Globally, chronic kidney disease (CKD) has emerged as one of the leading causes of mortality and disease burden; approximately 843.6 million patients were affected by CKD worldwide in 2017 [1]. Despite predominately manifesting in older populations, it is estimated that adolescents and young adults (AYAs) with CKD are vulnerable groups with poor treatment outcomes [2]. In addition, the increasing rates of childhood obesity, lipid abnormalities, diabetes mellitus (DM), and hypertension indicate that the number of young adults with CKD is likely to increase [3,4].

Accumulated evidence has reported that early-onset CKD (e.g., diagnosis before the age of 40 years) experienced many complex challenges with lower quality of life, increased healthcare utilization, and limited employment, independence, and relationships compared with healthy counterparts [5,6]. In addition, physiological complications of CKD, such as hypertension, dyslipidemia, hyperphosphatemia, and chronic inflammation, underlie many long-term outcomes and are likely to accumulate with disease duration [7,8]. For example, cardiovascular mortality is excessive in young adults with end-stage renal disease, with an increase 700-fold in 25- to 34-year-old patients undergoing dialysis [9]. Therefore, understanding the global burden of CKD in AYAs and its attributable risk factors is paramount.

Previous studies have reported on the global burden of CKD and its attributable risk factors in all age groups from 1990 to 2017 [10] and sex differences in CKD-associated mortality from 1990 to 2019 [11], or the burden from Asia [12,13], North Africa and Middle East region [14], and the United States [15]. AYAs represent a transitional phase between childhood and adulthood, characterized by numerous physical, psychological, and social changes [16]. However, existing health services often overlook their age-specific treatment and care needs, unlike services for children and older adults [17]. According to the age grouping and estimation methods of the Global Burden of Diseases (GBD) 2019, the age range of 15–39 years is widely recognized as the AYAs [17,18]. To date, no study has specifically described the global burden of CKD and its attributable risk factors in AYAs. Therefore, in the present study, we estimated the global epidemiological characteristics and secular trends of CKD, as well as the attributable risks for CKD in AYAs (15–39 years).

Based on data from the GBD 2019, we report an increase in ASIR in AYAs between 1990 and 2019, with the highest incidence concentrated in countries with a middle SDI and among females. Conversely, downward trends were found for the ASMR and ASMR, with the highest burden in countries with a low SDI. In addition, the secular trends in age-standardized incidence, death, and DALY rates, as well as patterns of attributable risk factors for early-onset CKD were heterogeneous across regions and countries. These findings indicated that preventing and controlling CKD in AYAs is still one of the great challenges.

According to the GBD study, AYAs aged 15 to 39 years constitute a substantial portion of the global population and represent a heterogeneous population [17,18]. Accumulating evidence has reported the burden of cardiovascular disease , type 2 DM, and cancer [17,18,24]. However, no studies have specifically reported the global burden of CKD in AYAs. In contrast to the stable trends in global age-standardized prevalence and mortality rates of CKD in all age groups [10,11], we found that AYAs tended to show an increasing incidence of CKD globally. Additionally, compared to children and the elderly, the incidence rate of CKD among AYAs has shown a more pronounced increasing trend over the past three decades [25]. More importantly, the PAF of CKD risk factors differed between different populations. For example, high fasting plasma glucose was the most important risk factor for CKD burden in the overall global population [10], whereas high SBP mainly accounted for CKD burden in AYAs. A potential explanation seems to be that AYAs may be more prone to the effects of high SBP [4,24]. Those suggested that targeted strategies are needed for the prevention and management of CKD in AYAs.

Despite all SDI regions showing upward trends, the middle SDI saw the most significant increase in ASIR since 1990. The reasons for the observed changes in CKD incidence are unclear, which may contribute to a combination of factors related to risk factor prevalence, healthcare access, the quality of care, population demographics, data quality, healthcare awareness, and socioeconomic conditions [1,26]. For example, a more universal detection and lower glomerular filtration rate boundary value was used to indicate kidney replacement therapy in middle SDI regions than other regions [27].

