Global Burden Of Chronic Kidney Disease Due To Hypertension From Year 1990 To 2021 and Implications From Disparities Across Regions

doi:10.21203/rs.3.rs-5301262/v1

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Global Burden Of Chronic Kidney Disease Due To Hypertension From Year 1990 To 2021 and Implications From Disparities Across Regions

https://doi.org/10.21203/rs.3.rs-5301262/v1

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Background:

Chronic Kidney Disease due to hypertension poses a growing global diseaseburden, with significant disparities across regions. Comprehensive analysis and effective strategies should be provided to tackle the increasing issue.

Methods:

Using data from the Global Burden of Disease 2021, this study conducted descriptive and statistical analyses to evaluate the CKD burden due to hypertension across different SDI regions. EAPC,risk factors and decomposition were used to analyse the tread and distributional difference

Findings:

Globally, ASMR increased from 4.29 (95% UI: 3.55–5.11) per 100,000 in 1990 to 5.54 (95% UI: 4.68–6.41) in 2021, with a 0.97% annual increase. High SDI regions saw a sharp rise, with ASMR climbing from 2.4 (95% UI: 1.95–2.86) to 4.09 (95% UI: 3.34–4.71) and an EAPC of 2.23%. Low SDI regions experienced a slight decline in ASMR from 8.69 (95% UI: 7.03–10.73) to 8.62 (95% UI: 7.09–10.51). High systolic blood pressure and kidney dysfunction have consistently been the leading risk factors, female have a higher risk of high body-mass index than men, especially in high SDI regions.Decomposition highlights aging and epidemiological shifts，East Asia demonstrated a unique trend, with a 49.59% reduction in ASMR, ASDR and ASPR despite an aging population, reflecting successful interventions.

According to the 2020 WHO report, CKD has become one of the top 10 leading causes of death.CKD due to hypertension is one of the main types of chronic kidney disease^[1–2]. CKD is defined as kidney damage or GFR < 60 ml/min/1.73 m2 for more than 3 months, and kidney damage is described as abnormal renal function^[3] .CKD due to hypertension is a disease caused by long-term small artery and small artery damage caused by increased blood pressure, resulting in arterial lumen stenosis and secondary ischemic renal parenchymal damage and leading to glomerulosclerosis, tubular atrophy and renal interstitial fibrosis^[4–5]. Research^[6] has shown that between 1990 and 2017, the global all-age mortality rate from CKD increased by 41.5%. Hypertension is a major risk factor for CKD, accounting for 43.2% (42.3–54.1%) of the ASDR in 2017. It was highly advocated attention globally^[7–10] Global health management is influenced by diverse factors, such as ethnicity, economics, politics, health systems, culture, and religion. Analysis of disparities in CKD caused by hypertension across nations reveals factors contributing to inequalities and areas requiring urgent interventions. This research aims to fill knowledge gaps by comprehensively examining the burden, evolution, and inequalities of CKD due to hypertension globally.

2.1. Data source

In this analysis, which is based on the Global Burden of Disease Study (GBD) 2021^[11–12], we utilized repeated cross-sectional data sourced from the Global Health Data Exchange (GHDx), as reported by the GBD 2021 Diseases and Injuries Collaborators. The GHDx offers an extensive dataset that details the global burden of 369 diseases and injuries, CKD due to hypertension mellitus, across 21 GBD regions and 204 countries and territories from 1990–2021 (updated to reflect the latest data available).

2.2. Statistical analysis

We performed descriptive analyses to characterize the burden of CKD due to hypertension and R software to construct the plot. The data for this analysis were sourced from the Global Burden of Disease (GBD) 2021 study. ASIR, ASPR, ASMR were expressed as the number per 100,000 population with a 95% uncertainty interval (UI) and ASDR expressed as the DALY year per 100,000 population.

we used EAPC^[13] to evaluate the trends over time.The natural logarithm of the rates was calculated by using the following regression model, y = α + βx + ε, where y denotes ln (ASR), x denotes the calendar year, and ε denotes the error term; estimated annual percentage change (EAPC) = 100×(exp(β)-1); moreover, its 95%

confidence interval (CI) can also be obtained from the above method.

