Global Burden and Health Inequalities of Heart Failure Attributable to Chronic Kidney Disease: A Comprehensive Analysis from 1990 to 2021

Abstract

Background

Limited data are available regarding the global burden of heart failure attributable to chronic kidney disease (CKD-HF). The aim of this study was to estimate the disease burden and cross-national disparities in CKD-HF from 1990 to 2021.

Methods

CKD-HF prevalence and years lived with disability (YLDs) were extracted from the Global Burden of Disease (GBD) database. The slope index of inequality and concentration index were adopted for analyzing absolute and relative health inequalities, and the autoregressive integrated moving average model was applied to project trends in CKD-HF burden through 2040.

Results

From 1990 to 2021, the CKD-HF age-standardized prevalence rate (ASPR) globally increased from 13.58 per 100,000 (95% uncertainty interval [UI]: 11.16–16.22) to 24.21 (95% UI: 19.86–29.23), and the age-standardized YLD (ASYR) increased from 1.73 (95% UI: 1.12–2.56) to 3.07 (95% UI: 1.95–4.44). By 2040, the global ASPR is projected to increase to 30.90 (95% confidence interval [CI]: 29.62–32.18), with the ASYR expected to increase to 3.84 (95% CI: 3.59–4.08). In 2021, the highest ASPRs were observed in Western Sub-Saharan Africa, Andean Latin America, and Central Latin America, whereas the highest ASYRs were observed in Australasia, Tropical Latin America, and Andean Latin America. Diabetic nephropathy and hypertensive nephropathy have emerged as increasingly significant drivers of the CKD-HF burden. The CKD-HF burden exhibited significant health inequities, with low-sociodemographic index regions bearing a disproportionate share of the burden, a trend that is expected to persist through 2040.

Conclusion

Patients with CKD-HF exhibited a sustained increase in disease burden, a shift in the underlying cause distribution, and significant health disparities. There is an urgent need for more region-specific strategies to prevent the underlying causes and improve medical care for patients with CKD-HF to mitigate the future burden of this condition.

Introduction

Chronic kidney disease (CKD) is a global public health challenge that imposes intolerably high costs on individuals, healthcare systems and society. CKD affects nearly 850 million people [1], accounting for approximately 10% of the global population, and its prevalence exceeds that of any of the other noncommunicable diseases (NCDs) currently prioritized by the World Health Organization (WHO): chronic respiratory diseases, cardiovascular diseases, diabetes, and cancer [2–4]. CKD is a leading cause of death worldwide, and one of the few NCDs that has exhibited a sustained increase in age-adjusted mortality over the past 2 decades [3–5]. According to the Global Burden of Disease (GBD) study, kidney dysfunction was responsible for 3.6 million deaths globally in 2021, ranking from 18th in 1990 to 7th in 2021, and it is expected to become the 5th most prominent cause of death worldwide through 2050 [6, 7]. Years of life lost (YLLs), a measure of premature mortality, due to CKD are projected to double from 2016 to 2040, exceeding the growth rate of all other major NCDs [8]. CKD treatment costs, including conservative kidney management and kidney replacement therapy (KRT), are projected to account for 1.6–26.6% of national healthcare expenditures by 2027, exceeding USD 400 billion [9]. Notably, the burden of CKD disproportionately falls upon socially disadvantaged and other vulnerable populations [10]. Enormous disparities in the accessibility, affordability and quality of kidney disease prevention and early diagnosis; conservative kidney management, KRT, infrastructure and service delivery; healthcare workforce; and health recognition contribute to persistently high CKD prevalence, mortality, and complication rates in resource-limited and low-income countries [11–13].

Heart failure (HF) is a prevalent complication of CKD and further serves as a significant contributor to CKD progression and associated mortality [14–16]. The interplay between HF and CKD is driven by shared etiological factors, such as hypertension and diabetes, alongside intertwined pathophysiological interactions. CKD promotes left ventricular remodeling, fibrosis, and cardiac dysfunction via fluid overload, anemia, uremia, and heightened activation of the sympathetic nervous and renin-angiotensin-aldosterone humoral systems [17]. Conversely, HF contributes to CKD progression through reduced renal perfusion, impaired hemodynamics, and ischemic injury [18]. This bidirectional relationship establishes a pathophysiological synergy, wherein the presence of one condition accelerates the progression of the other. The incidence of new-onset HF in patients with CKD ranges from 17% to 21%, with its occurrence being influenced by the severity of CKD and the modality of KRT [19, 20]. The Atherosclerosis Risk in Communities (ARIC) study revealed that the incidence of HF in individuals with an estimated glomerular filtration rate <60 mL/min/1.73 m² is 3-fold greater than that in those with preserved kidney function [19]. The prevalence of HF in patients on maintenance hemodialysis is approximately 45%, which is 36 times greater than that reported in the general population [21]. In a large prospective cohort of adults with CKD, the hospitalization for HF rate was 5.8 per 100 person-years, with 20.6% of patients being readmitted for HF within 30 days [22]. HF hospitalizations were independently linked to a 6-fold higher risk of progression to end-stage kidney disease and a 3- to 5-fold higher risk of mortality [20].

Although the fatal interplay between CKD and HF is well recognized, epidemiological data quantifying the burden of HF attributable to CKD (CKD-HF) remain limited. Given substantial disparities in treatment accessibility, affordability, and quality, the CKD-HF burden likely varies across regions, reflecting underlying health inequalities. Assessing the burden of this dual pathology can provide valuable epidemiological evidence to inform strategies for mitigating this potentially preventable global public health issue. The CKD-HF burden remains unquantified in the GBD and other national disease burden studies, hindering evidence-based prioritization and resource allocation at the global, regional, and national levels. The aim of this study was to estimate the global disease burden and cross-national inequalities in the distribution of CKD-HF from 1990 to 2021 based on the basis of the GBD database.

Methods

Data Sources

In the GBD 2021 (https://vizhub.healthdata.org/gbd-results/), led by the Institute for Health Metrics and Evaluation at the University of Washington, the health loss attributed to 371 diseases and injuries was systematically quantified using data from 100,983 sources across 204 countries and territories to inform healthcare system improvements and address disparities [23]. In the GBD study, raw data from health service records, disease-specific registries, vital registration statistics, household surveys, censuses, and other sources were integrated using statistical methods, including spatiotemporal Gaussian process regression, the Cause of Death Ensemble Model (CODEm), and Bayesian meta-regression (DisMod-MR) [24].

Burden Description

The CKD-HF disease burden, including prevalence and years lived with disability (YLDs), was extracted from the GBD 2021. Metrics were reported as absolute counts, rates per 100,000 population (all-age and age-specific), and age-standardized rates (ASR) on the basis of the GBD standard population structure. The age-standardized prevalence rates (ASPR) and age-standardized YLDs rates (ASYR) were derived by weighting population-specific rates according to the age structure of the World Standard Population 2021, as defined by the WHO. This standardization mitigates the influence of age distribution differences, ensuring the comparability of disease burden estimates across regions and periods. All estimates from the GBD study are reported with 95% uncertainty intervals (UIs), which were calculated by taking 1,000 posterior distribution samples and using the 2.5th and 97.5th ordered values of the uncertainty distribution.

