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      Effect of Nutritional Status on Human Paraoxonase-1 Activity in Patients with Chronic Kidney Disease

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          Abstract

          Background/Methods: The association between nutritional status, antioxidant human paraoxonase-1 (PON1) activity and low grade inflammation in hemodialized (HD) patients with chronic kidney disease (CKD) is unclear. The aim of this study was to determine PON1 paraoxonase and lactonase activities, ADMA, adiponectin and leptin concentrations, and to clarify the relationship between paraoxonase activity and a set of cardiovascular risk factors in malnourished, normal weight and obese HD patients; 114 HD patients with end-stage renal failure were enrolled. Results: Leptin levels were significantly higher and PON1 paraoxonase activities were significantly lower in obese patients compared to the other groups. Plasma adiponectin concentration was significantly lower in obese subjects compared to malnourished patients. Paraoxonase activity was negatively correlated with CRP level in HD and malnourished patients. Furthermore, we found significant inverse correlation between paraoxonase activity and BMI in the whole patient group. In multiple regression analysis, PON1 lactonase activity, CRP level and leptin concentration proved to be independent predictors of paraoxonase activity. Conclusion: Despite the previous findings of reverse epidemiology for the mortality rate of HD patients, further studies are needed to clarify the effects of nutritional state on atherosclerosis in obese and malnourished patients with end-stage renal failure.

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          Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure.

          Gregg C. Fonarow, TAMARA HORWICH, Gladys Block … (2004)
          Traditional risk factors of a poor clinical outcome and mortality in the general population, including body mass index (BMI), serum cholesterol, and blood pressure (BP), are also found to relate to outcome in patients with chronic heart failure (CHF), but in an opposite direction. Obesity, hypercholesterolemia, and high values of BP have been demonstrated to be associated with greater survival among CHF patients. These findings are in contrast to the well-known associations of over-nutrition, hypercholesterolemia, and hypertension with a poor outcome in the general population. The association between traditional cardiovascular risk factors and an adverse clinical outcome in CHF patients is referred to as "reverse epidemiology." The mechanisms for this inverse association in CHF is not clear. There are other populations with a similar risk factor reversal phenomenon, including patients with end-stage renal disease receiving dialysis, those with advanced malignancies, and individuals with advanced age. Several possible causes are hypothesized: the time discrepancy of the competing risk factors may play a role; the presence of the "malnutrition-inflammation complex syndrome" in CHF patients may explain the existence of reverse epidemiology; and a decreased level of lipoprotein molecules may distort their endotoxin-scavenging role, predisposing CHF patients with a low serum cholesterol level to inflammatory consequences of endotoxemia. It is possible that new goals for such traditional risk factors as BMI, serum cholesterol, and BP should be developed for CHF. Reverse epidemiology of conventional cardiovascular risk factors is observed in CHF and may have a bearing on the management of these patients; thus, it deserves further investigation.
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            Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance.

            P Sucharda, Josef V Silha, René Murphy … (2003)
            Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.
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              Modulation of paraoxonase (PON1) activity.

              Pietra L. Costa, Annabella Vitalone, B. Cole … (2005)
              Paraoxonase 1 (PON1) is a serum enzyme closely associated with high density lipoprotein (HDL). PON1 hydrolyzes several organophosphorus compounds used as insecticides, as well as nerve agents; it metabolizes toxic oxidized lipids associated with both low density lipoprotein (LDL) and HDL; and it can hydrolyze a number of lactone-containing pharmaceutical compounds, inactivating some, while activating others. Serum PON1 activity in a given population can vary by 40-fold. Though most of this variation can be explained by polymorphisms in the coding region (Q192R) and the 5' regulatory region (T-108C), modulation of PON1 by a variety of other factors should be taken into account, including other polymorphisms recently discovered but not yet characterized. This paper examines the major factors (environmental chemicals, drugs, smoking, alcohol, diet, age, disease conditions) that have been shown to modulate PON1 activity in either direction. As PON1 plays a protective role in organophosphate toxicity, and, because of its antioxidant capacity, in cardiovascular disease, a better understanding of how PON1 can be modulated by environmental factors has potential toxicological and clinical consequences.
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                Author and article information

                Journal
                Journal ID (publisher-id): KBR
                Journal ID (nlm-ta): Kidney Blood Press Res
                Journal ID (doi): 10.1159/issn.1420-4096
                Title: Kidney and Blood Pressure Research
                Publisher: S. Karger AG
                ISSN (Print): 1420-4096
                ISSN (Electronic): 1423-0143
                Publication date Subscription-year: 2012
                Publication date (Print): February 2013
                Publication date (Electronic): 12 December 2012
                Volume: 36
                Issue: 1
                Pages: 310-319
                Affiliations
                aFirst Department of Medicine, bInstitute of Surgery, University of Debrecen, Medical and Health Science Center, Debrecen
                Author notes
                *György Paragh, MD, DSc, First Department of Medicine, University of Debrecen, Medical and Health Science, Center, Nagyerdei krt. 98., H-4012 Debrecen (Hungary), Tel./Fax +36-52-442-101, E-Mail paragh@internal.med.unideb.hu
                Article
                Publisher ID: 343383 Other ID: Kidney Blood Press Res 2012;36:310-319
                DOI: 10.1159/000343383
                PubMed ID: 23235285
                SO-VID: ec8f4362-6fdc-4ccc-8c6c-cc029fac4867
                Copyright © © 2012 S. Karger AG, Basel
                License:

                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
                Date accepted : 12 November 2012
                Page count
                Pages: 10
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Paraoxonase,Nutritional state,Reverse epidemiology,C-reactive protein,Chronic kidney disease,Obesity,Hemodialysis
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Paraoxonase, Nutritional state, Reverse epidemiology, C-reactive protein, Chronic kidney disease, Obesity, Hemodialysis

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