As the 12th most frequent cancer globally, kidney cancer is a common urological malignancy that accounts for 2.2% of all cancer incidence and 1.8% of all cancer mortality (1). The World Health Organization (WHO) International Agency for Research on Cancer’s most recent statistics from 2020 shows that there are approximately 431,000 new instances of kidney cancer reported globally, and that number is rising annually. Its incidence and death exhibit intricate and varied worldwide epidemiological patterns, with notable regional, age-, and gender-specific variations. Kidney cancer’s disease burden is a serious worry.

Excess body fat is a hallmark of obesity, which is brought on by intricate interplay between behavioral, environmental, genetic, and socioeconomic factors (2). The body mass index (BMI) is a useful metric for determining total body fat. Adults with a BMI of 25-29.9 kg/m² were considered overweight, while those with a BMI over 30 kg/m² were considered obese. From 1990 to 2022, the global age-standardized prevalence of obesity rose markedly—from 8.8% to 18.5% in adult women, 4.8% to 14.0% in adult men (3). Mechanistically, obesity promotes cancer development through chronic inflammation, insulin resistance, dysregulated adipokine secretion, and gut microbiota dysbiosis (4), and a weight loss of more than 5 kg has been shown to reduce overall cancer risk (5). Studies (6–8) have shown that obesity is a major risk factor for renal cancer and have proposed the concept of the obesity paradox. Given the continuing rise in global obesity rates, understanding the impact of obesity on the burden of renal cancer is critical.

Although there are many research on the clinical management of kidney cancer, the disease’s worldwide disease burden has received relatively less attention, and there is a dearth of longitudinal analysis of changes in the burden of kidney cancer. Furthermore, despite the fact that prior research has assessed the influence of particular risk factors, such as occupational exposure to trichloroethylene (9), on the burden of kidney cancer, there is still a dearth of thorough, systematic studies on the burden resulting from high BMI globally, particularly lacking the analysis of disease burden and sociodemographic index (SDI), cohort study and future prediction. This implies that more accurate techniques are required to measure and examine variations in disease load and health outcomes across time periods and demographic groupings in future.

The purpose of this study is to investigate in detail the global burden of kidney cancer as determined by the Global Burden of Disease (GBD 2021) study, as well as trends in high BMI in various categories from 1990 to 2021, including age, gender, SDI quintiles, GBD subcontinent regions, and countries. Using an age-cycle cohort model, we also conducted a combined point regression to examine the disease’s temporal patterns over the previous 30 years. Finally, we project the disease burden to 2040. These results offer important information for the creation of policies and initiatives targeted at reducing obesity worldwide, preventing kidney cancer, and safeguarding high-risk populations.

The significant influence of obesity as a modifiable risk factor is highlighted by the rising incidence of kidney cancer worldwide. The findings of our study indicate that, in tandem with the rise in the prevalence of obesity worldwide (17), the number of deaths has climbed 2.67 times and the disability mortality rate has increased 66.1% between 1990 and 2021. While the ASR of kidney cancer will decline after 2016, the number of kidney cancer cases worldwide will continue to rise between 1990 and 2021. The burden of kidney cancer disease varies significantly by gender, with male bearing a greater burden than female and it is primarily found in areas with low SDI. These negative patterns could provide significant challenges to kidney cancer prevention and treatment.

