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      Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

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          Abstract

          Background: Our aim was to test if plasma copeptin, a stable surrogate marker of arginine vasopressin, predicts decline of glomerular filtration rate (GFR) and risk of chronic kidney disease (CKD). Methods: We measured copeptin and renal function at the Malmö Diet and Cancer Cardiovascular Cohort baseline exam and reassessed renal function after a follow-up time of 16.6 ± 1.5 years (n = 3,186). Furthermore, we defined CKD based on an estimated GFR (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) <60 (CKD_60<sub>MDRD</sub>), <45 (CKD_45<sub>MDRD</sub>) and <30 (CKD_30<sub>MDRD</sub>) ml/min/1.73 m<sup>2</sup>. Results: After multivariate adjustment (gender, age, baseline eGFR, smoking status, systolic blood pressure, antihypertensive treatment and follow-up time), copeptin (beta-coefficient per 1 SD increment of copeptin) was independently associated with significantly greater annual decline of eGFR (ml/min/1.73 m<sup>2</sup>) according to the MDRD formula (OR 0.057, 95% CI 0.022-0.093; p = 0.001) as well as according to the CKD Epidemiology Collaboration (CKD-EPI) formula (OR 0.050, 95% CI 0.022-0.077; p < 0.001). Each SD increment of copeptin independently predicted incident CKD_60<sub>MDRD</sub> (OR 1.19, 95% CI 1.04-1.36; p = 0.010), CKD_45<sub>MDRD</sub> (OR 1.33, 95% CI 1.04-1.71; p = 0.026) and CKD_30<sub>MDRD</sub> (OR 3.69, 95% CI 1.41-9.66; p = 0.008). The relationship between copeptin and CKD defined by CKD-EPI gave similar results. Conclusion: Our data suggest that increased levels of copeptin independently predict decline in eGFR and greater risk of new-onset CKD.

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          Plasma copeptin, a unifying factor behind the metabolic syndrome.

          Arginine vasopressin (AVP) is known to affect liver glycogenolysis, insulin, and glucagon secretion and pituitary ACTH release. We previously showed that high copeptin, the stable C-terminal fragment of AVP prohormone, is independently associated with hyperinsulinemia and future development of diabetes mellitus. The objective of the study was to examine whether plasma copeptin is associated with components of the metabolic syndrome (MetS) independently of insulin, diabetes mellitus, and environmental factors. This was a cross-sectional, population-based sample of 4742 subjects, aged 46-68 yr, 60% women, in Malmö, Sweden. Using multivariable logistic and linear regression, plasma copeptin was associated with components of the MetS. Copeptin quartile (lowest quartile as reference) was, after adjustment for age, sex, insulin, and diabetes mellitus, associated with hypertension (odds ratios 1.04, 1.07, 1.31; P = 0.004), abdominal obesity (odds ratios 1.21, 1.16, 1.57; P = 0.002), obesity (odds ratios 1.25, 1.15, 1.49; P = 0.01), top quartile of c-reactive protein (odds ratios 1.11, 1.13, 1.32; P = 0.007), and MetS (adjusted for age and sex only) (odds ratios 1.53, 1.77, 1.86; P < 0.001). High copeptin levels were significantly associated with high fat intake, low physical activity, and borderline significantly associated with low socioeconomic status. The association between copeptin and components of the MetS was not affected after adjustment for these environmental factors. Our data suggest that increased activity of the AVP system is a unifying factor in the MetS and point to a new pharmacologically modifiable system of potential importance in the treatment of MetS and prevention of cardiovascular disease.
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            Effect of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease by CKD Stage: Results from the TEMPO 3:4 Trial.

            and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of kidney growth and eGFR decline in autosomal dominant polycystic kidney disease (ADPKD). This post hoc analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline.
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              Incident coronary events and case fatality in relation to common carotid intima-media thickness.

              To evaluate the incidence of coronary events (CE) and case fatality in relation to common carotid intima-media thickness (IMT) and carotid plaque over a median follow up of 7 years. A total of 5163 Swedish middle-aged men and women with no prior myocardial infarction and/or stroke. The associations amongst B-mode ultrasound determined common carotid IMT, carotid plaque (focal IMT > 1.2 mm) and carotid stenosis (lumen reduction of >15%) and incident CE, were investigated in relation to cardiovascular risk factor levels. Age- and sex-adjusted common carotid IMT, carotid plaque and carotid stenosis were significantly (P < 0.05) related to future CE. Adjustment for established risk factors generally reduced the hazard rate ratios. However, the continuous measure of common carotid IMT, carotid plaque and carotid stenosis were significantly related to incident CE, even after risk factor adjustment. The strength of the associations between common carotid IMT and CE was only to a small extent reduced after adjustment for presence of carotid plaque. There were no statistically significant associations between common carotid IMT, carotid plaque or carotid stenosis and short-term case-fatality rates (28-days mortality) or long-term case-fatality rates (5-years mortality). The results show an association between common carotid IMT and incident CE, independently of cardiovascular risk factors and carotid plaque. However, there was no association with short-term or long-term mortality after a CE.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2016
                July 2016
                28 June 2016
                : 44
                : 1
                : 22-28
                Affiliations
                Departments of aInternal Medicine and bNephrology, Skåne University Hospital, Departments of cClinical Sciences and dNephrology, Lund University, Malmö, Sweden
                Author notes
                *Irina Tasevska, Department of Internal Medicine, Skåne University Hospital, SE-20502 Malmö (Sweden), E-Mail tasevskairina@gmail.com
                Article
                447522 Am J Nephrol 2016;44:22-28
                10.1159/000447522
                27347674
                991f6dac-6a24-4e3e-9bfe-b87fe2c123ce
                © 2016 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 20 January 2016
                : 07 June 2016
                Page count
                Figures: 1, Tables: 4, References: 20, Pages: 7
                Categories
                Original Report: Patient-Oriented, Translational Research

                Cardiovascular Medicine,Nephrology
                Epidemiology,Copeptin,Chronic kidney disease,Estimated glomerular filtration rate

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