The Kruskal-Wallis test was used to compare differences in ASIR, ASPR, ASDR, and ASMR among the five SDI regions.

We used two-sided maps to demonstrate the attributable DALY and the proportion of attributable Deaths for each risk factor.

Decomposition Analysis^[14] was applied to help understand how different factors affect the overall change, it can divide the changes in the number of people getting sick over a certain period of time into including population age structure, population growth, and changes in epidemic trends. Decomposition analysis is a method used to understand the patterns and changes in the data. Through mathematical decomposition techniques, the overall changes are decomposed into multiple parts to identify the specific contributions of each part.

We analyzed the relationship of different SDI and disease burden by linear fitting and demonstrated variation across years across 21 GBD regions worldwide.

3.1. Global Trend of Chronic Kidney Disease (CKD) Due to Hypertension

From 1990 to 2021, global health indicators experienced significant changes, with the global death rate increasing from 148,983 (95%UI 123,167 to 176,985) to 454,359 (95%UI 381,291 to 524,688), DALYs rising from 4,344,896 (95%UI 3,676,494 to 5,110,004) to 24,467,653 (95%UI 22,861,634 to 26,230,869), prevalence growing from 11,712,345 (95%UI 10,891,658 to 12,623,876) to 24,467,653 (95%UI 22,861,634 to 26,230,869), and incidence also increasing from 463,924 (95%UI 426,189 to 505,831) to 1,282,205 (95%UI 1,195,230 to 1,366,296). These changes not only reveal the intensification of global health challenges but also highlight the diversity and complexity of different regions in addressing these challenges. At the regional level, South Asia saw a significant increase in death rates, from 14,238 (95%UI 10,767 to 17,766) to 43,580 (95%UI 33,263 to 55,429), Southeast Asia, East Asia, and Oceania experienced a notable rise in DALYs, from 1,875,328 (95%UI 1,562,765 to 2,208,013) to 6,730,205 (95%UI 6,232,881 to 7,280,394), prevalence in South Asia also increased significantly, from 7,773,790 (95%UI 7,165,250 to 8,385,000) to 20,008,090 (95%UI 18,455,882 to 21,496,060), and Sub-Saharan Africa had a marked increase in incidence, from 19,265 (95%UI 15,673 to 23,203) to 47,376 (95%UI 39,181 to 56,014). These figures reflect the diversity in health challenges and the complexity of response strategies across different regions(Table 1 ).

Generally, as SDI decreases, ASDR generally increases, and it also increases overall over the years. However, after 2010, the ASDR in high SDI regions became higher than in high-middle SDI regions, indicating a shift in the health burden. The trend for ASMR is similar to that of ASDR.In terms of ASPR, high-middle SDI is lower, while the other four SDIs are generally higher. Over time, there is a significant decline in high-middle SDI, while the other four groups show little change.Regarding ASIR, as SDI increases, ASDR generally increases, and it also gradually increases over the years.ASMR increased from 4.29 (3.55, 5.11) to 5.54 (4.68, 6.41) in global, with an EAPC of 0.97 (0.91, 1.03). Notably, the High SDI region experienced a marked rise from 2.4 (1.95, 2.86) to 4.09 (3.34, 4.71), with an EAPC of 2.23 (2.07, 2.39). The Central Europe, Eastern Europe, and Central Asia region showed a particularly sharp increase in mortality rates, with an EAPC of 1.61 (1.39, 1.83). Conversely, the Low SDI region exhibited a slight decrease in mortality rates, from 8.69 (7.03, 10.73) to 8.62 (7.09, 10.51), with an EAPC of -0.08 (-0.2, 0.04).ASDR increased from 107.77 (91.26, 126.92) in 1990 to 128.41 (109.14, 145.64) in 2021, with an EAPC of 0.63 (0.58, 0.67). The High SDI region showed a significant rise, with DALYs rates increasing from 54.18 (46.63, 61.64) to 84.75 (74.6, 94.25), and an EAPC of 1.83 (1.71, 1.95). The Low SDI region, however, demonstrated a decrease, with DALYs rates dropping from 191.83 (156.62, 233.69) to 181.48 (150, 219.11), and an EAPC of -0.29 (-0.38, -0.19). ASPR generally showed a downward trend. Globally, prevalence rates decreased from 310.68 (289.07, 333.84) to 291.19 (272.49, 311.88), with an EAPC of -0.16 (-0.18, -0.13). The High-middle SDI region stood out with a significant decrease in prevalence, from 283.65 (264.47, 305.48) to 246.07 (229.28, 263.95), and an EAPC of -0.37 (-0.41, -0.33). The Southeast Asia, East Asia, and Oceania region experienced a substantial decline in prevalence rates, with an EAPC of -0.4 (-0.49, -0.32).ASIR mostly increased across the board. Globally, incidence rates rose from 12.24 (11.31, 13.33) to 14.97 (14.02, 15.93), with an EAPC of 0.66 (0.66, 0.67). The High SDI region saw a moderate increase, with incidence rates climbing from 16.83 (15.57, 18.35) to 18.85 (17.6, 20.1), and an EAPC of 0.34 (0.3, 0.38). The North Africa and Middle East region, however, had the most significant increase in incidence rates, from 15.77 (14.36, 17.27) to 25.72 (23.77, 27.66), with an EAPC of 1.55 (1.47, 1.62).

