Skip Navigation

European Journal of Heart Failure 2005 7(4):479-484; doi:10.1016/j.ejheart.2004.09.013
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Sharma, R.
Right arrow Articles by Anker, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharma, R.
Right arrow Articles by Anker, S. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2005 European Society of Cardiology

Whole blood endotoxin responsiveness in patients with chronic heart failure: the importance of serum lipoproteins

Rakesh Sharmaa,1, Stephan von Haehlinga,1, Mathias Rauchhausa,b,1, Aidan P. Bolgera,1, Sabine Genth-Zotza,c, Wolfram Doehnera,b, Brian Oliverd, Philip A. Poole-Wilsona, Volk Hans-Dietere, Andrew J.S. Coatsa, Ian M. Adcockd and Stefan D. Ankera,b,*

a Clinical Cardiology, NHLI, Imperial College School of Medicine Dovehouse Street, SW3 6LY, London, UK
b Division of Applied Cachexia Research, Department of Cardiology, Charité Medical School Berlin, Germany
c Department of Medicine II, Johannes Gutenberg-University Mainz, Germany
d Thoracic Medicine, NHLI, Imperial College School of Medicine London, UK
e Department of Clinical Immunology, Charité Campus Mitte, Berlin, Germany

* Corresponding:author. Department of Clinical Cardiology National Heart and Lung Institute Dovehouse Street, London, SW3 6LY, UK. Tel.: +44 020 7351 8203; Fax: +44 020 7351 8733. E-mail address: s.anker{at}imperial.ac.uk


   Abstract
Top
 Notes
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background: Endotoxin [lipopolysaccharide (LPS)] may be an important stimulus for cytokine release in patients with chronic heart failure (CHF). We sought to investigate the relationship between whole blood endotoxin responsiveness and serum lipoprotein concentrations. It is not known if low-dose LPS is sufficient to stimulate immune activation.

Methods and results: Whole blood from 32 CHF patients (mean age 66±2 years, NYHA class 2.7±0.2, five female) and 11 healthy control subjects (mean age 47±4 years, six female) was stimulated with LPS at nine different concentrations (0.001 to 10 ng/mL), and tumor necrosis factor (TNF-{alpha}) release was quantified. Reference standard endotoxin at concentrations of 0, 0.6, 1, and 3 EU/ml was added to whole blood from nine CHF patients (age 64{alpha}9.1 years, all NYHA class II, eight male) and incubated for 6 h, the TNF-{alpha} production being measured. Serum lipoproteins were quantified using standard techniques. In CHF patients, there was an inverse relationship between whole blood TNF-{alpha} release and serum cholesterol which was strongest at 0.6 ng/mL of LPS (r=–0.53, p=0.002). A similar although weaker relationship was found for serum HDL. No such correlation was found in healthy subjects or with serum LDL (all r2<0.1). Low concentrations of LPS induced a stepwise increase in TNF-± release from whole blood to concentrations well above those seen in CHF.

Conclusions: Serum lipoproteins may play an important role in regulating LPS bioactivity in CHF. Very low LPS activity, at levels seen in vivo in CHF, can induce significant TNF-{alpha} production ex vivo.

Key Words: Heart failure • Immune system • Lipids • Lipopolysaccharide

Received January 5, 2004; Revised August 12, 2004; Accepted September 20, 2004


   1. Introduction
Top
 Notes
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Chronic heart failure (CHF) is a state of immune activation, with inflammatory cytokines contributing to both the central and the peripheral manifestations of this syndrome [1]. Elevated levels of tumor necrosis factor (TNF-{alpha}) and interleukin-6 (IL-6) have been demonstrated in patients with CHF, which may play a crucial role in the pathogenesis of this condition. Endotoxin [lipopolysaccharide (LPS)], a potent stimulator of cytokine release, has been proposed as being responsible for the immune activation that is present in heart failure [2].

Prolonged or repeated exposure to endotoxin induces a shift in TNF-{alpha} responsiveness with reduced production of proinflammatory cytokines. This phenomenon is called endotoxin desensitization, and it appears that it is also present in patients with severe heart failure, as suggested by our studies published in this issue of the journal [3]. Mononuclear cell responsiveness, however, represents only one aspect of the immune response in CHF. Whole blood studies, on the other hand, also take into account physiological factors that are present in plasma. The generation of an inflammatory cytokine response to LPS in whole blood depends upon the complex interaction of specific proteins and receptors [4,5]. Investigations in animal models have shown that serum lipoproteins can protect against lethal endotoxaemia [6,7]. Furthermore, in vivo studies in humans have demonstrated that lipoproteins can inhibit the effects of LPS, not only by binding and neutralizing it, but also by reducing CD14 expression on monocytes [8]. This suggests that lipoproteins may be important regulators of LPS bioactivity, although the influence of lipoproteins on cytokine production in CHF is not known.

