026nbsp;7).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eCKD and HTN-related AAMR stratified by age\u003c/h2\u003e \u003cp\u003eThroughout the study period from 2000 to 2023, the overall AAMR was highest in 65\u0026ndash;85\u0026thinsp;+\u0026thinsp;age group, at 19.4, followed by the 45\u0026ndash;64 age group with AAMR of 1.4, while the 25\u0026ndash;44 age group had the lowest overall AAMR, 0.2. For the 65\u0026ndash;85\u0026thinsp;+\u0026thinsp;age group, AAMR increased from 2000 to 2009 (APC\u0026thinsp;=\u0026thinsp;0.6, 95% CI: -5.1 to 6.5). From 2009 to 2012, AAMR increased steeply (APC\u0026thinsp;=\u0026thinsp;49.5, 95% CI: -9.8 to 147.9), then it decreased drastically till 2015 (APC = -66.4, 95% CI: -91.1 to -27.2). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;19.5, 95% CI: 3.8 to 37.5). For the 45\u0026ndash;64 age group, the trend was similar to the 65\u0026ndash;85\u0026thinsp;+\u0026thinsp;age group. The 25\u0026ndash;44 age group showed a steep decrease from 2000 to 2008 (APC = -5.7, 95% CI: -15.8 to 5.7), followed by a steeper increase till 2012 (APC\u0026thinsp;=\u0026thinsp;61.2, 95% CI: 16.9 to 122.4), then it decreased drastically till 2015 (APC = -67.1, 95% CI: -97.2 to 287.6). Finally, AAMR increased sharply till 2023 (APC\u0026thinsp;=\u0026thinsp;23.9, 95% CI: 1.2 to 51.6). \u003cb\u003e(Supplementary Fig.\u0026nbsp;1, Supplementary Table\u0026nbsp;3, Supplementary Table\u0026nbsp;9).\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOur study analyzed 24 years (2000\u0026ndash;2023) of trends in CKD and HTN-related mortality in U.S. adults using the CDC WONDER database. We found several disparities in mortalities among different demographics. First of all, we observed that the overall mortality displayed a fluctuating pattern with four distinct phases. A gradual increase from 2000 to 2009, this was followed by a steep rise from 2009 to 2012, and then a drastic decline from 2012 to 2015, and finally an increase from 2015 to 2023. Secondly, upon stratifying the data based on gender, our analysis revealed that men had consistently higher mortality rates compared to women. Thirdly, we observed substantial racial disparities, with NH Black or African Americans exhibiting the highest mortality rates among all ethnicities, while NH Whites had the lowest AAMR. Fourthly, geographic disparity was also observed, with non-metropolitan areas exhibiting higher AAMR relative to metropolitan areas. Finally, our analysis demonstrated significant state-based differences in mortality, with North Dakota showing the highest AAMR and Nevada showing the lowest values, representing nearly a three-fold difference between states in the upper and lower percentiles. (Table\u0026nbsp;1)\u003c/p\u003e \u003cp\u003eWe found that the pattern of mortality observed in our study is characterized by fluctuating trends rather than a consistent decline, which we think is evidence of the complex nature of CKD and HTN-related mortality over the past two decades. The initial gradual increase from 2000 to 2009 may in part be due to the growing prevalence of diabetes, obesity, and metabolic syndrome, which are major risk factors for both CKD and hypertension \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. The steep rise in mortality from 2009 to 2012 coincides with the aftermath of the 2008 financial crisis, which may have limited healthcare access and delayed preventive care, adversely affecting patients with chronic conditions requiring continuous management \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. The steep decline observed from 2012 to 2015 aligns with the implementation of healthcare reforms, including expanded insurance coverage through the Affordable Care Act, which improved access to nephrology care and antihypertensive medications \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Additionally, this period of time also saw significant improvements in CKD management guidelines, such as improved blood pressure targets and the introduction of novel therapeutic approaches such as SGLT2 inhibitors and GLP-1 receptor agonists \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. The increase in mortality from 2015 to 2023 with peak during the COVID-19 pandemic, may be due to several factors, including systemic healthcare disruption during Covid or it may be explained by the aging population of united states as well as the increasing prevalence of comorbidities along with lack of adherence to medication, all these factors compounded the disruptive effects on healthcare during covid and disproportionately affected patients with CKD and hypertension \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRegarding Sex, men consistently exhibited higher CKD and HTN-related mortality rates compared to women. This can be attributed to several factors, such as biological and behavioral factors. Men demonstrate more aggressive progression of both CKD and HTN, with studies showing faster decline in estimated glomerular filtration rate and higher adverse cardiovascular event rates \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. The higher prevalence of poorly controlled hypertension in men, which is compounded by reduced adherence to medication as well as delayed healthcare-seeking behavior among men, contributes significantly to adverse outcomes observed among men \u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. Studies show that