Introduction

As the ageing population accelerates and the disease spectrum shifts, older adults are at greater risk of developing chronic kidney disease (CKD), posing a significant health risk and economic burden worldwide [1–6]. CKD is one of the most common chronic diseases worldwide, affecting approximately more than 10% of the global population, and it is projected to become the fifth most important factor affecting life expectancy by 2040 [7,8]. It is a well-established physiological phenomenon that glomerular filtration rate declines with age, typically decreasing at a rate of approximately 0.8 ml/min per year from the age of 40 onwards [9]; consequently, the older adult population is at high risk of chronic kidney disease. Statistics show that the prevalence of chronic kidney disease among the elderly is more than three times that of adolescents, whilst the relative risk of developing kidney damage is as high as 329 times that of the general adult population [6]. Of particular concern is the fact that chronic kidney disease is also associated with a significantly increased risk of dementia, disability and mortality among older adults [10–14]. There is significant heterogeneity in the health status of older adults, and the ageing process exhibits non-linear characteristics. Although the notion that ‘70 is the new 60’ reflects an overall improvement in the health status of younger older adults [15], it also implies that the burden of disease may become more concentrated and pronounced in later life (typically referring to those aged 75 and over). In light of this, authoritative bodies such as the World Health Organization (WHO) have progressively adopted higher age thresholds in their reports to identify sub-groups of older adults requiring particular attention, as this group is more susceptible to disease and faces a significantly increased risk of adverse health outcomes [16–20]. It is worth noting that the health and economic burden of chronic kidney disease on patients, families and society within this group also tends to increase with age.

Although the Global Burden of Disease (GBD) studies have extensively described the epidemiological patterns of chronic kidney disease (CKD), there remains a lack of in-depth analysis regarding the evolution of the disease burden and its driving factors among the very elderly (aged ≥ 75 years) [13,21–24]. Given that renal function declines physiologically with age, and that the very elderly have high rates of comorbidity and significant heterogeneity in treatment response, the epidemiological characteristics, disease progression and health outcomes of CKD in this population may differ fundamentally from those in younger age groups. By conducting a dedicated analysis of the GBD 2021 data for individuals aged 75 years and older, this study aims to reveal the independent impact of extreme ageing on the burden of CKD and to assess differences in the distribution of CKD risk among the very elderly across varying levels of socio-economic development. This will provide an age-specific evidence base for the formulation of targeted strategies to protect renal health in older adults, rather than a simple replication of trends observed in the general population.

Methods

This study was reported in accordance with the STROBE (Standard for Reporting Observational Studies in Epidemiology) guidelines [25] and was approved by the Ethics Committee of the Center for Health Sciences at Peking University. As the study involved a secondary analysis of the publicly available, de-identified GBD database and did not involve any personally identifiable information, the Ethics Committee granted an exemption from informed consent. With advances in public health and increased life expectancy, the traditional age threshold of 65 years is no longer sufficient to distinguish health heterogeneity within the population [26–28]. To focus on the subgroup of older adults with the highest disease burden and most significant health vulnerabilities, this study explicitly defines the study population as older adults aged 75 years and above; this threshold aligns with the definition of ‘older adults’ used by organizations such as the World Health Organization.

Results

CKD in older adults: Global Trends

Global burden and temporal changes.

From 1990 to 2021, a total of 288,520,255 (95% UI: 288,514,827–288,523,786) individuals aged 75 years and older were included in the analysis. The global epidemiology of CKD in this population showed divergent trends across different metrics. While the number of prevalent cases increased by 140.33% to 126,963,771 (95% UI: 116,043,499–137,447,863) in 2021, the age-standardized prevalence rate exhibited a slight decline, from 4,502.1 (95% UI: 4,103.5–4,911.2) to 4,400.4 (95% UI: 4,021.9–4,763.7) per 100,000 population, corresponding to an estimated annual percentage change (EAPC) of −0.06% (95% UI: −0.09% – −0.03%).

In contrast, the age-standardized incidence, mortality, and DALYs rates all demonstrated significant increases. The incidence rate rose from 1.55% to 1.82% (EAPC = 0.50%; 95% UI: 0.47–0.53). The mortality rate increased from 160.55 (95% UI: 145.34–178.01) to 246.90 (95% UI: 213.17–267.13) per 100,000 (EAPC = 1.55%; 95% UI: 1.48–1.61). Similarly, the DALYs rate showed substantial growth (EAPC = 1.07%; 95% UI: 1.02–1.12).

Age and sex patterns.

A critical divergence was observed in age-specific trends. The EAPC for incidence decreased progressively with advancing age, from 0.66% (95% UI: 0.62%–0.70%) in the 75–79 years group to 0.10% (95% UI: 0.02%–0.19%) in the 90–94 years group. Conversely, the EAPC for mortality showed a marked, graded increase with age, from 0.79% (95% UI: 0.75%–0.82%) in the 75–79 years group to 2.29% (95% UI: 2.13%–2.45%) in those aged ≥ 95 years.