( Fig. 1 and Fig. 2 )

The figure displays the relationship between mortality and the SDI for various global regions from 1990–2021, illustrating regional disparities in health outcomes over time.The figure illustrates a general downwards trend in ASDR and ASMR as the SDI increased from 1990–2021. However, between SDIs of 0.35 and 0.6 and above an SDI of 0.8, there is a rebound in ASDR and ASMR. This suggests that despite overall improvements in health outcomes, certain regions or countries with moderate to high SDI face challenges in reducing the burden of CKD.

3.2 Segmented Distribution

The Kruskal-Wallis test has revealed significant disparities in key health indicators among countries across different SDI regions. When considering the entire population, the Age-Standardized Mortality Rate (ASMR, χ 2 = 144.3966906; df = 4; p < 0.0001), Age-Standardized Disability Rate (ASDR, χ 2 = 145.3409744; df = 4; p < 0.0001), Age-Standardized Prevalence Rate (ASPR, χ 2 = 127.1246215; df = 4; p < 0.0001), and Age-Standardized Incidence Rate (ASIR, χ 2 = 127.7019992; df = 4; p < 0.0001) all demonstrated significant differences among countries in various SDI regions, indicating that at least four groups showed substantial variation in these health metrics. Looking at gender-specific groups, both "Male" and "Female" populations also exhibited similar trends, with significant differences in the aforementioned health indicators across different SDI regions. Generally, data from 2021 suggest that higher-middle and high SDI regions have higher ASIRs, which may reflect challenges in disease control and prevention in these areas; whereas lower-middle and middle SDI regions have higher ASMRs, potentially pointing to urgent needs in providing basic medical services and improving living conditions in these regions.

Males generally had higher rate in deaths, DALYs, prevalence, and incidence compared to females, both globally and across different SDI regions. This was particularly evident in low SDI regions, where males had significantly higher DALYs and incidence rates than females.

3.3 Risk Factors for CKD Due to Hypertension

In the data from both 1990 and 2021 globally, high systolic blood pressure and kidney dysfunction have consistently been the leading risk factors for death. In 1990, high systolic blood pressure accounted for 24.61% of total deaths among males and 26.16% among females worldwide, while kidney dysfunction represented 36.01% and 35.34% respectively. By 2021, high systolic blood pressure constituted 26.55% of total deaths among females and 25.36% among males globally, with kidney dysfunction's impact being 32.52% for females and 33.06% for males. Additionally, the influence of high body-mass index significantly rose in high SDI areas, representing 16.09% and 16.26% of total deaths among females and males in 2021, a proportion lower in 1990. Dietary factors, including high sodium intake and low intake of fruits and vegetables, impacted both years, but their influence was intensified in 2021, especially in high SDI regions. Environmental factors, such as the effects of high and low temperatures, were relatively minor in 1990 but showed an increase by 2021. In low SDI areas, kidney dysfunction and high systolic blood pressure continue to dominate, reflecting disparities in medical resources and health awareness. These data indicate that lifestyle and environmental factors are increasingly affecting global health, while high systolic blood pressure and kidney dysfunction persist as major risk factors for mortality.