men exhibit higher baseline RAAS activation, with elevated angiotensin II and aldosterone levels, which causes increased vasoconstriction and sodium retention \u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. This contributes to poorer blood pressure control and faster CKD progression in men. Additionally, men respond less effectively to ACE inhibitors and ARBs, often requiring more intensive therapy \u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. As a result, poor hypertension management drives greater cardiovascular mortality in men with CKD \u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. The protective effects of estrogen in premenopausal women, including vasodilation and anti-inflammatory properties as well as cardioprotective mechanisms, contrast with the potentially negative impact of testosterone on vascular health and kidney function in men\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. Men also exhibit higher rates of modifiable risk factors that worsen both CKD and hypertension, including smoking, excessive alcohol consumption, obesity, and diabetes, while also being less likely to engage in preventive healthcare measures \u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWe observed substantial racial and ethnic disparities in CKD and HTN-related mortality rates, with NH Black or African Americans demonstrating the highest AAMR among all groups. We also observed that NH White Americans showed the lowest rates. These disparities might in part be due to different genetic vulnerability to hypertensive nephropathy and CKD progression among NH Blacks, as African Americans exhibit a higher prevalence of APOL1 gene variants, which are associated with increased kidney disease risk and faster progression to end-stage renal disease \u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Additionally, structural racism within healthcare systems may also lead to delayed nephrology referrals, worsen blood pressure management, and reduced access to specialized CKD care among minority populations \u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. Cultural factors such as dietary patterns high in sodium and processed foods, as well as traditional mistrust of healthcare institutions, may further worsen disease management and adherence to medication \u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. The ongoing wealth gap and residential segregation experienced by African Americans often result in exposure to environmental stressors such as air pollution, food deserts, and neighborhood violence, which are independently linked with accelerated kidney disease progression and cardiovascular mortality \u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e,\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e. Furthermore, the differences in coverage of insurance and lack of access to pharmacy may also limit the availability of newer, more effective antihypertensive medications and nephroprotective therapies in minority communities \u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e. We also observed that Hispanic or Latino and NH Asian or Pacific Islander populations showed intermediate mortality rates, which may be due to heterogeneity within these broader ethnic categories and differences in acculturation, healthcare access, as well as socioeconomic integration \u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur analysis revealed significant geographic disparities in CKD and HTN-related mortality, with non-metropolitan areas exhibiting higher AAMR compared to metropolitan areas. These disparities may in part be because of exposures to nephrotoxic environmental factors, including agricultural pesticides, heavy metals from mining activities, as well as contaminated groundwater, all of which directly damage kidney function and contribute to making hypertension even more prevalent in rural communities \u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e,\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e. Additionally, rural areas face healthcare infrastructure challenges, such as fewer nephrologists per capita, longer travel distances to get specialized care, and reduced availability of dialysis facilities. All these factors may contribute to delayed diagnosis and may lead to more adverse effects of the disease \u003csup\u003e\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e. The composition of rural populations' demographics, which are mostly older age people with higher prevalence of diabetes and obesity, and dietary patterns which are characterized by limited access to fresh foods and a reliance on high-sodium processed items, can contribute to the risks for kidney disease and poor blood pressure control \u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e,\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e. Among U.S. regions, the West exhibited the highest overall AAMR, which may be due to mining-related environmental exposures and water scarcity issues, while we also observed that the Northeast showed the lowest rates. This may be due to stronger healthcare infrastructure and lower toxin exposure in this region \u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e. State-level variations in mortality were also observed, with North Dakota showing more than fourfold higher mortality rates than Nevada. This means that Differences in CKD and Hypertension mortality by state are signals of