Sex disparities were also evident. In 2021, women had higher prevalence and incidence rates across all age groups. However, men bore a higher burden of mortality and DALYs. Notably, the rate of increase in mortality (EAPC) was steeper for women than for men in every age stratum (Fig 1).

Download:

• PNG
  larger image
• TIFF
  original image

Fig 1. Age-Specific differences of CKD in the older adults in 2021, by Gender (A) prevalence (B) incidence (C) mortality (D) DALYs.

https://doi.org/10.1371/journal.pone.0354811.g001

CKD in older adults: SDI regional trends

The burden of CKD among older adults varied markedly across SDI regions, with distinct patterns in static levels and temporal trends. In 2021, the high-SDI region carried the largest absolute burden, accounting for the most prevalent cases (44.2 million), incident cases (2.35 million), deaths (246,298), and DALYs (3.35 million).

Divergent trends in prevalence and mortality.

A key observation was the contrasting relationship between SDI and trends in prevalence versus mortality. The age-standardized prevalence rate showed a slight increase in high-SDI regions (EAPC = 0.07%; 95% UI: 0.03%–0.11%) but significant decreases in high-middle and middle SDI regions (EAPC = −0.21%; 95% UI: −0.27% – −0.14% and EAPC = −0.08%; 95% UI: −0.13% – −0.03%, respectively), while remaining relatively stable in low and low-middle SDI regions.

In stark contrast, the mortality rate presented a more complex picture. Throughout the study period, the low-SDI region consistently had the highest mortality rate (336.51, 95% UI: 300.78–382.43, per 100,000 in 2021). However, the most rapid annual increase in mortality occurred in the high-SDI region (EAPC = 2.56%; 95% UI: 2.42%–2.71%), far exceeding the growth in low-SDI regions (EAPC = 0.41%; 95% UI: 0.30%–0.53%) (Fig 2C). Consequently, the high-SDI region’s mortality ranking rose from fourth highest in 1990 to second highest in 2021.

Download:

• PNG
  larger image
• TIFF
  original image

Fig 2. Age-Specific differences of CKD in the older adults from 1990 to 2021, by SDI number (A) prevalence (B) incidence (C) mortality (D) DALYs.

https://doi.org/10.1371/journal.pone.0354811.g002

Incidence and DALYs: growth and inequality.

Trends in incidence and DALYs further illustrated the heterogeneity. The greatest increase in the incidence rate was observed in the middle-SDI region (EAPC = 1.26%; 95% UI: 1.23%–1.28%), while the increase was most modest in the high-SDI region (EAPC = 0.26%; 95% UI: 0.21%–0.30%) (Fig 2B). The number of incident cases in the low-middle SDI region surged by 313% from 1990 to 2021.

Similarly, the number of CKD-associated DALYs increased dramatically in all regions, with the most substantial relative increase (227%) and the highest final count in the high-SDI region. The low-SDI region had the smallest increase in the DALYs rate (EAPC = 0.22%; 95% UI: 0.14%–0.30%) (Fig 2D).

CKD in older adults: geographic regional and national-level trends

Geographic regional of disease burden.

The burden of CKD among older adults exhibited profound geographic disparities. In 2021, the highest age-standardized rates were concentrated in different regions: Central Asia had the highest prevalence rate, while North Africa and the Middle East had the highest mortality rate, and Central Sub-Saharan Africa had the highest DALYs rate. This pattern aligns with the finding that the heaviest burden often falls on low- and middle-SDI regions.

Temporal trends (1990–2021) also varied markedly. While the age-standardized incidence of CKD increased in all 21 GBD regions, the growth was most rapid in Andean Latin America (EAPC = 2.34%; 95% UI: 2.20%–2.48%) and slowest in High-income North America (EAPC = 0.16%; 95% UI: 0.10%–0.22%). Mortality rates increased universally, with the steepest rise observed in Eastern Europe (EAPC = 4.49%; 95% UI: 3.84%–5.14%) and the most modest in Eastern Sub-Saharan Africa (EAPC = 0.27%; 95% UI: 0.20%–0.35%). In 2021, a majority of regions (13/21) had mortality rates above the global average (Fig 3).

Download:

• PNG
  larger image
• TIFF
  original image

Fig 3. Correlation analysis of CKD in the older adults, by 21 geographic regions (A) prevalence (B) incidence (C) mortality (D) DALYs.

https://doi.org/10.1371/journal.pone.0354811.g003

National-Level burden and inequality.

Analysis across 204 countries and territories revealed even starker inequalities. The People’s Republic of China contributed the largest number of prevalent cases, incident cases, deaths, and DALYs globally in 2021, reflecting its large aging population. Critically, the distribution of the mortality burden was highly skewed. In 2021, the vast majority of countries (169 out of 204, 82.8%) had age-standardized mortality rates above the global average (246.90, 95% UI: 213.17–267.13, per 100,000), underscoring the pervasiveness of elevated CKD-related death risk in the older adult population worldwide (Fig 4).

