Putative Role of Endothelial Lipase in Dialysis Patients with Hypoalbuminemia and Inflammation

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Abstract

A recent study suggests that inflammation and malnutrition are strongly associated with cardiovascular disease in dialysis patients. Endothelial lipase (EL) is a newly cloned physiological regulator of high-density lipoprotein cholesterol (HDL), which is associated with the progression of atherosclerosis. To clarify the role of EL in dialysis patients, we evaluated serum markers on the basis of the presence of hypoalbuminemia and inflammation. We divided the 97 study patients into two groups on the basis of serum albumin (Alb) and high-sensitive C-reactive protein (hsCRP) levels, and measured serum EL levels. Serum EL levels were significantly correlated with Alb, cholinesterase, log hsCRP, and log tumor necrosis factor-alpha. They were also assigned to one of three groups on the basis of hypoalbuminemia and inflammatory status. Serum EL levels were significantly higher and serum HDL levels were lower in patients with low serum Alb and/or high hsCRP levels than in those without these abnormalities. Furthermore, when patients were classified into two groups on the basis of the EL levels measured, cardiovascular disease events during the 2-year follow-up period were significantly greater in the group with higher EL levels. Our findings suggest that the link between EL, hypoalbuminemia and inflammation may play an important role in atherogenesis in dialysis patients. Copyright 2008 S. Karger AG, Basel.

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

P Stenvinkel, O Heimbürger, F Paultre … (1999)

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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Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome).

P Stenvinkel, O Heimbürger, B. Lindholm … (2000)

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Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Cathy Critchlow, Jon S Anthony, Ronald L. Pisoni … (2006)

Mortality risk among hemodialysis (HD) patients may be highest soon after initiation of HD. A period of elevated mortality risk was identified among US incident HD patients, and which patient characteristics predict death during this period and throughout the first year was examined using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS; 1996 through 2004). A retrospective cohort study design was used to identify mortality risk factors. All patient information was collected at enrollment. Life-table analyses and discrete logistic regression were used to identify a period of elevated mortality risk. Cox regression was used to estimate adjusted hazard ratios (HR) measuring associations between patient characteristics and mortality and to examine whether these associations changed during the first year of HD. Among 4802 incident patients, risk for death was elevated during the first 120 d compared with 121 to 365 d (27.5 versus 21.9 deaths per 100 person-years; P = 0.002). Cause-specific mortality rates were higher in the first 120 d than in the subsequent 121 to 365 d for nearly all causes, with the greatest difference being for cardiovascular-related deaths. In addition, 20% of all deaths in the first 120 d occurred subsequent to withdrawal from dialysis. Most covariates were found to have consistent effects during the first year of HD: Older age, catheter vascular access, albumin <3.5, phosphorus <3.5, cancer, and congestive heart failure all were associated with elevated mortality. Pre-ESRD nephrology care was associated with a significantly lower risk for death before 120 d (HR 0.65; 95% confidence interval 0.51 to 0.83) but not in the subsequent 121- to 365-d period (HR 1.03; 95% confidence interval 0.83 to 1.27). This care was related to approximately 50% lower rates of both cardiac deaths and withdrawal from dialysis during the first 120 d. Mortality risk was highest in the first 120 d after HD initiation. Inadequate predialysis nephrology care was strongly associated with mortality during this period, highlighting the potential benefits of contact with a nephrologist at least 1 mo before HD initiation.

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Journal

Journal ID (publisher-id): AJN

Journal ID (nlm-ta): Am J Nephrol

Journal ID (doi): 10.1159/issn.0250-8095

Title: American Journal of Nephrology

Publisher: S. Karger AG

ISSN (Print): 0250-8095

ISSN (Electronic): 1421-9670

Publication date Subscription-year: 2008

Publication date (Print): October 2008

Publication date (Electronic): 09 July 2008

Volume: 28

Issue: 6

Pages: 974-981

Affiliations

^aDivision of Nephrology and Kidney Center, ^bDivision of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, Kobe, and ^cDivision of Nephrology, Akebono Clinic, Kumamoto, Japan

Article

Publisher ID: 144025 Other ID: Am J Nephrol 2008;28:974–981

DOI: 10.1159/000144025

PubMed ID: 18612200

SO-VID: 329d7df8-216f-48a6-9994-37491dc2908b

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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 received : 05 April 2008

Date accepted : 19 May 2008

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Pages: 8

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Putative Role of Endothelial Lipase in Dialysis Patients with Hypoalbuminemia and Inflammation

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Abstract

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Karger: Nephrology

Most cited references 21

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

Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome).

Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

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