The trends of various ages and genders demonstrate that the burden of kidney cancer rises with age, peaks in middle-aged and older populations, and varies significantly by gender. Over time, the middle-aged and older adult population has the highest mortality and disability rates from kidney cancer, with 60% of male deaths happening in those between the ages of 60 and 79. This is in line with middle-aged and older people’s cumulative exposure to metabolic diseases linked to obesity and age-related renal impairment. The burden of kidney cancer rises with age, according to the time trend, but the decrease in death and disability loss in the years following 2016 points to the possible advantages of better treatment approaches, such as immune checkpoint inhibitors and tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor (VEGFR) (18), which have been shown to be effective in treating metastatic renal cell carcinoma. There is a clear gender imbalance in disease burden in most age groups. The gender disparity in obesity is a significant factor (19), albeit the possible causes are still unclear. More may also be explained by variations in genetic traits between genders. According to certain research (20, 21), gender has a separate role in kidney cancer survival and progression (22) (such as the protective effect of estrogen on renal cell carcinoma), and effects of social behavior (23) (such as low adherence to the obesity intervention and smoking in men). Therefore, when developing treatment plans for kidney cancer at the patient level and putting population-based preventative initiatives into practice, gender differences should be taken into account.

Regional variations were seen in the worldwide burden of kidney cancer linked to high BMI in 2021, and the annual growth rate of the disease was lower in high-burden regions. South America, North America, Europe, and North Asia are the regions with the highest disease burden, whereas sub-Saharan Africa, South Asia, East Asia, and Southeast Asia are the regions with the lowest disease burden. The treatment of obesity and the availability of healthcare resources and services may have an impact on disease burden. Increased imaging techniques have been linked to an increase in the incidence of kidney cancer in North American and European populations, which has been shown to contribute up to 50% to the inadvertent discovery of tiny renal tumors (24, 25). These areas do, however, also have a rather comprehensive health care system that may offer top-notch medical care, cutting-edge treatment plans, and aid in lowering death and raising survival rates. However, the efficient care and control of kidney cancer is limited in LMICs and areas due to their relatively limited resources in this field. The burden of kidney cancer rises with time due to a combination of factors such as population growth, particularly the aging of the population (26), and the rising incidence of chronic renal disease (27).

The link between the SDI and the disease burden of kidney cancer based on a high BMI is complex and non-linear. Because of their excessive calorie intake and sedentary lifestyle, people with moderate to high SDI are more likely to be obese (28–30). High-calorie foods are consumed more often since they are easy to prepare and affordable, which is in line with the rising obesity rates. On the other hand, because they make up a smaller percentage of the diet, people tend to eat fewer high-fiber items, such as fruits and whole grains, which raises their calorie intake and causes weight gain. This region lies between low and high levels of SDI and faces more unique challenges related to healthcare infrastructure and disease patterns, such as the transition from infectious to chronic diseases (31). The burden in high SDI areas is gradually being lessened thanks to significant advancements in rehabilitation programs and public health policy (32). The World Health Organization Committee on the Elimination of Childhood Obesity (33), which was established in 2014, made a number of recommendations in response to the growing trend of childhood obesity and overweight. WHO member states in Europe have responded by lowering obesity rates in line with this. The disease burden in regions with poor SDI is getting worse and increasing annually as a result of insufficient preventive efforts and delayed diagnostics in transitioning economies. Study’s (1) that used a Bayesian age cohort model predict that by 2030, kidney cancer incidence will increase in the majority of rising nations. These predictions for the upcoming ten years emphasize how urgently worldwide initiatives to combat obesity are needed, especially in areas that are quickly urbanizing. China has a huge population base, and even a smaller change in proportion can have a significant impact on health equality issues. From 1990 to 2021, the proportion of mortality and DALYs in China increased significantly, which emphasizes the dual challenges of addressing population growth and regional development.

Based on high BMI data, joint point regression analysis revealed that the burden of kidney cancer disease increased over time before declining after 2016. According to a 2019 study published by The Lancet Commission (35): obesity rates are rising globally; several evidence-based policy suggestions have not yet resulted in significant changes; Slow progress is caused by policy inertia, and obesity is frequently viewed as a singular problem. As a result, since 1990, the prevalence of kidney cancer disease has been steadily rising, with obesity serving as a risk factor. Age Sex Time Trends in Disease Burden and earlier related studies are in line with the declining trend in disease burden since 2016 (34), underscoring the possible advantages of better treatment approaches (18). Preclinical prevention and BMI reduction should receive more focus when kidney cancer clinical treatment is improved.