In the GBD study, HF was stratified into four severity levels – treated, mild, moderate, and severe – with disability weights ranging from 0 (full health) to 1 (death). YLDs were calculated by multiplying the prevalence of CKD-HF at each severity level and its corresponding disability weight [23]. The sociodemographic index (SDI) quantifies the socioeconomic status of a country, which is calculated as the geometric mean of the fertility rate in women under 25 years of age, the mean years of education in individuals aged 15 years and older, and lag-distributed income per capita. On the basis of the SDI scale from 0 to 1, countries are categorized into five quintiles: low-, low-middle-, middle-, high-middle-, and high-SDI.

Descriptive Analysis

To comprehensively assess the disease burden of CKD-HF comprehensively, descriptive analyses were conducted globally across 5 SDI regions, 21 GBD regions, and 204 countries. The CKD-HF incidence rates and YLDs (cases and ASR) were compared globally by sex, SDI, and GBD region from 1990 to 2021, with data from 204 countries visualized on a world map. The distributions of potential causes of CKD-HF across years, age groups, and SDI regions are illustrated in stacked bar charts.

Trend Analysis

The estimated annual percentage change (EAPC) was calculated by fitting a linear regression model to the natural logarithm of the ASPR and ASYR to the corresponding years, enabling the assessment of trends in the disease burden of CKD-HF from 1990 to 2021 [25]. An increasing trend is defined when the EAPC and the lower boundary of its 95% confidence interval (CI) exceed 0, whereas a decreasing trend occurs when both the EAPC and the upper boundary are below 0. A stable trend is considered if the 95% CI encompasses 0.

Cross-Country Health Inequality Analysis

The slope index of inequality (SII) and concentration index were used to assess absolute and relative health inequalities in CKD-HF burden across socioeconomic groups (https://www.who.int/publications/i/item/9789241548632). The SII is derived by regressing age-standardized disease rates on the weighted relative rank of countries based on the SDI, with the regression slope representing health disparities between the lowest and highest SDI groups. The Lorenz curve was generated by fitting a cubic spline function to the cumulative proportion of the ASPR or ASYR against the cumulative population ranked by the SDI. The concentration index was then obtained through numerical integration of the area under the Lorenz curve, which was calculated as twice the area between the Lorenz curve and the diagonal line. A positive concentration index, with the Lorenz curve below the diagonal, indicates a greater disease burden in high-SDI regions, whereas a negative concentration index, with the Lorenz curve above the diagonal, suggests a greater burden in low-SDI regions. Health inequality monitoring provides an evidence-based foundation for health planning to reduce disparities in the distribution of the CKD-HF burden.

Predictive Analysis

An autoregressive integrated moving average (ARIMA) model was applied to project trends in the CKD-HF burden through 2040 [26]. The ARIMA model converts nonstationary time series into a stationary form through differencing, followed by modeling and forecasting using autoregressive (AR) and moving average (MA) components. The ARIMA model parameters – p (order of the AR), d (degree of differencing), and q (order of the MA) – are determined on the basis of optimization criteria such as the Akaike information criterion and Bayesian information criterion. An optimally fitted predictive model increases the understanding of disease progression trends, offering valuable evidence for informing prevention and treatment strategies.

Data Processing and Visualization

All the statistical analyses were conducted using R (version 4.3.3) and RStudio, with data manipulation and analysis with the data.table, dplyr, devtools, reshape, tidyr, and tidyverse packages, and data visualization was performed with the ggplot2 and ggmap packages. A two-sided p value ≤0.05 was considered to indicate statistical significance.

Results

The CKD-HF Burden Increased Globally, with Wide Regional and SDI Disparities from 1990 to 2021

The global burden of CKD-HF increased from 1990 to 2021. Globally, the prevalence of CKD-HF rose from 617,817 cases (95% UI: 505,140–746,539) in 1990 to 1,936,886 cases (95% UI: 1,600,208–2,334,467) in 2021, and the ASPR increased from 13.58 per 100,000 population (95% UI: 11.16–16.22) to 24.21 (95% UI: 19.86–29.23), with an EAPC of 2.04 (95% CI: 1.96–2.11) (shown in Table 1). Similarly, the number of YLDs rose from 79,090 years (95% UI: 50,942–114,997) to 245,658 (95% UI: 154,573–356,658), and the ASYR increased from 1.73 (95% UI: 1.12–2.56) to 3.07 (95% UI: 1.95–4.44), corresponding to an EAPC of 2.02 (95% CI: 1.95–2.10) (shown in Table 1).

Table 1.