The burden of CKD in AYAs appeared to be increasing in the high SDI region, although downward trends were reported in low, middle, and middle-high SDI. Similar results were found in region-specific burden studies [13,14,28]. The potential reasons related to the increasing burden of CKD in high SDI regions may contribute to the high prevalence and inadequate control of risk factors for CKD in these regions, such as DM, hypertension, and high BMI [29]. The improvement of medical technology and effective healthcare reform in low-income countries may also be related to a decline in the CKD burden in these regions [28]. However, the disparities existing in CKD burden between different SDI regions will be further increased if these trends continue. Therefore, more resources for CKD-related prevention and therapeutic services are needed in countries with an increasing burden of early-onset CKD, particularly in locations with high SDI.

Marked variations in CKD burden were observed between the sexes, with a higher incidence of CKD in females and higher mortality in males. This sex disparity can be explained partially by disparities in behavioral and metabolic risk factors, disparities in access to kidney care levels, and differences in the underlying pathophysiology of disease [30,31]. For example, some risk factors for CKD, such as DM and hypertension, were more prevalent in females due to factors like obesity or hormonal changes related to pregnancy [18]. In addition, females may be more likely to seek medical attention and undergo health screenings [32], which could lead to earlier detection of CKD cases. Moreover, higher risk of occupational exposures, lower treatment compliance, faster progression to kidney disease, and lower use of health services among males may explain higher rates of CKD mortality [30]. Taken together, the heterogeneity by sex in CKD burdens calls for more attention to the high incidence of early-onset CKD in females and the high mortality and DALY attributable to CKD in males, and targeted preventative programs should be considered to control sex-specific risk factors and improve survival in young patients.

Globally, high SBP and fasting plasma glucose were the leading risk factors for mortality and DALYs from CKD in AYAs, which is consistent with previous studies of all age groups in low-and middle-income countries [28]. In addition, the high SDI region had the highest ASIRs of CKD due to hypertension [33]. Notably, due to the complexity of CKD etiology, a proportion of CKD deaths and DALYs are not directly attributable to DM or hypertension but can result from various other causes, such as glomerulonephritis and unspecified causes. Therefore, efforts to prevent and manage hypertension and DM [34,35], as well as kidney disease screening and early intervention for glomerulonephritis [36] should be strengthened and supported in AYAs.

To our knowledge, this is the first study to explore the global burden of CKD in AYAs. However, the GBD study had several limitations described and discussed elsewhere [19]. First, several data sources were included when estimating disease mortality and incidence for each country. Geographical proximity and predictive covariates are used to make estimates for countries with sparse or absent data, which might lead to an overestimation of the burden of CKD [10]. Second, most CKD cases were defined relying on one measurement of eGFR and albumin to creatinine ratio in GBD and lack of repeated measures evaluation. Previous studies suggested that CKD cases might be overestimated by using a single measurement of eGFR or albuminuria [37]. In addition, ascertainment of causes of CKD depends on the validity of ICD coding; however, CKD was often caused by comorbid conditions, which might lead to uncertainty about the definite underlying cause of CKD [38]; and thus, a proportion cause of CKD attributed to glomerulonephritis might be overshadowed by the large proportion of “other/unspecified.” Finally, although GBD methodologies and results are considered reliable and robust, they are necessarily limited by the quality of the available data and measurement methods, such as the exchangeability of data quality among individuals and changes in testing practices over time. For example, improvements in healthcare infrastructure and diagnostic capabilities globally might have led to enhanced detection of CKD, thereby influencing the rising incidence of CKD, especially in low SDI regions [28]. Therefore, the results should be interpreted with caution and further studies still be needed.

In conclusion, the present study showed that the number of CKD patients in AYAs has overall increased from 1990 to 2019, although the global ASR of death has generally decreased. Countries in a middle SDI experienced the largest increase in ASIR, while countries in a low SDI experienced the highest rate of age-standardized death. High SBP, high fasting plasma glucose, and high BMI are the main attributable risk factors for the burden of CKD. Furthermore, variations in the CKD burden and its attributable risk factors in different countries and regions highlight the critical role of targeted prevention strategies, including recognition and comprehensive control of established risk factors in AYAs and aggressive treatment of risk factors in high-risk populations, especially in hypertension, DM, and obesity patients aged 15 to 39 years.