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      Low serum sodium is associated with protein energy wasting and increased interdialytic weight gain in haemodialysis patients

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          Abstract

          Background

          Low serum sodium (Na) has been associated with decreased body mass index and increased cardiovascular mortality in haemodialysis (HD) patients. We examined the relationship between serum Na and selected nutritional parameters of protein energy wasting that are not affected from the hydration status in a cohort of HD patients.

          Methods

          Triceps skinfold thickness (TSF), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), handgrip strength (HGS) and subjective global assessment (SGA) were assessed in maintenance HD patients using standard techniques. MAMC was calculated with the formula MAMC (cm) = MAC (cm) −3.142 × TSF cm. Pre-dialysis serum Na values from routine monthly laboratory measurements were averaged for the last 6 months prior to the nutritional assessment.

          Results

          Altogether 172 patients with anthropometric data were included in the final analysis. Mean age was 66 ± 14, females 62 (36%) and diabetics 48 (28.9%). Patients with pre-dialysis serum Na below the mean value (136.2 mEq/L) had lower MAMC, HGS, SGA scores and albumin levels (23.50 ± 3.16 cm versus 24.58 ± 3.71 cm, P = 0.048; 21.7 ± 13.6 kg versus 28.0 ± 12.4 kg, P = 0.030; 5.1 ± 1.2 versus 5.7 ± 1.0, P = 0.012 and 31.65 ± 4.73 mg/L versus 32.25 ± 3.91 mg/L, P = 0.022, respectively) and higher interdialytic weight gains. Pre-dialysis serum Na correlated positively with MAMC, handgrip and SGA (Pearson's correlation r = 0.165, P = 0.031, r = 0.237, P = 0.022 and r = 0.195, P = 0.011, respectively).

          Conclusion

          This study demonstrates that low serum sodium is associated with protein energy wasting and increased interdialytic weight gain in HD patients.

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          Most cited references19

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          Fluid retention is associated with cardiovascular mortality in patients undergoing long-term hemodialysis.

          Patients with chronic kidney disease (stage 5) who undergo hemodialysis treatment have similarities to heart failure patients in that both populations retain fluid frequently and have excessively high mortality. Volume overload in heart failure is associated with worse outcomes. We hypothesized that in hemodialysis patients, greater interdialytic fluid gain is associated with poor all-cause and cardiovascular survival. We examined 2-year (July 2001 to June 2003) mortality in 34,107 hemodialysis patients across the United States who had an average weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent hemodialysis treatment started. The 3-month averaged interdialytic weight gain was divided into 8 categories of 0.5-kg increments (up to > or =4.0 kg). Eighty-six percent of patients gained >1.5 kg between 2 dialysis sessions. In unadjusted analyses, higher weight gain was associated with better nutritional status (higher protein intake, serum albumin, and body mass index) and tended to be linked to greater survival. However, after multivariate adjustment for demographics (case mix) and surrogates of malnutrition-inflammation complex, higher weight-gain increments were associated with increased risk of all-cause and cardiovascular death. The hazard ratios (95% confidence intervals) of cardiovascular death for weight gain or =4.0 kg (compared with 1.5 to 2.0 kg as the reference) were 0.67 (0.58 to 0.76) and 1.25 (1.12 to 1.39), respectively. In hemodialysis patients, greater fluid retention between 2 subsequent hemodialysis treatment sessions is associated with higher risk of all-cause and cardiovascular death. The mechanisms by which fluid retention influences cardiovascular survival in hemodialysis may be similar to those in patients with heart failure and warrant further research.
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            Prevention of angiotensin II-mediated renal oxidative stress, inflammation, and fibrosis by angiotensin-converting enzyme 2.

            Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase capable of metabolizing angiotensin (Ang) II into Ang 1 to 7. We hypothesized that ACE2 is a negative regulator of Ang II signaling and its adverse effects on the kidneys. Ang II infusion (1.5 mg/kg⁻¹/d⁻¹) for 4 days resulted in higher renal Ang II levels and increased nicotinamide adenine dinucleotide phosphate oxidase activity in ACE2 knockout (Ace2(-/y)) mice compared to wild-type mice. Expression of proinflammatory cytokines, interleukin-1β and chemokine (C-C motif) ligand 5, were increased in association with greater activation of extracellular-regulated kinase 1/2 and increase of protein kinase C-α levels. These changes were associated with increased expression of fibrosis-associated genes (α-smooth muscle actin, transforming growth factor-β, procollagen type Iα1) and increased protein levels of collagen I with histological evidence of increased tubulointerstitial fibrosis. Ang II-infused wild-type mice were then treated with recombinant human ACE2 (2 mg/kg⁻¹/d⁻¹, intraperitoneal). Daily treatment with recombinant human ACE2 reduced Ang II-induced pressor response and normalized renal Ang II levels and oxidative stress. These changes were associated with a suppression of Ang II-mediated activation of extracellular-regulated kinase 1/2 and protein kinase C pathway and Ang II-mediated renal fibrosis and T-lymphocyte-mediated inflammation. We conclude that loss of ACE2 enhances renal Ang II levels and Ang II-induced renal oxidative stress, resulting in greater renal injury, whereas recombinant human ACE2 prevents Ang II-induced hypertension, renal oxidative stress, and tubulointerstitial fibrosis. ACE2 is an important negative regulator of Ang II-induced renal disease and enhancing ACE2 action may have therapeutic potential for patients with kidney disease.
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              Hyponatremia and Inflammation: The Emerging Role of Interleukin-6 in Osmoregulation

              Although hyponatremia is a recognized complication of several inflammatory diseases, its pathophysiology in this setting has remained elusive until recently. A growing body of evidence now points to an important role for interleukin-6 in the non-osmotic release of vasopressin. Here, we review this evidence by exploring the immuno-neuroendocrine pathways connecting interleukin-6 with vasopressin. The importance of these connections extends to several clinical scenarios of hyponatremia and inflammation, including hospital-acquired hyponatremia, postoperative hyponatremia, exercise-associated hyponatremia, and hyponatremia in the elderly. Besides insights in pathophysiology, the recognition of the propensity for antidiuresis during inflammation is also important with regard to monitoring patients and selecting the appropriate intravenous fluid regimen, for which recommendations are provided.
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                Author and article information

                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                ndtplus
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                April 2014
                20 January 2014
                20 January 2014
                : 7
                : 2
                : 156-160
                Affiliations
                [1 ]Renal and Transplantation Unit, St George's Hospital NHS Trust , London, UK
                [2 ]Cardiovascular Sciences Research Centre, St. George's University of London , London, UK
                Author notes
                Correspondence and offprint requests to: Dimitrios Poulikakos; E-mail: dimitrios.poulikakos@ 123456stgeorges.nhs.uk
                Article
                sft170
                10.1093/ckj/sft170
                4377774
                25852864
                efd80934-cfae-4d8c-a00b-cf6fbed41d43
                © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For permissions, please email: journals.permissions@oup.com.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 28 October 2013
                : 20 December 2013
                Page count
                Pages: 5
                Categories
                Original Contributions
                Clinical Research

                Nephrology
                hyponatraemia,interdialytic weight gain,malnutrition,mamc,thirst
                Nephrology
                hyponatraemia, interdialytic weight gain, malnutrition, mamc, thirst

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