The global and regional burden change of CKD-HF from 1990 to 2021

Characteristics	Prevalence					YLDs
	number in 1990 (95% UI)	number in 2021 (95% UI)	ASR in 1990 (95% UI)	ASR in 2021 (95% UI)	EAPC (95% CI)	number in 1990 (95% UI)	number in 2021 (95% UI)	ASR in 1990 (95% UI)	ASR in 2021 (95% UI)	EAPC (95% CI)
Global	617,817 (505,140–746,539)	1,936,886 (1,600,208–2,343,467)	13.58 (11.16–16.22)	24.21 (19.86–29.23)	2.04 (1.96–2.11)	79,009 (50,942–114,997)	245,658 (154,573–356,658)	1.73 (1.12–2.56)	3.07 (1.95–4.44)	2.02 (1.95–2.10)
Sex
Male	329,633 (267,964–397,837)	979,935 (800,987–1,189,465)	15.66 (12.74–18.75)	26.58 (21.56–32.13)	1.84 (1.78–1.91)	42,137 (27,119–61,251)	124,392 (78,959–181,885)	1.98 (1.3–2.95)	3.37 (2.14–4.92)	1.84 (1.77–1.90)
Female	288,184 (237,388–345,335)	956,951 (788,967–1,164,170)	12.05 (10.01–14.33)	22.27 (18.47–26.76)	2.18 (2.09–2.27)	36,873 (23,866–53,610)	121,266 (76,603–176,762)	1.54 (1.20–2.60)	2.83 (1.80–4.07)	2.16 (2.07–2.25)
SDI
High-SDI	92,092 (73,603–114,811)	430,794 (328,466–544,755)	9.36 (7.67–11.31)	22.16 (17.83–27.14)	3.22 (3.07–3.37)	13,263 (8,050–19,272)	36,718 (22,152–54,094)	3.86 (2.42–5.86)	4.85 (3.04–7.25)	3.18 (3.03–3.33)
High-middle SDI	81,636 (67,498–97,480)	245,176 (198,767–307,405)	8.53 (7.08–10.19)	15.08 (12.60–18.41)	2.06 (1.97–2.16)	11,784 (7,490–17,611)	54,273 (33,919–81,384)	1.20 (0.77–1.76)	2.81 (1.76–4.17)	2.04 (1.96–2.13)
Middle-SDI	205,476 (169,145–243,981)	614,414 (503,757–751,650)	16.16 (13.47–19.38)	25.50 (21.01–30.55)	1.60 (1.50–1.69)	10,493 (6,813–15,180)	31,161 (19,643–46,635)	1.09 (0.71–1.59)	1.92 (1.22–2.83)	1.59 (1.50–1.69)
Low-middle SDI	133,714 (109,026–163,123)	356,426 (286,218–427,796)	15.82 (13.00–18.96)	22.84 (18.63–27.44)	1.16 (1.11–1.20)	26,318 (17,168–38,013)	77,948 (48,711–112,919)	2.05 (1.33–3.01)	3.23 (2.04–4.69)	1.17 (1.12–1.21)
Low-SDI	104,328 (79,510–132,906)	288,640 (219,809–361,997)	30.88 (23.91–39.75)	38.71 (30.16–49.45)	0.74 (0.68–0.81)	17,078 (10,998–24,593)	45,376 (28,936–65,612)	2.00 (1.31–2.95)	2.89 (1.85–4.21)	0.75 (0.68–0.82)
Location
Australasia	1,893 (1,465–2,467)	10,602 (8,124–14,019)	8.67 (6.80–11.13)	20.48 (16.39–26.03)	3.49 (3.23–3.74)	11,572 (7,167–16,885)	31,859 (19,396–46,218)	9.32 (5.84–13.95)	11.23 (7.00–16.78)	3.46 (3.21–3.72)
Western Europe	37,117 (28,792–47,017)	158,749 (117,367–205,860)	7.44 (6.01–9.11)	17.73 (14.14–21.92)	3.49 (3.24–3.74)	2,095 (1,338–3,030)	6,653 (4,158–10,221)	1.73 (1.12–2.49)	2.81 (1.77–4.28)	3.47 (3.22–3.71)
High income	18,336 (13,965–23,122)	83,018 (59,129–108,038)	10.57 (8.17–13.02)	17.99 (14.27–22.11)	1.64 (1.46–1.82)	5,769 (3,326–8,722)	15,593 (9,067–23,394)	4.49 (2.69–7.08)	6.08 (3.69–9.31)	1.62 (1.44–1.80)
Asia Pacific
High income	29,279 (22,591–37,823)	162,449 (120,097–217,695)	8.81 (6.94–10.99)	26.34 (20.59–34.18)	4.15 (3.99–4.31)	9,533 (6,120–13,742)	25,049 (15,593–36,369)	1.18 (0.77–1.74)	1.63 (1.02–2.38)	4.09 (3.94–4.25)
North America
Southern Latin America	6,785 (5,474–8,325)	18,109 (13,246–23,402)	14.58 (11.60–17.76)	22.34 (16.87–28.23)	1.45 (1.21–1.69)	3,758 (2,350–5,632)	20,496 (12,460–32,128)	1.13 (0.72–1.67)	3.34 (2.04–5.08)	1.43 (1.20–1.67)
Central Europe	12,865 (10,520–15,504)	18,346 (14,776–23,211)	10.73 (8.75–13.02)	12.69 (10.26–15.35)	0.59 (0.43–0.75)	1,595 (928–2,343)	3,431 (2051–5,180)	4.26 (2.59–6.54)	5.81 (3.51–8.88)	0.58 (0.42–0.73)
Eastern Europe	11,201 (8,803–14,126)	13,265 (10,102–17,575)	5.46 (4.17–7.07)	6.04 (4.50–7.80)	0.37 (−0.28–1.01)	241 (149–361)	1,335 (824–1,996)	1.10 (0.68–1.64)	2.59 (1.62–3.83)	0.37 (0.28–1.01)
Central Asia	4,272 (3,349–5,485)	10,020 (7,952–12,443)	5.80 (4.60–7.31)	11.44 (9.09–14.22)	2.14 (1.74–2.54)	626 (412–899)	1,887 (1,210–2,778)	2.05 (1.33–2.93)	3.73 (2.44–5.46)	2.14 (1.74–2.53)
Caribbean	4,898 (4,069–5,924)	14,919 (12,167–18,230)	16.08 (13.36–19.29)	29.45 (23.97–35.91)	2.29 (2.14–2.43)	36 (22–52)	113 (72–168)	0.92 (0.58–1.37)	1.39 (0.86–2.07)	2.27 (2.12–2.41)
Tropical Latin America	16,301 (13,055–19,827)	52,812 (41,264–67,766)	13.54 (11.00–16.30)	22.31 (17.70–28.23)	1.72 (1.66–1.78)	1,187 (787–1,685)	4,681 (2,940–6,669)	4.30 (2.74–6.08)	7.87 (4.90–11.24)	1.67 (1.62–1.73)
Central Latin America	40,403 (33,342–48,288)	136,673 (112,319–166,891)	31.84 (26.90–37.67)	55.34 (45.71–67.88)	2.10 (1.74–2.47)	552 (353–809)	1,293 (844–1,841)	0.75 (0.48–1.09)	1.48 (0.96–2.13)	2.09 (1.72–2.45)
Andean Latin America	9,329 (7,698–11,201)	37,105 (29,981–44,830)	34.10 (28.14–41.05)	62.49 (50.13–75.79)	2.03 (1.73–2.34)	5,168 (3,338–7,293)	17,298 (10,921–25,008)	4.04 (2.64–5.86)	7.00 (4.40–10.25)	2.03 (1.73–2.33)
North Africa and Middle East	41,227 (34,785–49,402)	137,122 (115,665–162,021)	17.31 (14.55–20.68)	28.31 (23.70–34.10)	1.78 (1.72–1.84)	1,868 (1,100–2,822)	5,274 (3,115–8,100)	5.15 (3.12–8.01)	6.09 (3.78–9.26)	1.77 (1.71–1.83)
South Asia	74,156 (60,171–90,668)	195,748 (156,676–239,124)	9.28 (7.62–11.09)	12.80 (10.31–15.63)	0.95 (0.90–1.00)	5,278 (3,505–7,572)	17,456 (11,393–24,690)	2.19 (1.42–3.11)	3.58 (2.28–5.12)	0.95 (0.90–1.00)
Oceania	277 (223–348)	885 (713–1,088)	7.25 (5.90–9.04)	10.97 (8.75–14.16)	1.28 (1.20–1.35)	868 (547–1,264)	2,289 (1,394–3,473)	1.86 (1.17–2.70)	2.83 (1.71–4.21)	1.26 (1.19–1.33)
East Asia	80,847 (65,583–99,268)	269,533 (209,708–357,445)	8.85 (7.19–11.08)	14.10 (11.33–18.00)	1.62 (1.54–1.70)	1,447 (911–2,116)	1,713 (1,028–2,647)	0.70 (0.44–1.03)	0.78 (0.47–1.18)	1.60 (1.52–1.68)
Southeast Asia	64,418 (52,711–77,652)	174,881 (145,860–209,021)	17.77 (14.79–21.09)	29.48 (24.28–35.47)	1.72 (1.65–1.79)	1,658 (1,066–2,424)	2,349 (1,447–3,552)	1.38 (0.88–1.98)	1.63 (1.04–2.38)	1.70 (1.63–1.77)
Eastern sub-Saharan	45,315 (33,703–59,867)	122,524 (91,471–155,705)	35.99 (27.05–48.95)	48.69 (36.91–65.67)	1.03 (1.01–1.05)	10,417 (6,685–15,202)	34,358 (20,992–51,769)	1.13 (0.72–1.67)	1.80 (1.11–2.65)	1.03 (1.01–1.05)
Africa
Western sub-Saharan Africa	91,749 (69,705–113,369)	251,736 (192,601–310,999)	75.11 (57.97–94.64)	90.21 (69.91–113.99)	0.50 (0.43–0.58)	4,730 (2,960–7,213)	19,938 (12,736–29,970)	0.95 (0.61–1.40)	2.25 (1.43–3.35)	0.51 (0.44–0.59)
Central sub-Saharan	14,630 (10,545–19,347)	41,347 (29,931–53,503)	41.09 (30.18–53.25)	48.51 (36.25–64.04)	0.52 (0.46–0.57)	8,262 (5,452–11,823)	22,155 (14,215–31,461)	2.26 (1.46–3.25)	3.71 (2.37–5.35)	0.52 (0.46–0.58)
Africa
Southern sub-Saharan Africa	12,520 (9,518–15,728)	27,043 (20,942–34,101)	33.86 (26.16–44.31)	46.20 (35.75–60.46)	0.93 (0.83–1.03)	2,349 (1,462–3,450)	10,439 (6,425–15,869)	1.35 (0.85–1.98)	2.29 (1.46–3.31)	0.93 (0.83–1.03)

