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      Circulating CD5L is associated with cardiovascular events and all-cause mortality in individuals with chronic kidney disease

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          Abstract

          This study assessed the association of CD5L and soluble CD36 (sCD36) with the risk of a cardiovascular event (CVE), including CV death and all-cause mortality in CKD. We evaluated the association of CD5L and sCD36 with a predefined composite CV endpoint (unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular accident, congestive heart failure, arrhythmia, peripheral arterial disease [PAD] or amputation by PAD, aortic aneurysm, or death from CV causes) and all-cause mortality using Cox proportional hazards regression, adjusted for CV risk factors. The analysis included 1,516 participants free from pre-existing CV disease followed up for 4 years. The median age was 62 years, 38.8% were female, and 26.8% had diabetes. There were 98 (6.5%) CVEs and 72 (4.8%) deaths, of which 26 (36.1%) were of CV origin. Higher baseline CD5L concentration was associated with increased risk of CVE (HR, 95% CI, 1.17, 1.0–1.36), and all-cause mortality (1.22, 1.01–1.48) after adjusting for age, sex, diabetes, systolic blood pressure, dyslipidemia, waist circumference, smoking, and CKD stage. sCD36 showed no association with adverse CV outcomes or mortality. Our study showed for the first time that higher concentrations of CD5L are associated with future CVE and all-cause mortality in individuals with CKD.

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          Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.

          End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined. We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization. The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m2 (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m2 (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m2 (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern. An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency. Copyright 2004 Massachusetts Medical Society
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            A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation

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              Kidney disease and increased mortality risk in type 2 diabetes.

              Type 2 diabetes associates with increased risk of mortality, but how kidney disease contributes to this mortality risk among individuals with type 2 diabetes is not completely understood. Here, we examined 10-year cumulative mortality by diabetes and kidney disease status for 15,046 participants in the Third National Health and Nutrition Examination Survey (NHANES III) by linking baseline data from NHANES III with the National Death Index. Kidney disease, defined as urinary albumin/creatinine ratio ≥30 mg/g and/or estimated GFR ≤60 ml/min per 1.73 m(2), was present in 9.4% and 42.3% of individuals without and with type 2 diabetes, respectively. Among people without diabetes or kidney disease (reference group), 10-year cumulative all-cause mortality was 7.7% (95% confidence interval [95% CI], 7.0%-8.3%), standardized to population age, sex, and race. Among individuals with diabetes but without kidney disease, standardized mortality was 11.5% (95% CI, 7.9%-15.2%), representing an absolute risk difference with the reference group of 3.9% (95% CI, 0.1%-7.7%), adjusted for demographics, and 3.4% (95% CI, -0.3% to 7.0%) when further adjusted for smoking, BP, and cholesterol. Among individuals with both diabetes and kidney disease, standardized mortality was 31.1% (95% CI, 24.7%-37.5%), representing an absolute risk difference with the reference group of 23.4% (95% CI, 17.0%-29.9%), adjusted for demographics, and 23.4% (95% CI, 17.2%-29.6%) when further adjusted. We observed similar patterns for cardiovascular and noncardiovascular mortality. In conclusion, those with kidney disease predominantly account for the increased mortality observed in type 2 diabetes.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                15 October 2021
                10 October 2021
                : 13
                : 19
                : 22690-22709
                Affiliations
                [1 ]Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau and Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona 08041, Spain
                [2 ]Department of Internal Medicine, Endocrinology, Metabolism and Lipid Research Division, Washington University School of Medicine, St Louis, MO 63110, USA
                [3 ]Institute for Health Science Research Germans Trias i Pujol (IGTP) and Center for Biomedical Research on Liver and Digestive Diseases (CIBEREHD), Madrid 28029, Spain
                [4 ]Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida, (IRBLleida), Lleida 25198, Spain
                [5 ]Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Badalona 08916, Spain
                [6 ]B2SLab, Department of Systems Engineering, Automation and Industrial Informatics, Polytechnic University of Catalonia, Barcelona 08034, Spain
                [7 ]DAP-Cat Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona 08006, Spain
                [8 ]Department of Medicine, Barcelona Autonomous University (UAB), Bellaterra 08193, Spain
                [9 ]Primary Health Care Center Raval Sud, Gerència d’Atenció Primaria, Institut Català de la Salut, Barcelona 08001, Spain
                [10 ]Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki 00290, Finland
                [11 ]Abdominal Center Nephrology, University of Helsinki and Helsinki University Central Hospital, Helsinki 00280, Finland
                [12 ]Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki 00100, Finland
                [13 ]Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia
                [14 ]Faculty of Medicine, University of Vic – Central University of Catalonia (UVic/UCC), Vic 08500, Spain
                [15 ]Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona 08907, Spain
                Author notes
                Correspondence to: Núria Alonso; email: nalonso.germanstrias@gencat.cat
                Correspondence to: Didac Mauricio; email: didacmauricio@gmail.com, https://orcid.org/0000-0002-2868-0250
                Article
                203615 203615
                10.18632/aging.203615
                8544330
                34629330
                bfb9db9b-4415-44d9-94e8-f5a5e31d632b
                Copyright: © 2021 Castelblanco et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 April 2021
                : 29 September 2021
                Categories
                Research Paper

                Cell biology
                cd5l,scd36,chronic kidney disease,cardiovascular events,mortality
                Cell biology
                cd5l, scd36, chronic kidney disease, cardiovascular events, mortality

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