Risk factors contributed to DALYs for the years 2021 and 1990 shows that high systolic blood pressure and kidney dysfunction have consistently been leading factors (Fig. 3).

For instance, in 2021, high systolic blood pressure accounted for 24.94% and 25.66% of DALYs in males and females globally, respectively, while kidney dysfunction had an impact of 34.16% and 33.51%. The impact of high Body Mass Index (BMI) significantly rose in high SDI regions, contributing to 12.53% and 14.23% of DALYs in males and females in 2021, respectively. Dietary factors, such as high sodium intake and low consumption of fruits and vegetables, were significant in both years but saw an increase in impact by 2021. Environmental factors like heat and cold also showed increased impacts. In low SDI regions, the impact of kidney dysfunction and high systolic blood pressure remained dominant, reflecting differences in medical resources and health awareness. Obesity and diabetes are particularly severe issues in high SDI regions, emphasizing the need for healthy diets and physical activity.

Risk factors in different region have their own features^[15–17],both global perspective and specific view should be taken to look deep into the sight.

3.4 Decomposition Analysis

Decomposition Analysis on 21GBD regions shows significant features(Fig. 4).

The global overall difference in DALYs is significant, with South Asia showing significant contributions from aging and population growth. East Asia has a significant negative impact from epidemiological changes on DALYs, accounting for − 82.79%, which may reflect improvements in disease control and health management in the region. In terms of the number of deaths, the global overall difference is also significant, with East Asia showing a significant positive contribution from aging, while Central Africa has a relatively small impact from aging on the number of deaths, but a significant contribution from population growth. The global overall difference in prevalence is huge, with South Asia leading at 1,223,429 people, with aging and population growth contributing 31.38% and 77.70%, respectively. East Asia has a very high contribution from aging to prevalence, reaching 99.74%, while epidemiological changes have a significant negative impact, accounting for − 49.59%. The global overall difference in incidence is highest in East Asia, at 81,008.84 people, with aging and population growth accounting for 56.15% and 27.39%, respectively. Central America and the Caribbean have a contribution of 32.96% from aging to incidence, 43.27% from population growth, and a significant impact from epidemiological changes, accounting for 23.77%. Changes in the global health burden reveal significant differences between regions, especially in High-income North America and High-income Asia Pacific. In High-income North America, aging and population growth contribute about 19% and 24%, respectively, to the overall increase in DALYs, while the impact of epidemiological changes is as high as 56%, which may be closely related to the increase in chronic and non-communicable diseases. In contrast, in High-income Asia Pacific, the impact of aging on the increase in DALYs is extremely significant, reaching 116%, although the contribution of population growth is lower, at 23%, but epidemiological changes are negative, reducing by 38%, indicating that the region has achieved results in controlling certain diseases.

East Asia shows some unique characteristics and advantages in health indicators: in terms of mortality, aging has a very high positive impact on the number of deaths, showing a clear trend of population aging in the region; while in DALYs, although aging and population growth have significant positive contributions to the health burden, epidemiological changes show a very negative impact (-82.79%), which may indicate that East Asia has made positive progress in disease prevention and control; in terms of prevalence, the impact of aging and population growth is significant, but the negative impact of epidemiological changes is particularly significant (-49.59%), reflecting the region's success in improving public health and disease management; in terms of incidence, East Asia also shows significant impacts of aging and population growth, while the impact of epidemiological changes is positive, indicating that the region has also achieved results in reducing the incidence of new cases. These characteristics and advantages may be related to investments in public health policies, healthcare systems, and health promotion activities in East Asia, which help to improve the health level and quality of life of residents.

