Background Chronic kidney disease (CKD) is common and ranks among the leading causes of mortality and morbidity. This analysis aimed to present global CKD estimates using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to inform evidence-based policies for CKD identification and treatment. Methods This analysis focused on adults aged 20 years and older over the period 1990 to 2023, from 204 countries and territories. Data sources used were published literature, vital registration systems, kidney failure treatment registries, and household surveys. Estimates of CKD burden, including deaths, incidence, prevalence, and disability-adjusted life-years (DALYs), were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool. A comparative risk assessment approach estimated the proportion of cardiovascular deaths attributable to impaired kidney function and estimated risk factors for CKD. Findings Globally, in 2023, 788 million (95% uncertainty interval 743–843) people aged 20 years and older were estimated to have CKD, up from 378 million (354–407) in 1990. The global age-standardised prevalence of CKD in adults was 14·2% (13·4–15·2), a relative rise of 3·5% (2·7–4·1) from 1990. The region with the highest age-standardised prevalence was north Africa and the Middle East (18·0%; 16·9–19·4). Most people had stage 1–3 CKD, with a combined prevalence of 13·9% (13·1–15·0). In 2023, CKD was the ninth leading cause of death globally, accounting for 1·48 million (1·30–1·65) deaths, and the 12th leading cause of DALYs, with an age-standardised DALY rate of 769·2 (691·8–857·4) per 100 000. Impaired kidney function as a risk factor accounted for 11·5% (8·4–14·5) of cardiovascular deaths. High fasting plasma glucose, body-mass index, and systolic blood pressure were all leading risk factors for CKD DALYs. Interpretation CKD is a major global health issue, with rising prevalence and increasing importance as a cause of death and as a risk factor for cardiovascular death. A better understating of aetiology, appropriate screening, and implementation programmes are needed to translate advances in CKD treatment into improved patient outcomes. Funding Gates Foundation, Wellcome, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates health loss from migraine, tension-type headache, and medication-overuse headache. This study presents updated results on headache-attributed burden from 1990 to 2023, along with clinical and public health implications. Methods: Data on the prevalence, incidence, or remission of migraine, tension-type headache, and medication-overuse headache were extracted from published population-based studies. We used hierarchical Bayesian meta-regression modelling to estimate global, regional, and country-level prevalence of headache disorders. For the first time in GBD 2023, age-specific and sex-specific estimates of time in symptomatic state were applied by meta-analysing individual participant data from 41 653 individuals from the general populations of 18 countries from all parts of the world. Disability weights were applied to calculate years lived with disability (YLDs). Since medication-overuse headache is a sequela of a mistreated primary headache (due to medication overuse), its burden was reattributed to migraine or tension-type headache, informed by a meta-analysis of three longitudinal studies. Findings: In 2023, 2·9 billion individuals (95% uncertainty interval 2·6–3·1) were affected by headache disorders, with a global age-standardised prevalence of 34·6% (31·6–37·5) and a YLD rate of 541·9 (373·4–739·9) per 100 000 population, with 487·5 (323·0–678·8) per 100 000 population attributed to migraine. The prevalence rates of these headache disorders have remained stable over the past three decades. YLD rates due to headache disorders were more than twice as high in females (739·9 [511·2–1011·5] per 100 000) as in males (346·1 [240·4–481·8] per 100 000). Medication-overuse headache contributed 58·9% of the YLD estimates for tension-type headache in males and 56·1% in females, as well as 22·6% of the YLD estimates for migraines in males and 14·1% in females. Interpretation: Headache disorders, in particular migraine, continue to be a major global health challenge, emphasising the need for effective management and prevention strategies. Much headache-attributed burden could be averted or eliminated by avoiding overuse of medication (including over-the-counter medication), underscoring the importance of public education. Funding: Gates Foundation.