YLDs, years lived with disability; ASR, age-standardized rate; EAPC, estimated annual percentage change; SDI, sociodemographic index; GBD, global burden of disease.

Trends varied across SDI regions. High-SDI regions experienced the most rapid relative growth, with the ASPR increasing from 9.36 (95% UI: 7.67–11.31) to 22.16 (95% UI: 17.83–27.14) and an EAPC of 3.22 (95% CI: 3.07–3.37) (shown in Table 1). The ASYR in high-SDI regions increased from 3.86 (95% UI: 2.42–5.86) to 4.85 (95% UI: 3.04–7.25), with an EAPC of 3.18 (95% CI: 3.03–3.33) (shown in Table 1). Although low-SDI regions exhibited the slowest growth in CKD-HF burden, reflected by EAPCs of 0.75 (95% CI: 0.68–0.81) for ASPR and 0.74 (95% CI: 0.68–0.82) for ASYR, these regions consistently maintained the highest ASPR across all SDI categories, increasing from 30.88 (95% UI: 23.91–39.75) in 1990 to 38.71 (95% UI: 30.16–49.45) in 2021 (shown in Table 1). Middle-SDI regions consistently had the highest absolute prevalence, increasing from 205,476 (95% UI: 169,145–243,981) in 1990 to 614,414 (95% UI: 503,757–751,650) in 2021 (shown in Table 1).

Across GBD regions, Western Sub-Saharan Africa had the highest ASPR (90.21; 95% UI: 69.91–113.99) of CKD-HF in 2021, followed by Andean Latin America (62.49; 95% UI: 50.13–75.79) and Central Latin America (55.34; 95% UI: 45.71–67.88) (shown in Table 1). In comparison, Eastern Europe reported the lowest ASPR (6.04; 95% UI: 4.50–7.80) in 2021 and was the only region without a clear upward trend (shown in Table 1). The highest ASYRs of CKD-HF in 2021 were observed in Australasia (11.23; 95% UI: 7.00–16.78), Tropical Latin America (7.87; 95% UI: 4.90–11.24), and Andean Latin America (7.00; 95% UI: 4.40–10.25), whereas the lowest ASYR was observed in East Asia (0.78; 95% UI: 0.47–1.18) (shown in Table 1). From 1990 to 2021, the most pronounced increase was observed in high-income North America, with an EAPC of 4.15 (95% CI: 3.99–4.31) for the ASPR and 4.09 (95% CI: 3.94–4.25) for the ASYR (shown in Table 1).

At the national level, the burden of CKD-HF has shown a sustained upward trend in most countries, with the most pronounced increases observed in Ukraine, Armenia, Denmark, Norway, and Germany (shown in Fig. 1c). These countries reported EAPCs ranging from 5.15 to 12.48 for the ASPR and from 5.11 to 12.48 for the ASYR. In contrast, Poland and the Russian Federation were the only countries to report a decline in the CKD-HF burden, with EAPCs for the ASPR ranging from −0.44 to −0.09 (shown in Fig. 1c) and those for the ASYR ranging from −0.45 to −0.08 (shown in Fig. 2c). China, Nigeria, the USA, India, and Mexico accounted for the highest number of CKD-HF cases globally in 2021, with prevalences ranging from 88,404 to 250,047 cases (shown in Fig. 1 a) and YLDs ranging from 11,187 to 31,906 years (shown in Fig. 2a). Nigeria exhibited an exceptionally high disease burden in 2021, with an ASPR (140.12; 95% UI: 109.42–175.70) (shown in Fig. 1b) and an ASYR (17.42; 95% UI: 10.84–25.75) (shown in Fig. 2b), exceeding those of all other countries. El Salvador, Nicaragua, Guatemala, and Mexico ranked behind Nigeria, with ASPRs ranging from 70.70 to 88.48 per 100,000 population (shown in Fig. 1b) and ASYRs ranging from 8.93 to 11.17 per 100,000 population (shown in Fig. 2b). Despite experiencing the fastest increases in both the ASPR and ASYR, Ukraine maintained the lowest CKD-HF burden among all countries in 2021, with an ASPR of 3.27 (95% UI: 2.30–4.51) (shown in Fig. 1b) and an ASYR of 0.42 (95% UI: 0.25–0.66) (shown in Fig. 2b). Additionally, Belarus and Iceland presented relatively low disease burdens, with an ASPR of 3–5 per 100,000 population (shown in Fig. 1b) and an ASYR of 0.54–0.64 per 100,000 population (shown in Fig. 2b) in 2021.

Fig. 1.

Geographical distribution of the prevalence of CKD-HF. a The geographical distribution of prevalence numbers in 2021: China, Nigeria, the USA, and India accounted for the highest number of CKD-HF cases globally, with the prevalence ranging from 133,759 to 250,047 cases. b The geographical distribution of the ASPR in 2021: Nigeria, El Salvador, Nicaragua, Guatemala, and Mexico presented the highest ASPRs, ranging from 70.70 to 140.12 per 100,000. c The geographical distribution of the EAPC of the ASPR from 1990 to 2021: the ASPR of CKD-HF showed a sustained upward trend in most countries, with the most pronounced increases observed in Ukraine, Armenia, Denmark, Norway, and Germany. Only Poland and the Russian Federation demonstrated a downward trend. CKD-HF, heart failure attributable to chronic kidney disease; ASPR, age-standardized prevalence rate; EAPC, estimated annual percentage change.

Fig. 2.