Disparities in CKD Burden due to hypertensive in SDI, age and sex：

CKD affects development in countries with different SDI levels.^[18-19].The SDI is a composite measure used to assess the socioeconomic development of countries or regions. It combines indicators of income, education, and fertility rates to reflect a population's overall socioeconomic status. The SDI is used in global health studies^[20] ^[16]to understand and compare health outcomes across different levels of sociodemographic development. For the world's most populous country, increasing attention has also been given to chronic kidney disease^[15,21]. The prevention, diagnosis, control, and prognostic care of kidney disease is very urgent, especially for the hypertensive population^[22-24]. Low SDI regions, reflects disparities in healthcare access, economic development, and public health interventions. Additionally, cultural factors, health system limitations, and socioeconomic barriers further hinder effective disease management, leading to higher mortality and disability rates.In contrast, high SDI regions, while experiencing lower overall CKD burden, face challenges related to the increasing prevalence of hypertension and CKD due to aging populations and lifestyle factors. The increase in DALYs in these regions is largely attributable to population aging, with a significant proportion of the burden driven by older adults who are at higher risk for both hypertension and CKD. However, the availability of advanced healthcare services in these regions mitigates some of the impact,may result in lower mortality rates compared to low SDI regions.

The study also highlights significant sex differences in the burden of CKD due to hypertension, with males consistently exhibiting higher mortality and DALY rates than females. This disparity is more pronounced in low SDI regions, where males are disproportionately affected by risk factors such as high systolic blood pressure and kidney dysfunction. Environmental and lifestyle factors, including higher rates of tobacco use, alcohol consumption, and occupational hazards among males, contribute to this disparity. Additionally, biological differences in the progression of CKD may play a role, with males potentially experiencing faster disease progression and higher susceptibility to the adverse effects of hypertension on kidney function.

Impact of Epidemiological and Demographic Factors：

Epidemiological changes, such as the increasing prevalence of non-communicable diseases (NCDs) like hypertension, have a profound impact on the global burden of CKD. The decomposition analysis reveals that aging and population growth are major contributors to the increase in CKD-related DALYs, particularly in high SDI regions where the population is aging rapidly. In these regions, the burden of CKD is expected to continue rising as the population ages, necessitating the development of targeted interventions to manage the disease effectively.

In low SDI regions, population growth is the primary driver of the increase in CKD burden, with significant contributions from epidemiological factors. The negative impact of epidemiological changes in these regions suggests that while some progress has been made in controlling infectious diseases, the rising prevalence of NCDs poses a new challenge. Addressing this challenge requires a multifaceted approach, including strengthening health systems, improving access to preventive services, and promoting healthy lifestyles, which clinical guideline and national public policy should be involved^[25].

Policy Implications and Recommendations：

To reduce the burden , it is essential to implement comprehensive public health strategies that address the underlying risk factors and improve access to care. In low and middle-income countries, efforts should focus on expanding access to early diagnosis and treatment for hypertension and CKD, particularly in rural areas. This includes increasing the availability of primary care services and implementing community-based interventions to promote healthy behaviors.In high-income countries, policies should focus on managing the impact of population aging on CKD burden. This includes developing age-specific guidelines for the management of hypertension and CKD, promoting the use of preventive measures such as regular blood pressure monitoring and lifestyle modifications, and ensuring that healthcare systems are equipped to handle the increasing demand for CKD-related services. In Asia, proper strategy ^[26-27]highlights the distinct features such as increased vulnerability to obesity and salt sensitivity, which exacerbate its cardiovascular and renal implications. It underscores the necessity for tailored hypertension management strategies in Asia, advocating for lifestyle interventions, home blood pressure monitoring, and treatments like diuretics for salt-sensitive individuals, alongside considering renal denervation for those with resistant hypertension.

