Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, -1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, -1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI. Bill & Melinda Gates Foundation.

Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. In 2017, cirrhosis caused more than 1·32 million (95% UI 1·27-1·45) deaths (440 000 [416 000-518 000; 33·3%] in females and 883 000 [838 000-967 000; 66·7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2·4% (2·3-2·6) of total deaths globally in 2017 compared with 1·9% (1·8-2·0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21·0 (19·2-22·3) per 100 000 population in 1990 to 16·5 (15·8-18·1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32·2 [25·8-38·6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10·1 [9·8-10·5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3·7 [3·3-4·0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103·3 [64·4-133·4] per 100 000 in 2017). There were 10·6 million (10·3-10·9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33·2% for compensated cirrhosis and 54·8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases more than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH. Bill & Melinda Gates Foundation.

Data about the global, regional, and country-specific variations in the levels and trends of colorectal cancer are required to understand the impact of this disease and the trends in its burden to help policy makers allocate resources. Here we provide a status report on the incidence, mortality, and disability caused by colorectal cancer in 195 countries and territories between 1990 and 2017. Vital registration, sample vital registration, verbal autopsy, and cancer registry data were used to generate incidence, death, and disability-adjusted life-year (DALY) estimates of colorectal cancer at the global, regional, and national levels. We also determined the association between development levels and colorectal cancer age-standardised DALY rates, and calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. All of the estimates are reported as counts and age-standardised rates per 100 000 person-years, with some estimates also presented by sex and 5-year age groups. In 2017, there were 1·8 million (95% UI 1·8-1·9) incident cases of colorectal cancer globally, with an age-standardised incidence rate of 23·2 (22·7-23·7) per 100 000 person-years that increased by 9·5% (4·5-13·5) between 1990 and 2017. Globally, colorectal cancer accounted for 896 000 (876 300-915 700) deaths in 2017, with an age-standardised death rate of 11·5 (11·3-11·8) per 100 000 person-years, which decreased between 1990 and 2017 (-13·5% [-18·4 to -10·0]). Colorectal cancer was also responsible for 19·0 million (18·5-19·5) DALYs globally in 2017, with an age-standardised rate of 235·7 (229·7-242·0) DALYs per 100 000 person-years, which decreased between 1990 and 2017 (-14·5% [-20·4 to -10·3]). Slovakia, the Netherlands, and New Zealand had the highest age-standardised incidence rates in 2017. Greenland, Hungary, and Slovakia had the highest age-standardised death rates in 2017. Numbers of incident cases and deaths were higher among males than females up to the ages of 80-84 years, with the highest rates observed in the oldest age group (≥95 years) for both sexes in 2017. There was a non-linear association between the Socio-demographic Index and the Healthcare Access and Quality Index and age-standardised DALY rates. In 2017, the three largest contributors to DALYs at the global level, for both sexes, were diet low in calcium (20·5% [12·9-28·9]), alcohol use (15·2% [12·1-18·3]), and diet low in milk (14·3% [5·1-24·8]). There is substantial global variation in the burden of colorectal cancer. Although the overall colorectal cancer age-standardised death rate has been decreasing at the global level, the increasing age-standardised incidence rate in most countries poses a major public health challenge across the world. The results of this study could be useful for policy makers to carry out cost-effective interventions and to reduce exposure to modifiable risk factors, particularly in countries with high incidence or increasing burden. Bill & Melinda Gates Foundation.

Background: Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory condition and includes Crohn's disease (CD) and ulcerative colitis (UC). It has been proposed that Vitamin D supplementation may have a beneficial role in IBD. Aim: To characterize the effects of Vitamin D on cathelicidin (hCAP/LL37) gene expression, ESR, and serum hs-CRP levels. Materials and Methods: Ninety UC patients on remission were randomized to receive 300,000 IU intramuscular Vitamin D or 1 mL normal saline as placebo, respectively. Before and 90 days after intervention, serum levels of 25 (OH)-Vitamin D3, PTH, Calcium, ESR, and hs-CRP were measured. Cathelicidin gene expression was also quantified using qRT-PCR. Results: Baseline serum 25-OH-Vitamin D3 levels were not different between the two groups and after intervention, increased only in Vitamin D group (P < 0.001). Hs-CRP levels were lower in Vitamin D group after intervention (Before: 3.43 ± 3.47 vs 3.86 ± 3.55 mg/L, P = 0.56; after: 2.31 ± 2.25 vs 3.90 ± 3.97 mg/L, P= 0.023). ESR decreased significantly in Vitamin D group (Before: 12.4 ± 6.1 vs 12.1 ± 5.3 mm/h, P= 0.77; after: 6.7 ± 4.5 vs 11.4 ± 5.5 mm/h, P< 0.001). The mean fold change in hCAP18 gene expression in Vitamin D group was significantly higher than placebo group. (Mean ± SD: 3.13 ± 2.56 vs 1.09 ± 0.56; median ± interquartile range: 2.17 ± 3.81 vs 0.87 ± 0.53, P<,; 0.001). Conclusion: Decreases in ESR and hs-CRP levels and increase in LL37 gene expression support the hypothesis that Vitamin D supplementation may have a beneficial role in UC patients.

The prevalence of depression in inflammatory bowel disease (IBD) is significantly more than in controls. Some studies assessed the link between vitamin D and depression. The aim of this study was to assess the effect of vitamin D on Beck Depression Inventory (BDI) score in ulcerative colitis (UC) patients. In this double-blind randomized controlled trial, 90 mild to moderate UC patients were assigned to receive a single injection of 300,000 IU vitamin D3 or 1 ml normal saline as placebo. At baseline and 3 months later, measurements of BDI score and serum 25-OH-vitamin D3 were done. Data were compared by independent sample t test, Mann–Whitney U test, and analysis of covariance (ANCOVA). Baseline BDI scores were not statistically different between the two groups (p = .4); scores decreased in the vitamin D group after the intervention (p = .023). Further subgroup analysis regarding baseline serum vitamin D levels and adjusted for baseline BDIs revealed lowering effect of vitamin D on BDI scores only in subgroup with baseline serum vitamin D levels equal to or higher than 30 ng/ml (p < .001). In this study, there was a statistically significant reduction in BDI score in mild to moderate UC patients 3 months after 300,000 IU vitamin D3 injection. Subgroup analysis showed that patients with sufficient baseline vitamin D may benefit from supplementation more than vitamin D–deficient patients, which indicates that higher serum vitamin D levels may be needed for its antidepressant effect.