Download:

• PNG
  larger image
• TIFF
  original image

Fig 4. GBD 2021 data on CKD among older adults in 204 countries (A) prevalence (B) incidence (C) mortality (D) DALYs.

https://doi.org/10.1371/journal.pone.0354811.g004

Discussion

This study provides a comprehensive analysis of the global burden of chronic kidney disease (CKD) from 1990 to 2021, specifically focusing on adults aged 75 years and older. We found that while the age-standardized prevalence rate remained relatively stable, the incidence, mortality, and disability-adjusted life years (DALYs) rates increased significantly. These burdens exhibited substantial heterogeneity across ages, sexes, socio-demographic levels, and geographic regions. Our findings confirm and extend prior knowledge by delineating the unique epidemiological profile of CKD in the fastest-growing segment of the global population—the oldest-old [38,39].

The observed divergence between stable prevalence and rising mortality presents a “high-age CKD paradox” in this population. CKD is a disease with diverse aetiologies influenced by genetic, metabolic, and environmental factors, whose precise mechanisms in older adults require further exploration [38]. The marginal decline in prevalence may reflect advancements in managing hypertension and cardiovascular comorbidities over the past decades. However, the marked rise in incidence could be driven by the increasing prevalence of key risk factors like diabetes and obesity in aging societies, coupled with improved detection. The steep acceleration in mortality, particularly with advancing age, underscores that extreme age itself is a critical amplifier of risk for fatal outcomes. This is likely multifactorial, involving cumulative renal function decline, heightened vulnerability to acute kidney injury, and the blunted physiological response to disease and treatment commonly seen in advanced age [39].

Our analysis reveals a complex relationship between socio-demographic development and CKD burden. Consistent with some studies, we found a negative correlation between DALYs levels and SDI (Spearman r = −0.47; p < 0.001). This may be partly explained by challenges in low-SDI regions, where non-specific symptoms of CKD (e.g., dizziness, weakness) often lead to delayed diagnosis [40–42]. Failure to identify and treat high-risk patients in a timely manner likely increases progression to end-stage renal disease, elevating both premature death and disability, thereby contributing to higher DALYs[40–42].

However, we also observed a “high-SDI region paradox”: although low-SDI regions carried the highest mortality rates throughout the study period, the fastest growth in mortality and DALYs occurred in high-SDI regions. This counterintuitive finding may be primarily related to the more advanced degree of population ageing in high-SDI areas [43]. The proportion and absolute number of the “oldest-old” are greater in these regions, which likely drives a rapid increase in the number of individuals at the highest risk for CKD-related death. Furthermore, the strong positive correlation between SDI and the EAPC of incidence (Spearman r = 0.64; p < 0.0001) may not solely indicate a higher risk of developing CKD. Instead, it could reflect more intensive diagnostic efforts and better case ascertainment in well-resourced health systems, alongside a higher prevalence of lifestyle risk factors such as diabetes and hypertension. Diabetes mellitus, a major driver of CKD [11,44,45], is more prevalent in high-SDI settings, and its coexistence with an aging population may compound the increase in CKD incidence and severe outcomes [46–48].

Conclusions

Based on the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, this study presents a comprehensive, longitudinal assessment (1990–2021) of the global burden of chronic kidney disease (CKD) among adults aged ≥75 years. Our analysis reveals a critical shift in the epidemiological profile of CKD within this rapidly growing demographic: the burden is evolving from a state of high prevalence toward one characterized by elevated incidence, accelerated mortality, and substantial health loss. A notable paradox emerges—a stable or even slightly declining prevalence coexists with sharply rising mortality—highlighting how extreme population aging intensifies disease progression and exacerbates the risk of adverse outcomes, thereby representing a major and growing public health challenge.

The distribution of this burden is markedly heterogeneous and closely tied to levels of socio-demographic development. Low- and middle-income regions continue to carry the heaviest absolute burden of CKD-related deaths and healthy life years lost, largely attributable to systemic gaps in healthcare access, delayed diagnosis, and suboptimal disease management. In these settings, strengthening foundational kidney health systems and advancing universal health coverage remain urgent priorities to reduce preventable morbidity and mortality. In contrast, high SDI regions—despite superior healthcare infrastructure and diagnostic capacity—are experiencing the most rapid increase in CKD-related mortality. This pattern signals an epidemiological transition wherein the principal challenge is shifting from “high mortality due to untreated disease” to “high morbidity and mortality driven by advanced population aging, intensive case finding, and the rising prevalence of lifestyle-related risk factors.”

In summary, the global burden of CKD in older adults is not only increasing in magnitude but also growing in complexity. Effectively addressing this dual challenge necessitates a move away from uniform, one-size-fits-all approaches toward the design and implementation of stratified, context-specific strategies for prevention, screening, management, and long-term care. Such strategies must be carefully tailored to the distinct epidemiological patterns and demographic realities observed across different geographic regions and age strata within the older population. By delineating the evolving landscape of CKD in the oldest-old worldwide, this study provides a robust, evidence-based foundation to inform health policy formulation, guide optimal resource allocation, and steer future research aimed at mitigating the growing burden of CKD in an aging global population.

Supporting information

Acknowledgments

The author sincerely thanks the staff and participants of GBD2021 database for their contributions.