Geographical distribution of the YLDs of CKD-HF. a The geographical distribution of YLD numbers in 2021: China, Nigeria, the USA, and India accounted for the highest number of CKD-HF cases globally, with YLDs ranging from 17,117 to 31,906 years. b The geographical distribution of the ASYR in 2021: Nigeria, El Salvador, Nicaragua, Guatemala, and Mexico presented the highest ASYR, ranging from 8.93 to 17.42 per 100,000. c The geographical distribution of the EAPC in the ASYR from 1990 to 2021: the ASYR of CKD-HF showed a sustained upward trend in most countries, with the most pronounced increases observed in Ukraine, Armenia, Denmark, Norway and Germany. Only Poland and the Russian Federation demonstrated a downward trend. YLDs, years lived with disability; CKD-HF, heart failure attributable to chronic kidney disease; ASYR, age-standardized YLD rate; EAPC, estimated annual percentage change.

The Burden of CKD-HF Peaked in Early Childhood and Late Old Age, with a Greater Disease Burden Observed in Males

Throughout the study period, females consistently presented a lower CKD-HF burden than males. Among females, the prevalence increased from 288,184 (95% UI: 237,388–345,335) in 1990 to 956,951 (95% UI: 788,967–1,164,170) in 2021; the ASPR rose from 12.05 (95% UI: 10.01–14.33) to 22.27 (95% UI: 18.47–26.76), with an EAPC of 2.18 (95% CI: 2.09–2.27) (shown in Table 1). The prevalence among males increased from 329,633 (95% UI: 267,964–397,837) in 1990 to 979,935 (95% UI: 800,987–1,189,465) in 2021, and the ASPR rose from 15.66 (95% UI: 12.74–18.75) to 26.58 (95% UI: 21.56–32.13), with an EAPC of 1.84 (95% CI: 1.78–1.91) (shown in Table 1). Similarly, both sexes experienced a rising trend in YLDs. Among females, YLDs increased from 36,873 (95% UI: 23,866–53,610) in 1990 to 121,266 (95% UI: 76,603–176,762) in 2021; the ASYR rose from 1.54 (95% UI: 1.20–2.60) to 2.83 (95% UI: 1.80–4.07), with an EAPC of 2.16 (95% CI: 2.07–2.25) (shown in Table 1). The YLDs among males increased from 42,137 (95% UI: 27,119–61,251) to 124,392 (95% UI: 78,959–181,885), with the ASYR increasing from 1.98 (95% UI: 1.32–2.95) to 3.37 (95% UI: 2.14–4.92) and an EAPC of 1.84 (95% CI: 1.77–1.90) (shown in Table 1).

The age-specific distribution of CKD-HF was similar between males and females, suggesting a consistent pattern across sexes. The number of CKD-HF cases in 2021 reached a nadir at 40–44 years and peaked at 70–74 years in both sexes (shown in Fig. 3). In the 40–44-year age group, females had a prevalence of CKD-HF of 17,582 (95% UI: 9,479–28,741) and 2,269 YLDs (95% UI: 1,148–4,090), and males had a CKD-HF prevalence of 15,576 (95% UI: 8,461–26,032) and 2,009 YLDs (95% UI: 1,004–3,618). Among individuals aged 70–74 years, females had a CKD-HF prevalence of 121,290 (95% UI: 73,365–192,760) and 15,342 YLDs (95% UI: 8,237–26,461), and males had a CKD-HF prevalence of 117,852 (95% UI: 71,097–189,580) and 14,921 YLDs (95% UI: 7,935–26,309). Notably, children aged 0–5 years presented the highest burden of CKD-HF among the population under age 65. Within this age group, females had a prevalence of 58,026 (95% UI: 37,949–85,870) and 7,445 YLDs (95% UI: 4,167–12,194), whereas males had a higher prevalence of 93,828 (95% UI: 62,601–136,026) and 11,984 YLDs (95% UI: 6,815–19,434). The ASPR and ASYR of CKD-HF in 2021 reached a nadir at ages 30–34 years and peaked at age 95+ years in both sexes. In the 30–34-year age group, females had an ASPR of 6.24 (95% UI: 3.39–9.99) and an ASYR of 0.80 (95% UI: 0.42–1.40), and males had an ASPR of 5.30 (95% UI: 2.90–8.55) and an ASYR of 0.68 (95% UI: 0.35–1.20). Among individuals aged 95+ years, females had an ASPR of 555.33 (95% UI: 274.40–988.75) and an ASYR of 67.10 (95% UI: 31.66–129.32), and males had an ASPR of 752.40 (95% UI: 366.97–1,344.60) and an ASYR of 90.51 (95% UI: 40.80–170.53). Similarly, children aged 0–5 years had the highest ASPR and ASYR of CKD-HF among individuals under age 60 years in 2021. Within this age group, females had an ASPR of 18.24 (95% UI: 11.93–26.99) and an ASYR of 2.34 (95% UI: 1.31–3.83), whereas males had a higher ASPR of 27.60 (95% UI: 18.41–40.01) and an ASYR of 3.53 (95% UI: 2.00–5.72).

Fig. 3.

Sex- and age-specific distributions and trends in the burden of CKD-HF. a From 1990 to 2021, the prevalence number and rate of CKD-HF steadily increased in both sexes, with males consistently bearing a greater burden than females. b From 1990 to 2021, the number and rate of YLDs for CKD-HF steadily increased in both sexes, with males consistently bearing a greater burden than females. c In 2021, CKD-HF predominantly affected children and elderly individuals, with the highest number of cases observed in the 70–74-year age group. Among individuals under 30 years of age, males had more cases, whereas females surpassed males in those over 30 years of age. d In 2021, the ASPR of CKD-HF followed a U-shaped distribution across age groups, with the highest ASPR observed in the 95+ year age group and the lowest in the 30–34-year age group. e In 2021, the burden of YLDs for CKD-HF was most pronounced in children and elderly individuals, with the highest number of YLDs observed in the 70–74-year age group. Among those under 30 years, males had a greater burden, whereas females surpassed males in those over 30 years. f In 2021, the ASYR of CKD-HF followed a U-shaped distribution across age groups, with the highest ASYR observed in the 95+ year age group and the lowest in the 30–34-year age group. CKD-HF, heart failure attributable to chronic kidney disease; YLDs, years lived with disability; ASPR, age-standardized prevalence rate; ASYR, age-standardized YLD rate; EAPC, estimated annual percentage change.

CKD Attributable to Other and Unspecified Causes Remained the Main Driver of CKD-HF, with Increasing Contributions from Diabetic Nephropathy and Hypertensive Nephropathy

The distribution of CKD-HF etiology varied across years, age groups, and SDI regions. From 1990 to 2021, CKD attributable to other and unspecified causes remained the primary contributor to CKD-HF, although its proportion steadily declined from 64.41% in 1990 to 55.59% in 2021 (shown in Fig. 4a). The contribution of glomerulonephritis-related kidney disease also decreased, from 12.03% in 1990 to 9.19% in 2021 (shown in Fig. 4a). In contrast, the contributions of type 2 diabetic nephropathy and hypertensive nephropathy steadily increased, with that of type 2 diabetic nephropathy increasing from 14.20% in 1990 to 19.40% in 2021 and that of hypertensive nephropathy increasing from 11.55% to 14.92% (shown in Fig. 4a). The contribution of type 1 diabetic nephropathy to CKD-HF has remained consistently low over the past 32 years, ranging from 0.78% to 0.94% (shown in Fig. 4a).

