Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF-receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.

Introduction: Hypertension is the leading preventable cause of premature death worldwide. We aimed to examine the global disparities of hypertension prevalence, awareness, treatment, and control in 2010 and compare secular changes in these disparities from 2000 to 2010. Methods: We searched MEDLINE from January 1995 to December 2014 and supplemented with manual searches of references from retrieved articles. A total of 135 population-based studies with 968,419 individuals aged ≥20 years from 90 countries were included. Sex-age-specific prevalences of hypertension from each country were applied to population data to calculate the number of hypertensive adults in each region and globally. Proportions of awareness, treatment, and control from each country were applied to hypertensive populations to obtain regional and global estimates. Results: An estimated 30.2% (95% confidence interval, 30.1-30.4%) of the world’s adult population in 2010 had hypertension; 28.6% (28.3-28.9%) in high-income countries and 30.3% (30.1-30.5%) in low- and middle-income countries. An estimated 1.35 billion (1.34-1.36 billion) people had hypertension in 2010; 349 million (339-359 million) in high-income and 1.00 billion (0.99-1.01 billion) in low- and middle-income countries. From 2000 to 2010, age-standardized prevalence of hypertension decreased by 2.3% in high-income countries but increased by 6.1% in low- and middle-income countries. During the same period, the proportions of awareness (56.6% vs 68.8%), treatment (42.9% vs 56.1%), and control (16.6% vs. 28.9%) increased substantially in high-income countries, whereas awareness (34.7% vs 35.1%), treatment (23.4% vs 26.4%), and control (7.0% vs 7.8%) increased only slightly in low- and middle-income countries. Conclusions: Global disparities in hypertension prevalence, awareness, treatment, and control are large and increasing. Collaborative efforts from national and international stakeholders are urgently needed to combat the emerging hypertension burden in low- and middle-income countries.

These findings suggest that the metabolic syndrome might be an important factor in the cause of chronic kidney disease.

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Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Here we estimated the global prevalence and absolute burden of CKD in 2010 by pooling data from population-based studies. We searched MEDLINE (January 1990 to December 2014), International Society of Nephrology Global Outreach Program funded projects, and bibliographies of retrieved articles and selected 33 studies reporting gender- and age-specific prevalence of CKD in representative population samples. The age standardized global prevalence of CKD stages 1–5 in adults aged 20 and older was 10.4% in men (95% confidence interval 9.3–11.9%) and 11.8% in women (11.2–12.6%). This consisted of 8.6% men (7.3–9.8%) and 9.6% women (7.7–11.1%) in high-income countries, and 10.6% men (9.4–13.1%) and 12.5% women (11.8–14.0%) in low- and middle-income countries. The total number of adults with CKD was 225.7 million (205.7–257.4 million) men and 271.8 million (258.0–293.7 million) women. This consisted of 48.3 million (42.3–53.3 million) men and 61.7 million (50.4–69.9 million) women in high-income countries, and 177.4 million (159.2–215.9 million) men and 210.1 million (200.8–231.7 million) women in low- and middle-income countries. Thus, CKD is an important global-health challenge, especially in low- and middle-income countries. National and international efforts for prevention, detection, and treatment of CKD are needed to reduce its morbidity and mortality worldwide.