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      Associations of Adiponectin with Paraoxonase 1 and sE-Selectin in Hemodialyzed Patients

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          Abstract

          Background/Aims: In hemodialyzed (HD) patients, adiponectin and sE-selectin levels are elevated, while antioxidant paraoxonase 1 activity (PON1) is decreased. We determined if the hyperadiponectinemia in HD patients has a protective effect on the decrease in PON1 and elevation in sE-selectin in kidney failure. Methods and Design: Predialysis serum adiponectin, PON1 and sE-selectin as well as other metabolic variables were measured in 70 HD patients. Results: Adiponectin had (1) no association with PON1 or sE-selectin, (2) a positive association with dialysis efficiency and HDL-C, and (3) an inverse association with BMI, waist circumference, HOMA IR, triglyceride, hsCRP, fibrinogen, and albumin. Moreover, albumin, BMI, and HOMA-IR were independent negative predictors of adiponectin. Conclusions: In kidney failure, in contrast to normal renal function, higher adiponectin levels had no correlation with PON1 activity or the sE-selectin level. However, adiponectin has an association with dialysis efficiency and, similar to individuals with preserved kidney function, traits of metabolic syndrome. In addition to BMI and HOMA-IR, the serum albumin concentration is also one of the independent negative predictors of the serum adiponectin level. Collectively, these findings may add details to the understanding of the role that adiponectin plays in chronic renal disease related to ‘reverse epidemiology’.

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          Atherosclerotic renal artery stenosis: epidemiology, cardiovascular outcomes, and clinical prediction rules.

          Atherosclerotic renal artery stenosis is the most common primary disease of the renal arteries, and it is associated with two major clinical syndromes, ischemic renal disease and hypertension. The prevalence of this disease in the population is undefined because there is no simple and reliable test that can be applied on a large scale. Renal artery involvement in patients with coronary heart disease and/or heart failure is frequent, and it may influence cardiovascular outcomes and survival in these patients. Suspecting renal arterial stenosis in patients with recurrent episodes of pulmonary edema is justified by observations showing that about one third of elderly patients with heart failure display atherosclerotic renal disease. Whether interventions aimed at restoring arterial patency may reduce the high mortality in patients with heart failure is still unclear because, to date, no prospective study has been carried out in these patients. Increased awareness of the need for cost containment has renewed the interest in clinical cues for suspecting renovascular hypertension. In this regard, the DRASTIC study constitutes an important attempt at validating clinical prediction rules. In this study, a clinical rule was derived that predicted renal artery stenosis as efficiently as renal scintigraphy (sensitivity: clinical rule, 65% versus scintigraphy, 72%; specificity: 87% versus 92%). When tested in a systematic and quantitative manner, clinical findings can perform as accurately as more complex tests in the detection of renal artery stenosis.
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            Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with type 2 diabetes.

            Low adiponectin levels, by regulating insulin resistance and metabolic profile, may contribute to the markedly increased risk of atherosclerosis in diabetic subjects. The complex interrelationships between adiponectin and metabolic abnormalities have not yet been fully assessed in diabetic women. We performed a cross-sectional evaluation of the association between circulating adiponectin and glycemia, lipid-lipoprotein levels, and inflammatory markers in 925 women with type 2 diabetes enrolled in the Nurses' Health Study. Circulating adiponectin levels were significantly and positively associated with high-density lipoprotein (HDL) cholesterol and physical activity levels, and inversely with body mass index and plasma concentrations of hemoglobin A1c (HgbA1c), triglycerides, non-HDL cholesterol, apolipoprotein B-100, C-reactive protein, fibrinogen, soluble E-selectin, and soluble intercellular adhesion molecule-1. The above associations were not appreciably altered after adjusting for lifestyle factors, existing medical conditions, obesity, and body fat distribution, with the exception of HgbA1c and soluble intercellular adhesion molecule-1 (which became nonsignificant). Associations between adiponectin and inflammatory markers persisted after control for the potential confounding effects of HgbA1C and HDL cholesterol, suggesting that the antiinflammatory properties of adiponectin are not mediated by its effect on glycemia and lipidemia. With the exception of the associations with triglycerides and apolipoprotein B100, which were significant only in subjects with body mass index less than 30, all other associations observed herein were consistent among obese and nonobese diabetic women. In summary, higher adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in diabetic women.
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              Adiponectin in chronic kidney disease is related more to metabolic disturbances than to decline in renal function.

              Adiponectin, a newly discovered collagen-like protein of the collectin family exclusively produced by adipocytes, possesses anti-inflammatory properties. Plasma adiponectin is associated with a decreased cardiovascular risk in non-renal patients, and is reduced in obesity and insulin-resistant states. Although reports show an increase in the adiponectin level in maintenance haemodialysis, peritoneal dialysis and end-stage renal disease, there is no documentation of adiponectin levels and regulation in the early stages of chronic kidney disease (CKD). We prospectively measured glomerular filtration rate (GFR) in 48 patients with CKD using inulin clearance. Fasting blood was drawn to determine insulin, leptin, adiponectin and C-reactive protein (CRP) levels. Body fat mass was calculated using skinfold thickness measurements. The patients' mean GFR was 53.5+/-24.9 (SD) ml/min/1.73 m2. Adiponectin was in the normal range in men (9.8+/-2.9 mg/l) and women (16.6+/-5.0 mg/l) with CKD, being significantly higher in women than men (P<0.001). Serum leptin was above normal (10.4+/-10.7 microg/l), whereas serum insulin and CRP were within their normal ranges (3.5+/-3.3 microU/ml and 2.6+/-5.0 mg/l, respectively). In linear regression analysis, adiponectin was negatively correlated with GFR (P = 0.02), fat mass (P = 0.03) and body mass index (P = 0.002), and strongly positively correlated with serum leptin (P = 0.003). A positive relationship was also found between plasma adiponectin and the urinary albumin/creatinine ratio (P = 0.007). No relationship was found between adiponectin and insulin or adiponectin and CRP. In multiple regression analysis, adiponectin was significantly positively correlated with leptin (P<0.0001), negatively with body mass index (P<0.0001) and only weakly with GFR (P = 0.04). Despite an adverse metabolic environment in chronic renal insufficiency, serum adiponectin increases in non-obese patients when renal function deteriorates. Adiponectin is only weakly affected by renal function per se, but appears influenced by proteinuria, and more significantly by body mass index and the change in serum leptin that accompanies decline in renal function.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2009
                November 2009
                03 November 2009
                : 32
                : 5
                : 360-365
                Affiliations
                aInstitute of Laboratory Medicine and b1st Department of Medicine, School of Medicine, University of Pecs, cFMC Dialysis Center, Pecs, d1st Department of Medicine, University of Debrecen, Medical and Health Science Center, Debrecen, and eMEDIPOLIS Knowledge Center, Pecs, Hungary
                Article
                254335 Kidney Blood Press Res 2009;32:360–365
                10.1159/000254335
                19887823
                37c118d7-1ffc-4012-875f-aab903c66eeb
                © 2009 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
                : 21 April 2009
                : 01 September 2009
                Page count
                Tables: 4, References: 22, Pages: 6
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Insulin resistance,Hemodialysis,Soluble E-selectin,Serum paraoxonase 1,Adiponectin

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