Fig. 4.

Proportional contribution of etiologies to CKD-HF across year, age group and SDI regions. a From 1990 to 2021, the contribution of CKD-HF due to other and unspecified causes, along with glomerulonephritis, gradually decreased, whereas the contributions from type 2 diabetic nephropathy and hypertensive nephropathy steadily increased. b The contribution of CKD due to other and unspecified causes to CKD-HF followed a U-shaped pattern across age groups, whereas the contribution of type 2 diabetic nephropathy showed an inverted U-shaped distribution. The contribution of hypertensive nephropathy increased with age, and glomerulonephritis was the second leading cause of CKD-HF in those under 50 years of age. c With increasing SDI, the contribution of CKD due to other or unspecified causes and glomerulonephritis to CKD-HF decreased, whereas the contributions of type 2 diabetic nephropathy and hypertensive nephropathy increased. CKD-HF, heart failure attributable to chronic kidney disease; SDI, sociodemographic index.

A U-shaped pattern was observed in the contribution of CKD due to other and unspecified causes to CKD-HF across age groups in 2021, with the highest contributions in children aged 0–4 years (88.21%) and elderly individuals aged 95+ years (86.00%) and the lowest in individuals aged 60–64 years (37.44%) (shown in Fig. 4b). In contrast, type 2 diabetic nephropathy-related HF had an inverted U-shaped distribution, peaking at 36.98% in individuals aged 65–69 years, with no cases in children under 14 years. The prevalence of hypertensive nephropathy-related HF increased with age, peaking at 21.39% in individuals aged 65–69 years (shown in Fig. 4b). Chronic glomerulonephritis was the second leading cause of CKD-HF in individuals under 50 years of age, with the highest contribution in individuals aged 30–34 years (24.98%) (shown in Fig. 4b). Type 1 diabetic nephropathy contributed less than 3.5% to CKD-HF across age groups, with the highest prevalence in individuals aged 35–55 years (shown in Fig. 4b).

Etiological analysis based on SDI regions revealed that CKD due to other and unspecified causes was the leading cause of CKD-HF worldwide in 2021, with the highest proportion in low-SDI regions (65.73%) and the lowest in high-middle-SDI regions (51.03%) (shown in Fig. 4c). Type 2 diabetic nephropathy ranked as the second leading cause of CKD-HF across all regions except low-SDI regions, peaking at 23.56% in high-middle-SDI regions compared with 10.70% in low-SDI regions (shown in Fig. 4c). Chronic glomerulonephritis was the second leading cause of CKD-HF in low-SDI regions, contributing 12.86% to the burden (shown in Fig. 4c). From 1990 to 2021, the contribution of hypertensive nephropathy to CKD-HF increased across all SDI regions, with the largest increase observed in middle-SDI regions (from 11.34% to 15.64%) (shown in Fig. 4c). Similarly, the contribution of type 2 diabetic nephropathy increased, with the greatest increase observed in middle-SDI regions (from 13.26% to 21.47%) (shown in Fig. 4c).

Despite a Narrowing Health Gap in CKD-HF, Low-SDI Countries Continued to Bear a Disproportionately Greater Burden

While the gap in CKD-HF has narrowed, health inequalities persist across SDI regions, with low-SDI countries shouldering a disproportionately greater burden. The SII showed a narrowing absolute gap in the ASPR between the highest and lowest SDI countries, decreasing from −26.09 (95% CI: −29.95 to −22.24) in 1990 to −20.45 (95% CI: −27.21 to −13.69) in 2021 (shown in Fig. 5a). A similar trend was observed in the ASYR, with the gap narrowing from −3.24 (95% CI: −3.72 to −2.75) to −2.53 (95% CI: −3.37 to −1.68) (shown in Fig. 5b). Despite this decline, the consistently negative SII over the 3 decades reflects persistent disparities in the CKD-HF burden between wealthier and low socioeconomic status countries. In terms of relative inequality, the concentration index for the ASPR rose from −0.25 in 1990 to −0.14 in 2021 (shown in Fig. 5c), and that for ASYR rose from −0.18 to 0.02 (shown in Fig. 5d), indicating a notable reduction in relative inequality. The Lorenz curves for ASPR and ASYR intersected the equality line in both 1990 and 2021, with most curves positioned above the line, further indicating a disproportionate burden in low-SDI countries.

Fig. 5.

Health inequality analysis in CKD-HF across SDI regions. a The SII of the ASPR increased from −26.09 (95% CI: −29.95 to −22.24) in 1990 to −20.45 (95% CI: −27.21 to −13.69) in 2021. b The SII of ASYR increased from −3.24 (95% CI: −3.72 to −2.75) in 1990 to −2.53 (95% CI: −3.37 to −1.68) in 2021. c The concentration index of ASPR increased from −0.25 in 1990 to −0.14 in 2021. d The concentration index of the ASYR rose from −0.18 in 1990 to 0.02 in 2021. e The SII of ASPR remained negative from 1990 to 2021, despite showing a gradual increase over time. f The SII of the ASYR remained negative from 1990 to 2021, despite showing a gradual increase over time. CKD-HF, heart failure attributable to chronic kidney disease; SDI, sociodemographic index; SII, slope index of inequality; CI, confidence interval; ASPR, age-standardized prevalence rate; ASYR, age-standardized YLD rate.

The Global CKD-HF Burden Is Expected to Continue to Rise, with a Higher Proportion in Underdeveloped Regions

The ARIMA model, with a strong goodness of fit, was used to predict CKD-HF prevalence and YLDs trends through 2040. Projections indicate a continued global increase in both the prevalence and YLDs from 2022 to 2040. The global ASPR is expected to increase from 24.70 (95% CI: 24.54–24.86) in 2022 to 30.90 (95% CI: 29.62–32.18) in 2040 (shown in Fig. 6a), and the ASYR is projected to increase from 3.11 (95% CI: 3.09–3.13) to 3.84 (95% CI: 3.59–4.08) (shown in Fig. 6b). An increasing trend in prevalence and YLDs was observed in both sexes from 1990 to 2021, and this trend is expected to continue through 2040. The ASPR for CKD-HF in females is projected to increase from 22.59 (95% CI: 22.44–22.74) in 2022 to 28.74 (95% CI: 27.24–30.23) in 2040 (shown in Fig. 6a), with the ASYR increasing from 2.85 (95% CI: 2.83–2.87) to 3.49 (95% CI: 3.17–3.80) (shown in Fig. 6b). In males, the ASPR is expected to increase from 27.13 (95% CI: 26.95–27.30) to 33.53 (95% CI: 32.24–34.82) (shown in Fig. 6a), with the ASYR increasing from 3.42 (95% CI: 3.39–3.44) to 4.22 (95% CI: 4.02–4.41) (shown in Fig. 6b).

