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      Effect of increased water intake on plasma copeptin in patients with chronic kidney disease: results from a pilot randomised controlled trial

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          Abstract

          Objectives

          Increased water intake may have a beneficial effect on the kidney through suppression of plasma vasopressin. We examined the effect of increased water intake on plasma copeptin (a marker of vasopressin) over 6 weeks in patients with chronic kidney disease.

          Design

          Secondary analysis of a randomised controlled parallel-group pilot trial.

          Setting

          Canada, 2012–2013.

          Participants

          28 patients with stage 3 chronic kidney disease randomised (2:1) to a hydration (n=17) or control group (n=11).

          Intervention

          The hydration group was coached to increase water intake by up to 1.5 L/day for 6 weeks. The control group was asked to maintain regular water intake.

          Measures and outcomes

          Participants provided blood and 24 h urine samples at baseline and 6 weeks. Change in plasma copeptin was compared within and between study groups.

          Results

          Participants were 64% male with a mean age of 62 years and an estimated glomerular filtration rate of 40 mL/min/1.73 m 2. Between baseline and 6 weeks, 24 h urine volume increased by 0.7 L/day in the hydration group, rising from 2.3 to 3.0 L/day (p=0.01), while decreasing by 0.3 L/day among controls, from 2.0 to 1.7 L/day (p=0.07); between-group difference: 0.9 L/day (95% CI 0.37 to 1.46; p=0.002). In the hydration group, median copeptin decreased by 3.6 pmol/L, from 15.0 to 10.8 pmol/L (p=0.005), while remaining stable among controls at 19 pmol/L (p=0.76; p=0.19 for the between-group difference in median change); the between-group difference in mean change was 5.4 pmol/L (95% CI −1.2 to 12.0; p=0.11).

          Conclusions

          Adults with stage 3 chronic kidney disease can be successfully randomised to drink approximately 1 L more per day than controls. This increased water intake caused a significant decrease in plasma copeptin concentration. Our larger 12-month trial will examine whether increased water intake can slow renal decline in patients with chronic kidney disease.

          Trial registration number

          NCT01753466.

          Related collections

          Most cited references 39

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          Recommendations for planning pilot studies in clinical and translational research.

          Advances in clinical and translation science are facilitated by building on prior knowledge gained through experimentation and observation. In the context of drug development, preclinical studies are followed by a progression of phase I through phase IV clinical trials. At each step, the study design and statistical strategies are framed around research questions that are prerequisites for the next phase. In other types of biomedical research, pilot studies are used for gathering preliminary support for the next research step. However, the phrase "pilot study" is liberally applied to projects with little or no funding, characteristic of studies with poorly developed research proposals, and usually conducted with no detailed thought of the subsequent study. In this article, we present a rigorous definition of a pilot study, offer recommendations for the design, analysis and sample size justification of pilot studies in clinical and translational research, and emphasize the important role that well-designed pilot studies play in the advancement of science and scientific careers. © 2011 Wiley Periodicals, Inc.
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            Fluid and nutrient intake and risk of chronic kidney disease.

            We evaluated the association between fluid and nutrient intake and chronic kidney disease (CKD). Two cross-sectional population-based studies. Validated nutrition food frequency questionnaires (FFQ) administered to people >50 years, identified in a door-to-door census of a well-defined suburban area. Based upon nutrition tables we calculated intakes of over 40 nutrients (factors) and total daily energy intake. Primary outcome was CKD. Fluid (total content of fluid and drinks assessed in the FFQ) and nutrient intake was stratified in quintiles and association with CKD analysed by logistic regression, expressed as unadjusted and adjusted odds ratios, with testing for linear trend. The proportion of participants who completed the FFQ and had glomerular filtration rate (GFR) measures was 2744/3654 (75.0%) for the first and 2476/3508 (70.6%) for the second survey. CKD was present in 12.4-23.5% men and 14.9-28.7% women (mean ages 66.4-65.4 years), respectively. Participants who had the highest quintile of fluid intake (3.2 L/day) had a significantly lower risk of CKD (odds ratio 0.5, 95%CI 0.32 to 0.77, P for trend = 0.003). These findings were consistent across both study periods, both equations to calculate GFR and both GFR thresholds. Higher intakes of fluid appear to protect against CKD. CKD may be preventable at a population level with low-cost increased fluid intake. © 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.
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              Incremental value of copeptin for rapid rule out of acute myocardial infarction.

              The purpose of this study was to examine the incremental value of copeptin for rapid rule out of acute myocardial infarction (AMI). The rapid and reliable exclusion of AMI is a major unmet clinical need. Copeptin, the C-terminal part of the vasopressin prohormone, as a marker of acute endogenous stress may be useful in this setting. In 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, we measured levels of copeptin at presentation, using a novel sandwich immunoluminometric assay in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists using all available data. The adjudicated final diagnosis was AMI in 81 patients (17%). Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses (median 20.8 pmol/l vs. 6.0 pmol/l, p < 0.001). The combination of troponin T and copeptin at initial presentation resulted in an area under the receiver-operating characteristic curve of 0.97 (95% confidence interval: 0.95 to 0.98), which was significantly higher than the 0.86 (95% confidence interval: 0.80 to 0.92) for troponin T alone (p < 0.001). A copeptin level <14 pmol/l in combination with a troponin T < or =0.01 microg/l correctly ruled out AMI with a sensitivity of 98.8% and a negative predictive value of 99.7%. The additional use of copeptin seems to allow a rapid and reliable rule out of AMI already at presentation and may thereby obviate the need for prolonged monitoring and serial blood sampling in the majority of patients. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587).
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2015
                24 November 2015
                : 5
                : 11
                Affiliations
                [1 ]Division of Nephrology, Department of Medicine, London Health Sciences Centre , London, Ontario, Canada
                [2 ]Department of Epidemiology & Biostatistics, Western University , London, Ontario, Canada
                Author notes
                [Correspondence to ] Dr William F Clark; William.Clark@ 123456lhsc.on.ca
                Article
                bmjopen-2015-008634
                10.1136/bmjopen-2015-008634
                4663439
                26603245
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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                Renal Medicine
                Research
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