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      Serum uromodulin is inversely associated with the metabolic syndrome in the KORA F4 study

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          Abstract

          Objective

          Metabolic syndrome and obesity are risk factors for chronic kidney disease. However, early kidney alterations may escape diagnosis in these conditions due to glomerular hyperfiltration. Uromodulin, a glycoprotein exclusively synthesized in tubular cells of the thick ascending limb of Henle's loop, is a novel tissue-specific biomarker for kidney function. In contrast to the commonly used markers creatinine and cystatin C, serum uromodulin does not primarily depend on glomerular filtration. We hypothesized that serum uromodulin is a marker for metabolic syndrome and related components.

          Design

          The analyses included 1088 participants of the population-based KORA F4 study aged 62–81 years. Metabolic syndrome was present in 554 participants. After a mean follow-up time of 6.5 years, 621 participants were reevaluated, of which 92 had developed incident metabolic syndrome.

          Methods

          The association of serum uromodulin with metabolic syndrome and its components were assessed using multivariable logistic regression models.

          Results

          Serum uromodulin was inversely associated with metabolic syndrome after adjustment for sex, age, estimated glomerular filtration rate, physical activity, smoking, alcohol consumption and high-sensitivity C-reactive protein (OR 0.65; 95% CI 0.56–0.76 per standard deviation uromodulin; P < 0.001). Serum uromodulin was inversely associated with all single components of metabolic syndrome. However, serum uromodulin was not associated with new-onset metabolic syndrome after the follow-up period of 6.5 ± 0.3 years (OR 1.18; 95% CI 0.86–1.60).

          Conclusions

          Serum uromodulin is independently associated with prevalent, but not with incident metabolic syndrome. Low serum uromodulin may indicate a decreased renal reserve in the metabolic syndrome.

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          Most cited references28

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          Metabolic syndrome and risk of cardiovascular disease: a meta-analysis.

          The use of different definitions of the metabolic syndrome has led to inconsistent results on the association between the metabolic syndrome and risk of cardiovascular disease. We examined the association between the metabolic syndrome and risk of cardiovascular disease. A MEDLINE search (1966-April 2005) was conducted to identify prospective studies that examined the association between the metabolic syndrome and risk of cardiovascular disease. Information on sample size, participant characteristics, metabolic syndrome definition, follow-up duration, and endpoint assessment was abstracted. Data from 21 studies met the inclusion criteria and were included. Individuals with the metabolic syndrome, compared to those without, had an increased mortality from all causes (relative risk [RR] 1.35; 95% confidence interval [CI], 1.17-1.56) and cardiovascular disease (RR 1.74; 95% CI, 1.29-2.35); as well as an increased incidence of cardiovascular disease (RR 1.53; 95% CI, 1.26-1.87), coronary heart disease (RR 1.52; 95% CI, 1.37-1.69) and stroke (RR 1.76; 95% CI, 1.37-2.25). The relative risk of cardiovascular disease associated with the metabolic syndrome was higher in women compared with men and higher in studies that used the World Health Organization definition compared with studies that used the Adult Treatment Panel III definition. This analysis strongly suggests that the metabolic syndrome is an important risk factor for cardiovascular disease incidence and mortality, as well as all-cause mortality. The detection, prevention, and treatment of the underlying risk factors of the metabolic syndrome should become an important approach for the reduction of the cardiovascular disease burden in the general population.
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            A systematic review and meta-analysis suggests obesity predicts onset of chronic kidney disease in the general population.

            Obesity and chronic kidney disease (CKD) are public health priorities that share core pathophysiological mechanisms. However, whether high body mass index (BMI) increases risk of CKD de novo remains ill-defined. To evaluate the role of BMI in predicting CKD onset in the general adult population, we performed a systematic review and meta-analysis of PubMed and ISI Web of Science databases articles published between January 2000 and August 2016 without language restriction. We selected studies in adult individuals from a general population with normal renal function at baseline that reported the risk of low estimated glomerular filtration (eGFR) (under 60 mL/min/1.73m(2)) and/or albuminuria (1+ at dipstick or an albumin creatinine ratio of 3.4 mg/mmol or more) as hazard ratio, odds ratio or relative risk related to obesity, overweight, or BMI as continuous value. A total of 39 cohorts covering 630, 677 participants with a mean follow-up of 6.8 years were selected. Obesity increased the relative risk, 95% confidence interval and heterogeneity (I(2)) of developing low eGFR (1.28, 1.07-1.54, [I(2): 95.0%]) and albuminuria (1.51, 1.36-1.67, [I(2): 62.7%]). Increase of BMI unit was also associated with higher risk of low eGFR (1.02, 1.01-1.03, [I(2): 24.3%]) and albuminuria (1.02, 1.00-1.04, [I(2): 0%]). Conversely, overweight did not predict onset of either low eGFR (1.06, 0.94-1.21, [I(2): 50.0%]) or albuminuria (1.24, 0.98-1.58, [I(2): 49.4%]). Thus, a high BMI predicts onset of albuminuria without kidney failure (CKD stages 1-2) as well as CKD stages 3 and higher, the effect being significant only in obese individuals. Hence, our findings may have implications to improve risk stratification and recommendations on body weight control in the general population.
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              Uromodulin: from physiology to rare and complex kidney disorders

              Uromodulin is the most abundant urinary protein. Here, the authors discuss the physiological roles of uromodulin, the mechanisms by which mutations in the UMOD gene, which encodes uromodulin, cause autosomal dominant tubulointerstitial kidney disease and the association of common UMOD variants with complex disorders in the general population.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                October 2019
                10 September 2019
                : 8
                : 10
                : 1363-1371
                Affiliations
                [1 ]Medizinische Klinik und Poliklinik IV , Klinikum der Universität München, LMU München, Munich, Germany
                [2 ]Clinical Cooperation Group Diabetes , LMU München and Helmholtz Zentrum München, Munich, Germany
                [3 ]Freie Waldorfschule Augsburg , Augsburg, Germany
                [4 ]German Center for Diabetes Research (DZD) , München-Neuherberg, Germany
                [5 ]Institute of Epidemiology , Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Neuherberg, Germany
                [6 ]Independent Research Group Clinical Epidemiology , Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Neuherberg, Germany
                [7 ]Chair of Epidemiology at UNIKAT Augsburg , Ludwig-Maximilians-Universität München, Munich, Germany
                [8 ]KORA Study Center , University Hospital Augsburg, Augsburg, Germany
                [9 ]DZHK (German Centre for Cardiovascular Research) , partner site Munich Heart Alliance, Munich, Germany
                [10 ]Institute of Epidemiology and Medical Biometry , University of Ulm, Ulm, Germany
                [11 ]Deutsches Herzzentrum München , Technische Universität München, Munich, Germany
                [12 ]Institute of Biometrics and Epidemiology , German Diabetes Center, Leibniz Institute at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
                [13 ]Institute of Clinical Diabetology , German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
                [14 ]Division of Endocrinology and Diabetology , Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
                [15 ]Klinikum München-Harlaching , Teaching Hospital of the Ludwig-Maximilians-Universität, Munich, Germany
                Author notes
                Correspondence should be addessed to C Then: cornelia.then@ 123456med.uni-muenchen.de
                Article
                EC-19-0352
                10.1530/EC-19-0352
                6790901
                31505464
                5b57867c-da9f-4ae1-bb77-657c2f873941
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 05 September 2019
                : 10 September 2019
                Categories
                Research

                serum uromodulin,uromodulin,sumod,metabolic syndrome,obesity,kidney function

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