Fig. 6.

ARIMA predictions of the burden of CKD-HF worldwide, across different sexes and SDI regions. a By 2040, the global ASPR is expected to increase to 30.90 (95% CI: 29.62–32.18), with males maintaining a greater burden. b By 2040, the global ASYR is expected to increase to 3.84 (95% CI: 3.59–4.08), with males maintaining a greater burden. c By 2040, an upward trend in ASPR is projected across all SDI regions, with low-SDI regions continuing to bear the highest burden. d By 2040, an increasing trend in the ASYR is projected across all SDI regions, with low-SDI regions continuing to bear the highest burden. ARIMA, autoregressive integrated moving average; CKD-HF, heart failure attributable to chronic kidney disease; SDI, sociodemographic index; ASPR, age-standardized prevalence rate; CI, confidence interval; ASYR, age-standardized YLD rate.

Projected trends indicate that from 2022 to 2040, the CKD-HF burden will rise across all SDI regions except for low-SDI regions, where a decline is expected. By 2040, the ASPR in low-SDI regions is projected to decrease from 38.61 (95% CI: 38.51–38.71) in 2022 to 33.32 (95% CI: 18.23–48.42), and the ASYR is expected to decrease from 4.83 (95% CI: 4.82–4.85) to 4.56 (95% CI: 3.04–6.07) (shown in Fig. 6c). The high-middle-SDI region is predicted to maintain the lowest burden, with the ASPR increasing from 15.30 (95% CI: 15.18–15.43) in 2022 to 19.00 (95% CI: 17.26–27.73) by 2040 (shown in Fig. 6c), and the ASYR increasing from 1.95 (95% CI: 1.93–1.97) to 2.42 (95% CI: 2.20–2.64) (shown in Fig. 6d). The ASPR in high-SDI regions is expected to increase slowly, from 22.19 (95% CI: 21.92–22.47) in 2022 to 22.50 (95% CI: 13.46–31.56) (shown in Fig. 6c), with the ASYR rising from 2.83 (95% CI: 2.79–2.86) to 3.51 (95% CI: 2.91–4.12) (shown in Fig. 6d). Despite this decline, low-SDI regions will continue to have the highest ASPR and ASYR, and the burden in underdeveloped regions is projected to remain higher than that in developed regions in 2040 (shown in Fig. 6c, d).

Discussion

Rising Global Burden of CKD-HF

In the present study, we comprehensively assessed the global, regional, and national burdens of CKD-HF from 1990 to 2021. Our findings demonstrated that the global burden of CKD-HF has risen substantially over the past 3 decades, with the number of prevalent cases more than tripling from 0.62 million in 1990 to 1.94 million in 2021. Concurrently, the increase in the ASPR and ASYR indicated that the increased burden is not merely attributable to demographic growth. This upward trend is projected to continue through 2040 on the basis of ARIMA modeling. Nevertheless, improved diagnostics and growing clinical awareness of cardiorenal syndromes may have partially contributed to the observed rise in prevalence. Importantly, the consistent increases in the ASPR and ASYR, even in regions with limited diagnostic infrastructure, suggest that enhanced detection alone cannot fully account for the magnitude of the increase. In previous global analyses, CKD-HF was not disaggregated from overall HF trends, potentially underestimating its rising public health impact, an issue that was directly addressed in this study [27, 28]. These findings may help inform future GBD updates, improve the understanding of CKD-HF epidemiology, and support more effective planning of resources and interventions.

Sex-Specific Disparities in CKD-HF Burden

Our study revealed a consistent upward trend in the burden of CKD-HF across both sexes, with males persistently exhibiting a greater burden than females from 1990 to 2021 – a disparity projected to continue through 2040. Sex-specific differences in the burden of CKD-HF are likely driven by a combination of biological and behavioral mechanisms [29, 30]. Biologically, men with CKD are more prone to cardiac remodeling, systemic inflammation, and faster progression to HF with decreased ejection fraction, which is partly due to hormonal influences, endothelial dysfunction, and neurohormonal differences [31–33]. In contrast, women – particularly after menopause – are more susceptible to HF with preserved ejection fraction, which is associated with increased vascular stiffness, altered myocardial energetics, and a decline in the cardioprotective effects of estrogen [34, 35]. Behavioral and healthcare access factors may further contribute to these disparities. Men more frequently engage in high-risk behaviors such as smoking and poor dietary patterns [36], whereas women are more likely to experience delayed CKD diagnosis, reduced referral to nephrology care, and underuse of guideline-recommended therapies [37]. Tailored strategies that integrate biological sex- and sex-informed care models are essential to address the evolving global burden equally.

Age-Related Patterns and Vulnerabilities

The burden of CKD-HF followed a bimodal age pattern, reaching its lowest level in mid-adulthood and peaking among older adults and children under 5 years of age, reflecting age-specific vulnerability to renal and cardiovascular injury. The sharp increase in burden in older adults likely results from the convergence of age-related physiological decline and accumulated comorbidities [38]. The accumulation of comorbidities such as hypertension, diabetes, and atherosclerosis, which are common drivers of both CKD and HF, may explain the steep increase in CKD-HF incidence and disability beyond the age of 60 years [17, 39, 40]. Age-related structural and functional cardiac decline, reduced renal reserve, and heightened oxidative stress further exacerbate the interaction between kidney and heart dysfunction [41–43]. In contrast, the unexpectedly high burden among children under 5 years of age may be driven by congenital or hereditary nephropathies, early onset structural heart disease, and poor access to early diagnosis or continuous care in resource-limited settings [44, 45]. Early exposure to acute kidney injury, infection-related nephritis, and malnutrition in childhood are also contributing factors, particularly in low- and middle-income countries [46]. Despite relatively low absolute numbers compared with those of older adults, the high disability burden in children underscores a significant lifelong disability burden and an unmet need for pediatric nephrocardiology integration [47]. Moreover, the steep increase in the ASPR and ASYR after age 75 years aligns with global trends in multimorbidity and frailty [48], underscoring CKD-HF as a geriatric syndrome for which integrated, multidisciplinary care is required. These age-specific disparities highlight the need for targeted strategies: early detection and intervention in children and comprehensive cardiorenal management in older adults.

