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      Association between Arterial Stiffness and Peritoneal Fluid Kinetics

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          Abstract

          Background: A high peritoneal transport status in continuous ambulatory peritoneal dialysis (CAPD) patients is associated with a markedly increased morbidity and mortality. While the causes are as yet unknown, overall the proportion of deaths due to cardiovascular disease is estimated at 40–50% among dialysis patients. Arterial stiffness has been established as a cardiovascular risk factor, while the links between peritoneal transport status and aortic stiffness have not yet been investigated. Methods: We included 65 prevalent CAPD patients (24 males/41 females) from our center in a cross-sectional study. Arterial stiffness was assessed by brachial pulse pressure (PP) and carotid-femoral pulse wave velocity (C-F PWV). The patients’ peritoneal fluid transport was assessed by kinetic modeling. The patients’ peritoneal small solute transport rate was assessed by D/P<sub>cr</sub> at 4 h. Extracellular water to total body water (E/T) ratio was assessed by means of bioimpedance analysis. C-reactive protein was also measured. Results: C-F PWV was positively correlated with patients’ age (r = 0.489, p < 0.01), diabetic status (r = 0.327, p < 0.01), peritoneal fluid absorption rate (Ke; r = 0.251, p < 0.05), PP (r = 0.483, p < 0.01), and E/T (r = 0.517, p < 0.01). Multivariate regression analysis showed that C-F PWV was independently related to E/T (p < 0.01), PP (p < 0.01), age (p < 0.05), and Ke (p < 0.05). Conclusion: Peritoneal fluid transport (Ke), as well as E/T, age and PP were found to be independent predictors of elevated C-F PWV in CAPD patients, suggesting that there might be a link between high aortic stiffness and increased Ke rate, hypothetically through generalized vasculopathy.

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          Most cited references14

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          Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure.

          Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality. One hundred and nine predialysis patients (age 52 +/- 1 years) with terminal CRF (glomerular filtration rate 7 +/- 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-alpha (TNF-alpha; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined. Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 +/- 0.6 vs. 13.2 +/- 0.7 mm2, P or = 10 mg/liter). Malnourished patients had higher CRP levels (23 +/- 3 vs. 13 +/- 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 +/- 0.8 vs. 16.9 +/- 0.7 mm2, P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model. These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques.
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            Cardiac and arterial interactions in end-stage renal disease.

            Although cardiac hypertrophy is a frequent complication of end-stage renal disease (ESRD), relatively little is known about large arterial geometry and function in vivo in these patients, and the relationship between arterial changes and cardiac hypertrophy is unknown. Common carotid artery (CCA) intima-media thickness and internal diameter and left ventricular geometry and function were determined by ultrasound imaging in 70 uncomplicated ESRD patients and in 50 age-, sex-, and blood pressure-matched controls. Arterial distensibility and compliance were determined from simultaneously recorded CCA diameter and stroke changes in diameter and CCA pressure waveforms, obtained by applanation tonometry, and also by the measurement of carotid-femoral pulse wave velocity. Compared with control subjects, ESRD patients had greater left ventricular diameter (P < 0.01), wall thicknesses and mass (P < 0.001), increased CCA diameter (6.25 +/- 0.87 vs. 5.55 +/- 0.65 mm; P < 0.001), larger CCA intima-media thickness (777 +/- 115 vs. 678 +/- 105 microns; P < 0.001) and intima-media cross-sectional area (17.5 +/- 4.5 vs. 13.4 +/- 3.3 mm2; P < 0.001). In uremic patients, arterial hypertrophy was associated with decreased CCA distensibility (17.8 +/- 8.8 vs. 24.0 +/- 12.7 kPa-1.10(-3); P < 0.001) and compliance (5.15 +/- 2 vs. 6.0 +/- 2.5 m2.kPa-1.10(-7); P < 0.05), accelerated carotid-femoral pulse wave velocity (1055 +/- 290 vs. 957 +/- 180 cm/seconds; P < 0.001), early return and increased effect of arterial wave reflections (20.5 +/- 15.4 vs. 9.2 +/- 18.4%; P < 0.001). The latter phenomenons were responsible for increased pulsatile pressure load in CCA (58.3 +/- 21 vs. 48 +/- 17 mm Hg; P < 0.01) and were associated with a decreased subendocardial viability index (157 +/- 31 vs. 173 +/- 30%; P < 0.001). The CCA diameter was correlated with the left ventricular diameter (P < 0.01), and a significant correlations existed between CCA wall thickness or CCA intima-media cross-sectional area and left ventricular wall thicknesses and/or left ventricular mass (P < 0.01). In multivariate analysis, these relationships were independent regarding age, sex, blood pressure and body surface area. The present study documents parallel cardiac and vascular adaptation in ESRD, and demonstrates the potential contribution of structural and functional large artery alterations to the pathogenesis of left ventricular hypertrophy and functional alterations.
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              Aquaporin water channels and endothelial cell function.

              The aquaporins (AQP) are a family of homologous water channels expressed in many epithelial and endothelial cell types involved in fluid transport. AQP1 protein is strongly expressed in most microvascular endothelia outside of the brain, as well as in endothelial cells in cornea, intestinal lacteals, and other tissues. AQP4 is expressed in astroglial foot processes adjacent to endothelial cells in the central nervous system. Transgenic mice lacking aquaporins have been useful in defining their role in mammalian physiology. Mice lacking AQP1 manifest defective urinary concentrating ability, in part because of decreased water permeability in renal vasa recta microvessels. These mice also show a defect in dietary fat processing that may involve chylomicron absorption by intestinal lacteals, as well as defective active fluid transport across the corneal endothelium. AQP1 might also play a role in tumour angiogenesis and in renal microvessel structural adaptation. However, AQP1 in most endothelial tissues does not appear to have a physiological function despite its role in osmotically driven water transport. For example, mice lacking AQP1 have low alveolar-capillary water permeability but unimpaired lung fluid absorption, as well as unimpaired saliva and tear secretion, aqueous fluid outflow, and pleural and peritoneal fluid transport. In the central nervous system mice lacking AQP4 are partially protected from brain oedema in water intoxication and ischaemic models of brain injury. Therefore, although the role of aquaporins in epithelial fluid transport is in most cases well-understood, there remain many questions about the role of aquaporins in endothelial cell function. It is unclear why many leaky microvessels strongly express AQP1 without apparent functional significance. Improved understanding of aquaporin-endothelial biology may lead to novel therapies for human disease, such as pharmacological modulation of corneal fluid transport, renal fluid clearance and intestinal absorption.
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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
                2008
                November 2007
                17 October 2007
                : 28
                : 1
                : 128-132
                Affiliations
                Division of Nephrology, Peking University Third Hospital, Beijing, China
                Article
                109981 Am J Nephrol 2008;28:128–132
                10.1159/000109981
                17943019
                d7daf0a7-aae7-4e27-af1e-5844b79318bb
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. 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
                : 04 April 2007
                : 21 August 2007
                Page count
                Tables: 3, References: 30, Pages: 5
                Categories
                Original Report: Patient-Oriented, Translational Research

                Cardiovascular Medicine,Nephrology
                Absorption rate, peritoneal fluid,Arterial stiffness,Peritoneal dialysis

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