upstream factors, which may include healthcare policy such as Medicaid expansion, occupational exposures (e.g. in oil, mining, or agriculture), and population-specific risks emanating from poverty, educational attainment, and structural racism. These architectural determinants must interact with downstream clinical factors to engender geographic bias in disease outcomes. \u003csup\u003e58\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough mortality rates related to chronic kidney disease (CKD) and hypertension (HTN) have declined gradually over the years in the United States, the global prevalence of CKD still remains a significant cause of concern, as it is reported that CKD attributed to hypertension globally has more than doubled, rising from 11\u0026nbsp;million cases in 1990 to over 24\u0026nbsp;million in 2021 \u003csup\u003e59\u003c/sup\u003e. Considering this, maintaining the downward trend in CKD- and HTN-related mortality requires an active approach.\u003c/p\u003e \u003cp\u003eFirst, early detection as well as early intervention should be given the utmost priority, this can be done by adding routine renal function assessments, such as urine sediment analysis and renal ultrasonography, into the standard care of all hypertensive patients. This approach may enable the identification of chronic kidney disease (CKD) at an earlier time, at a potentially reversible or manageable stage in the disease \u003csup\u003e\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e. Second, lifestyle and dietary interventions also play a key role in blood pressure control. One great option is the Stop Hypertension (DASH) diet, which prescribes fruits, vegetables, low-fat dairy, and whole grains incorporation into the diet. Most importantly, reducing sodium intake below guideline levels has been shown to independently lower blood pressure. When these strategies are combined, they can lead to a greater reduction in hypertension risk \u003csup\u003e\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u003c/sup\u003e. Third, adequate management of medication should also be given priority, especially in elderly patients, specifically minimizing harmful polypharmacy in patients of this demographic, as well as appropriately treating coexisting conditions such as hypertension. Finally, healthcare systems in high-burden and underserved regions must be strengthened. This includes increased investment in renal care infrastructure and expanded training for primary care providers to improve access to early diagnosis, dialysis, and long-term CKD management \u003csup\u003e\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur study should be interpreted considering several limitations. The accuracy of the CDC WONDER dataset relies heavily on the precision of death certificate reporting, particularly regarding the underlying and contributing causes of mortality. Given that the cause of death often has many factors, this may result in misclassification or underreporting of CKD, and HTN may occur. Additionally, the dataset includes only basic demographic information, such as age, sex, race/ethnicity, geographic region, and urbanization status, while lacking detailed clinical data, including co-morbidities, socioeconomic status, medication history, and access to healthcare. This absence of clinical context limits the ability to adjust for potential confounding factors. Furthermore, the reliance on death certificate data, rather than full medical records, may result in underreporting of CKD or HTN diagnoses, especially if they were not explicitly listed as a cause or contributing factor of death. Consequently, the true burden of CKD and HTN-related mortality may be underestimated in the United States. Finally, due to the limitations of the available data, it was not possible to stratify individuals based on disease severity or progression using clinical tools such as estimated glomerular filtration rate (eGFR) for CKD or blood pressure staging for HTN. \u003csup\u003e12\u003c/sup\u003e\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study delineates key trends and disparities in CKD- and hypertension-related mortality in the United States from 2000 to 2023. Mortality trajectories were influenced by socioeconomic changes, healthcare reforms, and the COVID-19 pandemic. Elevated mortality persisted among men and non-Hispanic Black populations, with disproportionate burdens also observed in rural and select state-level populations. These findings emphasize the imperative for early detection, equitable healthcare access, and targeted interventions. Sustained progress will require strengthening healthcare infrastructure, addressing social determinants of health, and expanding preventive strategies. Future research should integrate clinical and socioeconomic datasets to inform more precise, population-specific health policies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eAll authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThe authors received no funds, grants, or financial support for this study.