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      Role of Uremic Toxins in Early Vascular Ageing and Calcification

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          Abstract

          In patients with advanced chronic kidney disease (CKD), the accumulation of uremic toxins, caused by a combination of decreased excretion secondary to reduced kidney function and increased generation secondary to aberrant expression of metabolite genes, interferes with different biological functions of cells and organs, contributing to a state of chronic inflammation and other adverse biologic effects that may cause tissue damage. Several uremic toxins have been implicated in severe vascular smooth muscle cells (VSMCs) changes and other alterations leading to vascular calcification (VC) and early vascular ageing (EVA). The above mentioned are predominant clinical features of patients with CKD, contributing to their exceptionally high cardiovascular mortality. Herein, we present an update on pathophysiological processes and mediators underlying VC and EVA induced by uremic toxins. Moreover, we discuss their clinical impact, and possible therapeutic targets aiming at preventing or ameliorating the harmful effects of uremic toxins on the vasculature.

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          Most cited references201

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          Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

          Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding Bill & Melinda Gates Foundation.
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            Dapagliflozin in Patients with Chronic Kidney Disease

            Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.
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              Clinical epidemiology of cardiovascular disease in chronic renal disease.

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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                03 January 2021
                January 2021
                : 13
                : 1
                : 26
                Affiliations
                [1 ]One Health Research Group, Faculty of Medicine, Universidad de Las Américas (UDLA), Antigua Vía a Nayón, Quito EC170124, Ecuador; nikolaos.kyriakidis@ 123456udla.edu.ec
                [2 ]Nephrology Department, Hospital de Especialidades Eugenio Espejo, Av. Yahuachi s/n, Quito EC170403, Ecuador; gabriela.cobo@ 123456hee.gob.ec
                [3 ]Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Huddinge, 141 86 Stockholm, Sweden; lu.dai@ 123456ki.se (L.D.); bengt.lindholm@ 123456ki.se (B.L.)
                Author notes
                [* ]Correspondence: peter.stenvinkel@ 123456ki.se
                [†]

                Both authors have contributed equally.

                Author information
                https://orcid.org/0000-0003-1382-5661
                https://orcid.org/0000-0001-6930-4174
                https://orcid.org/0000-0001-9036-3857
                https://orcid.org/0000-0003-4269-4293
                Article
                toxins-13-00026
                10.3390/toxins13010026
                7824162
                33401534
                17881197-280e-409a-9ff6-af8b18831c99
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 December 2020
                : 28 December 2020
                Categories
                Review

                Molecular medicine
                chronic kidney disease,uremic toxins,vascular calcification,cardiovascular disease,vascular smooth muscle cells

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