By exposing disparate impacts of aging, temporal patterns, and risk specific to a given birth cohort, the age-period-cohort analysis offers crucial insights into the temporal dynamics of high BMI-associated kidney cancer burden. The mortality and handicap loss from kidney cancer linked to high BMI increased dramatically after the age of 40 and peaked between the ages of 60 and 80. The increasing incidence of kidney cancer is consistent with population aging. The period impact emphasizes how the burden of kidney cancer increased gradually between 1990 and 2016 before somewhat declining after that year. This turning phase is in line with early identification initiatives in high regions and the worldwide rollout of targeted therapy (18). The fact that low-SdI areas had restricted access to these advancements, resulting in a persistent rising trend (34), emphasizes how healthcare disparities mediate risk for particular time periods. According to the cohort effect, the risk ratio (RR = 1.5) was considerably higher for those born in 2000 than for those born earlier (RR<1.0). This conclusion is consistent with shifting trends in eating habits and lifestyle choices brought about by economic globalization. The prevalence of ultra-processed diets and sedentary lifestyles, particularly in quickly urbanizing areas, is the cause of the elevated risk in younger generations. Together with decreased physical activity brought on by technology, these dietary changes increase obesity rates, which in turn increase the younger generation’s cumulative exposure to high Bmi-associated carcinogenic pathways. Crucially, there were noticeable variations in the interactions between the cohort and the SDI class. While the low-sdi cohort faced the complex risk of an unregulated food environment and delayed diagnosis, the high-sdi cohort born after 2000 demonstrated slower risk accumulation as a result of progressive public health policies [e.g., Mexican sugar tax (36), Scandinavian school nutrition programs (37)]. These results imply that different exposures to obesogenic environments caused by economic globalization worsen health disparities.

Frontier analysis reveals a rising trend in the burden of high BMI-associated kidney cancer, particularly from 2000-2010. Projections suggest future trends through 2040. Global kidney cancer burden fell from 2016-2030, then surged, suggesting short-term relief measures might be insufficient long-term. First, the projected resurgence may be attributed to demographic aging—particularly in regions with lower socioeconomic development—as well as the phenomenon often termed the “obesity paradox”. This paradox refers to observations that individuals with overweight or obesity sometimes exhibit better survival outcomes compared to those with normal BMI in certain disease contexts, including kidney cancer. For example, a large-scale study involving 50,717 patients (38) reported higher survival among heavier individuals, suggesting that elevated BMI might be linked to certain protective metabolic or nutritional reserves in the short term. Nevertheless, this apparent survival advantage may mask more complex underlying pathophysiological processes, and does not negate the established role of obesity in increasing cancer incidence. Over the longer term, the cumulative effects of population aging and sustained rises in obesity prevalence (39) may overwhelm any initial protective associations, ultimately reversing these patterns and contributing to growing disease burden. Second, healthcare access disparities may contribute significantly. High SDI regions maintain progress through advanced treatments, while low-to-middle SDI areas—with rising obesity and weaker medical systems—face delayed or inadequate interventions. This imbalance could postpone global recovery until post-2030, as early gains in affluent regions are countered by escalating burdens elsewhere. The initial decline likely stems from better early detection, surgical and systemic therapy advances (e.g., targeted and immunotherapy), and public health measures like diet and exercise promotion. To assess the potential bias from incidental diagnoses, a sensitivity analysis excluding regions with the highest rates of incidental detection (e.g., North America and Europe) could be conducted in future studies. Moreover, despite interventions, high BMI may still drive kidney cancer rates, as childhood overweight/obesity is projected to reach 30% globally by 2030 (boys: 34.2%, girls: 27.4%) (40), underscoring the continued challenge of obesity reduction, especially among males. Gender-specific data reveals men will face a disproportionately higher global burden, with rising male incidence rates post-2030 underscoring the need for targeted interventions. These findings emphasize the necessity of dual strategies to mitigate kidney cancer resurgence. To effectively address the rising burden of kidney cancer, a two-pronged approach is essential. First, we must strengthen preventive measures—implementing tighter food regulations, prioritizing obesity screening for men, and expanding community-based weight management programs. Targeted interventions could mitigate the projected rise in kidney cancer burden, particularly in middle- and low-SDI regions. Second, we need to guarantee fair and widespread access to diagnostic tools and treatments worldwide. Without these fundamental reforms, any short-term reduction in kidney cancer cases will likely prove fleeting rather than sustainable. Our projections are based on current epidemiological trends and do not account for potential disruptions such as global pandemics, major policy shifts, or breakthroughs in obesity or cancer therapeutics. Future studies should incorporate scenario-based modeling to better capture these uncertainties.