Global practice also shows that better community-level support in the form of physicians, nephrologists, and dialysis centers is needed for timely assessment of the diagnosis and progression of CKD, control of blood pressure, and regular dialysis, which may reduce the load on emergency departments for hypertensive crises.^[28] Establishing cooperative relationships with secondary and tertiary medical institutions is associated with increased awareness, treatment, and control rates of hypertension.^[27,29-30]

Targeted CKD screening for individuals with hypertension and diabetes is a more economically viable strategy that has been implemented in many countries, but fewer than a quarter (24%) of countries have established CKD detection programs on the basis of national guidelines or policies^[31-32]. This requires more initiatives. Moreover, global health initiatives should prioritize research on the social determinants of health that contribute to CKD disparities across regions. This includes examining the impact of socioeconomic factors, healthcare access, and cultural practices on the management and outcomes of CKD. By addressing these determinants, policymakers can develop more targeted and effective interventions to reduce the burden of CKD due to hypertension.

The disparities in CKD burden across different sociodemographic regions highlight the importance of tailored interventions that consider regional contexts and specific risk factors. By improving access to care, enhancing early diagnosis and treatment, and addressing the social determinants of health, it is possible to reduce the impact of CKD due to hypertension and improve health outcomes worldwide.

Limitations

The disease burden may be influenced by the evolution and progression patterns of different stages of kidney disease^[33], which requires further research. Additionally, during the study period ,it may have been affected by specific events such as COVID-19 and the varying impacts of international kidney disease organizations globally.

CKD: chronic kidney disease

DALYs: Disability-Adjusted Life Years

ASMR: Age-Standardized Mortality Rate

ASDR: Age-Standardized DALYs Rate

ASIR: Age-Standardized Incidence Rate

ASPR: Age-Standardized Prevalence Rate

SDI: sociodemographic index

Interpretation:

Prudent study underscores targeted public health interventions and comprehensive management strategies. This demonstrates the potential for effective healthcare systems to mitigate the burden, even in regions with substantial demographic shifts and SDI gaps, in implementing proper actions to tackle health inequalities in CKD burden due to hypertension.

Availability of data and materials

The data used in this study came from a public database in which everyone can access through the link provided in this article (https://vizhub.healthdata.org/gbd-results/).

Acknowledgements

We are grateful for the work of the Global Burden of Disease study 2021.

Collaborators and Chief Ping Fu of the Nephrology Department of West China Hospital of Sichuan University and Prof Hui Yang of Monash University, Australia, for supporting this study.

Authors’ contributions

RX designed the research and was a major contributor in writing the manuscript. LL and HW guided the discussion. WX and ZX discussed the results. WZ modified the expression . All authors participated in the design of the study, contributed to the drafting of the paper and approved the final manuscript.

Funding

Project 1: National Natural Science Fund for Medical Research titled :Dynamic Monitoring and Policy Intervention of Chronic Disease Comorbidity Medical and Health Services with Digital Technology Support (72342014)

Project 2: Sichuan Provincial Research Center for the Development of Primary Health Care (SWFZ20-Z-002)

Ethics approval

The GBD 2021 study is a publicly available database, and all the data were anonymized.

Consent for publication

Not applicable.

Competing interests

There are no competing interests to declare. The research was conducted without any commercial or financial relationships that could be construed as potential conflicts of interest.

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Table 1 is available in the Supplementary Files section.

No competing interests reported.

Table1numbersagestandardizedrateandEAPCofburden.xlsx

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Global Burden Of Chronic Kidney Disease Due To Hypertension From Year 1990 To 2021 and Implications From Disparities Across Regions

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Version 1

Abstract

Figures

1. Introduction

2. Methods

2.1. Data source

2.2. Statistical analysis

3. Results

3.1. Global Trend of Chronic Kidney Disease (CKD) Due to Hypertension

3.2 Segmented Distribution

3.3 Risk Factors for CKD Due to Hypertension

3.4 Decomposition Analysis

4 Discussion

Disparities in CKD Burden due to hypertensive in SDI, age and sex：

Impact of Epidemiological and Demographic Factors：

Policy Implications and Recommendations：

Conclusion

Limitations

Abbreviations

Declarations

References

Table

Additional Declarations

Supplementary Files

Status:

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