Etiological Heterogeneity and Evolving Contributors

This study revealed pronounced heterogeneity in the etiology of CKD-HF across age groups and SDI regions. The high proportion of CKD-HF due to other or unspecified causes in children, particularly in low-SDI regions, can be attributed to diagnostic limitations, socioeconomic barriers, and underrecognition of congenital, genetic, and infectious causes of CKD [49, 50]. These findings underscore the urgent need for increased healthcare access, early screening, and improved diagnostic capabilities in these regions. Hypertensive nephropathy and diabetic nephropathy, whose prevalence is steadily increasing, especially in developed regions, are particularly important contributors to CKD-HF among older adults. The increasing incidence of diabetes and hypertension, driven by factors such as lifestyle changes, dietary habits, social stress, and population aging, has significantly contributed to the growing burden of CKD-HF [51, 52]. These trends highlight the urgent need for comprehensive public health strategies, including promoting healthy behaviors, modifying dietary habits, encouraging physical activity, managing stress, and increasing healthcare access for early diagnosis and regular treatment. Emerging cardiorenal-protective therapies, particularly sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, are poised to reshape future treatment paradigms and disease trajectories owing to their demonstrated efficacy in reducing HF hospitalizations and attenuating renal function decline, especially among patients with underlying metabolic factors such as diabetes and hypertension, as substantiated by large-scale randomized trials [53, 54]. Integrating these evidence-based therapies into clinical guidelines and ensuring their equitable implementation are essential public health priorities to mitigate the growing burden of CKD-HF. Chronic glomerulonephritis remains the second most common cause of CKD-HF in individuals under 45 years of age, reflecting the typical onset age of immune-mediated glomerular diseases such as IgA nephropathy and lupus nephritis [55, 56]. Delayed diagnosis and chronic inflammation often lead to irreversible kidney damage and cardiovascular complications, especially in resource-limited settings. These findings emphasize the urgent need for early detection and increased nephrology access to mitigate the long-term cardiorenal impacts in younger populations.

Sociodemographic Disparities and Regional Inequities

The variation in CKD-HF burden across SDI levels and regions primarily reflects health inequities in healthcare resources, a conclusion further corroborated by health inequality analysis. This paradox likely reflects a baseline high disease burden and entrenched structural inequities, such as poor primary care, fragmented nephrology services, and inadequate control of hypertension and diabetes. Despite the slower relative growth in low-SDI regions, these areas consistently maintained the highest ASPR and ASYR of CKD-HF. Furthermore, regions such as Western Sub-Saharan Africa and parts of Latin America reported exceptionally high CKD-HF rates, which are correlated with broader patterns of health system underfunding, high infectious disease burdens, and delayed chronic disease care. In contrast, high-SDI countries presented the most rapid relative increases, possibly driven by population aging, lifestyle transitions, and increased CKD survival duration, leading to a higher prevalence of advanced stages where HF risk escalates. Countries such as the USA and Germany demonstrated rapid escalation in the ASPR and ASYR, indicating an urgent need to strengthen chronic care models and preventive cardiology-nephrology integration. Middle-SDI regions exhibited a large burden of CKD-HF cases with a marked increase, which contrasts with the unequal distribution of healthcare resources, highlighting the urgent need for improved early screening, health education, and optimized resource allocation in these areas.

Health Inequalities and Social Determinants

The global burden of CKD-HF is significantly influenced by disparities in healthcare access, particularly in low-SDI regions. In these areas, fragile healthcare systems, a shortage of trained nephrology professionals, and inadequate diagnostic infrastructure lead to delayed diagnoses and suboptimal treatment [12, 57, 58]. Furthermore, social determinants such as poverty, malnutrition, low health literacy, and a higher prevalence of infectious diseases exacerbate the disease burden. These factors complicate the early detection and management of CKD-HF, contributing to the increased incidence and progression of this disease. In addition, barriers such as geographic inaccessibility, high out-of-pocket costs, and a lack of health insurance prevent timely access to care, further delaying diagnoses and complicating treatment [59–61]. To address these disparities, a multifaceted strategy to improve healthcare infrastructure will is needed; this strategy should include expanding primary care services, increasing early screening for kidney disease, and incorporating mobile health technologies to bridge access gaps in remote areas [62, 63]. Coordinated efforts from governments, healthcare policymakers, international organizations, and local communities are essential to address the root causes of these health inequities [64]. Only through these concerted actions can we hope to reduce the burden of CKD-HF, promote early diagnosis and management, and ultimately improve long-term health outcomes in affected populations globally.

Limitations and Future Directions

Despite offering a comprehensive analysis of the global burden, etiological structure, health inequality, and future projections of CKD-HF, this study has several limitations. First, the accuracy of the estimates is dependent on the quality and completeness of the input data, which are variable across countries – particularly in low-SDI regions and conflict zones where underreporting and limited diagnostic capacity may result in substantial uncertainty. Second, incidence, mortality, or disability-adjusted life years could not be included in this study because of data constraints, limiting the comprehensive assessment of the total disease burden. Furthermore, while the ARIMA-based forecasts are informative, the assumption that past trends will simply continue should be highlighted as a limitation, especially in light of rapid changes in healthcare delivery and population dynamics. Finally, the effectiveness of region-specific public health interventions was not evaluated in this study, which constrains the direct policy applicability of the study findings. In future research, longitudinal clinical data should be incorporated, intervention outcomes should be assessed, and surveillance systems should be strengthened to increase the precision and applicability of CKD-HF burden estimates.

Conclusion

This study provides a thorough analysis of the global, regional, and national CKD-HF burdens from 1990 to 2021, highlighting the ongoing increase in disease burden, shifts in the distribution of underlying causes, and significant health disparities. Improving the accessibility and affordability of cardiorenal care in underdeveloped regions, promoting the integration of cardiology and nephrology in developed regions, implementing region-specific preventive management, promoting early diagnosis, and standardizing treatment should be prioritized in future efforts to ultimately improve long-term health outcomes for globally affected populations.

Acknowledgments

We first appreciate the great work by the Global Burden of Disease Study 2021 collaborators.

Statement of Ethics

This study protocol was reviewed and approved by Ethics Committee of the Fifth Affiliated Hospital (Zhuhai) of Zunyi Medical University, Approval No. [2025KY0068].

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This work was supported by grants from the Science and Technology Program for Social Development of Zhuhai (2420004000107) to Lili Tang, the Guizhou Provincial Health Commission Science and Technology Fund Project (2025GZWJKJXM0453) to Lili Tang, the Science and Technology Key Program for Social Development of Zhuhai (2420004000300) to Xiaoyue Li, and the National Science Foundation of China (82460375) to Xiaoyue Li.

Author Contributions

Lili Tang and Heng Li had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis and contributed equally. Concept and design: Lili Tang, Heng Li, and Xiaoyue Li. Acquisition, analysis, or interpretation of data: Yuhao Wang, Lingting Zhang, and Ziyou Tian. Statistical analysis: Lili Tang, Qiang wu, and Lingting Zhang. Drafting of the manuscript and critical revision of the manuscript for important intellectual content: all authors. Obtaining funding: Lili Tang and Xiaoyue Li. Study supervision: Xiaoyue Li.

Funding Statement

This work was supported by grants from the Science and Technology Program for Social Development of Zhuhai (2420004000107) to Lili Tang, the Guizhou Provincial Health Commission Science and Technology Fund Project (2025GZWJKJXM0453) to Lili Tang, the Science and Technology Key Program for Social Development of Zhuhai (2420004000300) to Xiaoyue Li, and the National Science Foundation of China (82460375) to Xiaoyue Li.

Data Availability Statement

The data used in this study can be obtained online (http://ghdx.healthdata.org/gbd-results-tool). Further inquiries can be directed to the corresponding author.