Background Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. Methods Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. Findings In 2023, there were an estimated 2·30 million (95% uncertainty interval [UI] 2·01 to 2·61) breast cancer incident cases, 764 000 deaths (672 000 to 854 000), and 24·1 million (21·3 to 27·5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44·2 per 100 000 person-years [31·2 to 58·4]), the age-standardised mortality rate (ASMR) was the highest (24·1 per 100 000 [16·8 to 31·9]). The highest ASIR was in the high-income group (75·7 per 100 000 [67·1 to 84·0]), and the lowest ASMR was in the upper-middle-income group (11·2 per 100 000 [10·2 to 12·3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147·2% (38·1 to 271·7), compared with a 1·2% (–11·5 to 17·2) change in the high-income group. The ASMR decreased in the high-income group, changing by –29·9% (–33·6 to –25·9), but increased by 99·3% (12·5 to 202·9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28·3% (16·6 to 38·9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3·56 million (2·29 to 4·83), with 1·37 million (0·841 to 2·02) deaths. Interpretation The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2·5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. Funding Gates Foundation, St Jude Children's Research Hospital.

Background: The global burden of sepsis, a life-threatening dysregulated host response to infection leading to organ dysfunction, remains challenging to quantify. We aimed to comprehensively estimate the global, regional, and national burden of sepsis, including the impact of the COVID-19 pandemic and underlying causes of sepsis-related deaths with co-occurring infectious syndromes. Methods: We used multiple cause-of-death, hospital, minimally invasive tissue sampling, and linked death certificate and hospital record data representing 149 million deaths, covering 4290 location-years with mortality estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to capture explicit and implicit sepsis cases and deaths. We estimated age-location-sex-specific fractions of sepsis-related deaths from 195 underlying causes of death and 22 infectious syndromes from 1990 to 2021 using binomial logistic regression models, and estimated sepsis-related deaths using GBD cause-specific mortality estimates. Using 250 million hospital admissions and 7·82 million deaths from hospital data, representing 1310 location-years, we modelled case fatality rates by use of binomial logistic regression, applied to sepsis death estimates to estimate sepsis incidence by age, location, and year. Findings: In 2021, we estimated 166 million (95% uncertainty interval 135–201) sepsis cases and 21·4 million (20·3–22·5) all-cause sepsis-related deaths globally, representing 31·5% of total global deaths. Sepsis-related deaths decreased between 1990 and 2019, followed by a surge in 2020 and 2021. As of 2021, individuals aged 15 years and older experienced increases across incidence (230%) and mortality (26·3%) since 1990. Those aged 70 years and older had the highest sepsis-related mortality in 2021 (9·28 million [8·74–9·86] deaths). Sepsis-related deaths from infectious underlying causes decreased from 11·8 million (11·1–12·5) in 1990 to 8·34 million (7·72–9·01) in 2019, then increased by 86·4% to 15·5 million (14·7–16·4) in 2021. Sepsis-related mortality due to non-infectious underlying causes of death increased from 4·69 million (4·35–5·05) in 1990 to 5·81 million (5·40–6·25) in 2021; the leading non-infectious underlying causes of death with sepsis were stroke, chronic obstructive pulmonary disease, and cirrhosis. In 2021, bloodstream infections inclusive of HIV and malaria (3·08 million [2·83–3·35]) and lower respiratory infections inclusive of COVID-19 (11·33 million [1·20–1·47]) were the most prominent infectious syndromes complicating sepsis-related deaths from non-infectious underlying causes, representing a consistent trend since 1990. Interpretation: The global burden of sepsis increased in 2020 and 2021, reversing progress from 1990. Sepsis incidence and mortality increased in people aged 15 years and older, especially those aged 70 years and older, and as a complication of non-infectious underlying causes of death such as stroke, primarily through bloodstream infections and lower respiratory infections. The global burden of sepsis is substantial, and sepsis is increasingly a complication of non-infectious causes of death. Funding: Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

Background Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses. Methods GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0–19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs). Findings Globally, in 2023, there were an estimated 377 000 incident childhood cancer cases (95% UI 288 000–489 000), 144 000 deaths (131 000–162 000), and 11·7 million (10·7–13·2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27·0% (15·5–36·1) globally, from 197 000 (173 000–218 000) in 1990, but increased in the WHO African region by 55·6% (25·5–92·4), from 31 500 (24 900–38 500) to 49 000 (42 600–58 200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26·5% (26·5–26·5) in GBD 2017 to 10·5% (8·1–13·1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47·3% (42·2–52·0) of global childhood cancer deaths in 2023. Interpretation Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum. Funding St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.