Our study systematically evaluated the global trend of high BMI-associated kidney cancer from 1990 to 2021, analyzed the spatial distribution characteristics, temporal trends and age-gender differences in 204 countries and regions. Finally, it makes a prediction for the future to 2040. Full-dimensional data coverage and multi-method integration enhance the conclusions’ resilience and offer accurate epidemiological support for regionally tailored preventive and control. There are various restrictions on this study. First, in areas where data is scarce, such as parts of sub-Saharan Africa and South Asia, cancer registrations are incomplete or non-existent, which poses big problems. In these places, data on kidney cancer caused by high BMI are not directly measured, but are derived from models-using information from other areas with sufficient data, so the results may be inaccurate. These models are based on assumptions such as the relationship between BMI and cancer risk and medical conditions that are the same globally, but these assumptions may not hold true locally. And because many cases are not diagnosed, the model is likely to underestimate the real burden. The same assumption affects global data: even a small amount of systematic error in low-SDI regions with large populations can distort global totals and trends. For example, if a “detection gap” arises-obesity rates have increased but diagnoses have not kept up-it may mislead people into thinking that the disease burden is increasing, or even lead to low future global estimates. Second, diagnostic misclassification (e.g., incidental testing and symptom testing) may influence temporal trends, especially in high-income areas. Third, although GBD was adjusted for high BMI attribution, residual confounding from unmeasured variables (e.g. genetic susceptibility or environmental exposure) cannot be excluded. And we adjusted for several confounders in the GBD model, factors such as smoking, hypertension, and occupational exposures (e.g., trichloroethylene) may interact with high BMI in influencing kidney cancer risk. Future studies should explore these interactions in more depth. Additionally, variations in health systems, diagnostic capabilities, and case definitions across countries may affect the accuracy and comparability of DALY estimates, particularly in cross-national comparisons. Finally, the Age-Period-Cohort model assumes a linear relationship of cohort effects, which may oversimplify the complex interplay between obesity and renal carcinogenesis. However, the GBD study provides us with global data and provides an unprecedented opportunity to investigate the global burden. Here are some suggestions based on our study. Individuals with high BMI should pay attention to consuming high fiber foods such as fruits and whole grains, combined with tobacco control measures to reduce the synergistic carcinogenic effect with BMI, particularly in men aged 55–79 years. Each country should impose restrictions on high-calorie advertising and promote community health campaigns within factories. Low and middle SDI areas should improve the diagnostic and treatment techniques, strengthen the early kidney cancer screening and awareness of chronic disease management, especially for the middle-aged and older adult population.

In summary, this study highlights the significant and growing burden of high BMI-associated kidney cancer, particularly among men aged 55–79 years. Although treatment advances led to a temporary decline after 2016, a rebound is projected after 2030 due to rising obesity rates, population aging, and persistent healthcare disparities. To alleviate this problem, we recommend gender-specific measures, such as targeted screening for men aged 55–79 in high-SDI areas, community weight loss programs in developing economies, and policies to ensure that everyone has equitable access to advanced diagnosis and treatment. Urgent global action is needed to address the dual challenges of obesity and kidney cancer control.