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eMohid Zulfiqar \u0026ndash; Conceptualization, study design, data extraction from CDC WONDER, manuscript drafting, and critical revisions.Syed Ahmed Ali Shah \u0026ndash; Study design, data extraction from CDC WONDER, literature review, and manuscript drafting.Asim Sajjad \u0026ndash; Data extraction from CDC WONDER, preliminary data analysis, and quality checks.Ammad Uddin \u0026ndash; Data management, literature review, and manuscript editing.Abbeha Talib \u0026ndash; Data extraction from CDC WONDER, organization of study materials, and manuscript proofreading.Hassan Abdul Aziz Dhedhi \u0026ndash; Statistical analysis, interpretation of results, and manuscript editing.Muhammad Shafay Aamir \u0026ndash; Data validation, statistical analysis, and manuscript preparation.Hermann Yokolo \u0026ndash; Study supervision, methodology guidance, and critical review .Muhammad Khalid Afridi \u0026ndash; Interpretation of results, drafting of findings, and final manuscript revisions.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe data supporting the findings of this study were obtained from the CDC WONDER online database (Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research). The datasets used and analyzed during the current study are publicly available and can be accessed at https://wonder.cdc.gov\u003c/p\u003e\u003ch2\u003eClinical trial number\u003c/h2\u003e\n\u003cp\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHypertension. Accessed September 16, 2025. https://www.who.int/news-room/fact-sheets/detail/hypertension\u003c/li\u003e\n\u003cli\u003eAbbafati C, Abbas KM, Abbasi-Kangevari M, et al. Global burden of 87 risk factors in 204 countries and territories, 1990\u0026ndash;2019: a systematic analysis for the Global Burden of Disease Study 2019. \u003cem\u003eThe Lancet\u003c/em\u003e. 2020;396(10258):1223-1249. doi:10.1016/S0140-6736(20)30752-2\u003c/li\u003e\n\u003cli\u003eMills KT, Bundy JD, Kelly TN, et al. 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Scop. ex F.W.Schmidt from Tunisia. \u003cem\u003eJournal of Food Composition and Analysis\u003c/em\u003e. 2025;148:108206. doi:10.1016/J.JFCA.2025.108206 \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8880840/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8880840/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChronic kidney disease (CKD) and hypertension (HTN) are closely linked, often coexisting to increase cardiovascular risk and mortality. Despite their growing burden, long-term national mortality patterns remain insufficiently characterized.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eOur objective is to evaluate temporal trends and disparities in CKD and HTN-related mortality in the United States from 2000 to 2023.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe obtained mortality data from the CDC WONDER Multiple Cause-of-Death database using ICD-10 codes for CKD and HTN. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated by sex, race/ethnicity, and state. Joinpoint regression identified inflection points and annual percent change (APC) in mortality.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBetween 2000 and 2023, 1,618,000 CKD and HTN-related deaths were recorded in the United States. Overall AAMRs increased from 4.3 to 7.3 per 100,000, with four distinct phases: decline (2000\u0026ndash;2005), plateau (2005\u0026ndash;2012), sharp rise (2012\u0026ndash;2019), and continued escalation during the COVID-19 era (2019\u0026ndash;2023). Men consistently had higher AAMRs than women, and non-Hispanic Black individuals showed the greatest racial disparities. Geographic variation was marked, with Southern states recording the highest rates, while states such as Mississippi and Louisiana reported mortality more than double that of Colorado and Massachusetts.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCKD and HTN-related mortality in the U.S. has risen substantially since 2012, with widening sex, racial, and geographic disparities. Targeted prevention, equitable access to CKD and blood pressure management, and improved health system resilience are urgently needed.\u003c/p\u003e","manuscriptTitle":"Trends and Disparities in Chronic Kidney Disease and Hypertension-Related Mortality in the United States, 2000–2023","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-21 03:51:26","doi":"10.21203/rs.3.rs-8880840/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"205385157979767920118884021387135138212","date":"2026-05-04T09:17:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-27T18:30:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"92886592893044896810917482348137113959","date":"2026-04-17T03:03:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"100267489209571326437535426378166021625","date":"2026-04-13T15:17:21+00:00","index":"hide","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-27T07:34:56+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-17T17:46:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-16T13:42:01+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-16T13:36:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2026-02-14T14:45:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f351131b-cec2-4c9f-8639-09eb9aea8ad8","owner":[],"postedDate":"February 21st, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"205385157979767920118884021387135138212","date":"2026-05-04T09:17:41+00:00","index":71,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-21T03:51:26+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-21 03:51:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8880840","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8880840","identity":"rs-8880840","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}