Previous work has shown that the range of in vivo LPS bioactivity in patients with CHF is between 0.6 and 1.0 EU/mL [9]. However, it is not known whether this low level of endotoxin activity is sufficient to induce an inflammatory cytokine response in ex vivo whole blood.


   2. Methods
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Study population
We assessed the TNF-{alpha} generation capacity of whole blood taken from 32 stable CHF patients (mean age 66±2 years, NYHA class 2.7±0.2, five female) and 11 healthy control subjects (mean age 47±4 years, six female, Table 1) in whom serum TNF-{alpha} and soluble TNF receptors 1 and 2 (sTNFR-1 and 2, respectively) were also measured. In CHF patients, plasma levels of soluble TNF-{alpha} receptors (particularly sTNFR-1) predict survival better than TNF itself [10]. Standard reference endotoxin was added to whole blood from nine CHF patients (age 64±9.1 years, all NYHA class II, eight male).


View this table:
[in this window]
[in a new window]

  		Table 1 Clinical characteristics of study subjects

 
All patients were recruited from the Royal Brompton Hospital heart failure clinic, with a diagnosis of CHF being based on symptoms, clinical signs, and documented left ventricular impairment (left ventricular ejection fraction <40%). Patients were on stable medication for at least 3 months. Medication consisted of diuretics (81%), angiotensin-converting enzyme inhibitors (72%), and beta-blockers (46%). Cardiac cachexia was diagnosed if there was nonintentional nonedematous weight loss >7.5% occurring over at least 6 months [11]. Patients were subdivided into mild (NYHA class II), moderate (NYHA class III), or severe (NYHA class IV with edematous decompensation and/or cardiac cachexia) heart failure. According to this classification, 14 patients with mild CHF (mean age 64±3 years), 7 patients with moderate CHF (mean age 66±2 years), and 11 patients with severe CHF (mean age 69±2 years) were enrolled in this study. Serum cortisol, cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) concentrations were measured using standard techniques.

The local ethics committee approved the study, and all subjects gave written informed consent. No subject had clinical signs of infection, rheumatoid arthritis, renal failure (creatinine for all patients <180 µmol/l), or cancer at the time of assessment.

2.2. Serum cytokine parameters
Citrated venous blood samples were taken in the morning following an overnight fast and after supine rest for at least 15 min. TNF-{alpha} levels were measured using standard enzyme-linked immunosorbent assay kits (ELISA, Quantikine HS, R&D Systems, Minneapolis, USA; sensitivity 0.18 pg/ml). As TNF-{alpha} levels are known to be variable due to a short plasma half-life time, we also measured the more stable soluble TNF receptors 1 and 2 (sTNFR-1 and 2, Quantikine HS, R&D Systems; sensitivity 3 and 1 pg/ml, respectively).

2.3. Cell stimulation assays
Escherichia-coli (serotype 0111:B4)-derived LPS was diluted in Hanks' balanced salt solution (Sigma-Aldrich, Irvine, UK) and used to stimulate whole blood samples at 10 different final concentrations (0, 0.001 to 10 ng/mL). Addition of Hanks' balanced salt solution alone served as a control. Incubation was performed in a humidified atmosphere (37 °C, 5% CO2) in 1-mL aliquots for 24 h. Supernatants were collected and stored at –80 °C until analysis for TNF-{alpha} content (ELISA, R&D Systems). Detection limit for TNF-{alpha} was 16 pg/mL. All samples were analysed in duplicate and thawed only once for immediate analysis. For technical reasons, one patient's results could not be analysed for two doses of LPS (i.e., 0.3 and 0.6 ng/mL).

2.4. Additional studies using standard reference endotoxin
Stimulation of whole blood with low dose LPS: Standard reference endotoxin (EC6, BioWhittaker, UK) was added to whole blood samples from 9 CHF patients (age 64±9.1 years, all NYHA class II, 8 male) at concentrations of 0.0, 0.6, 1 and 3 EU/mL. Samples were incubated for 6 hours in a humidified atmosphere as described above, because pilot experiments indicated that TNF-{alpha} production was highest at this point in time when standard reference endotoxin was used (data not shown). TNF-{alpha} was quantified in plasma supernatants (high sensitivity chemiluminescent ELISA, 0.7–7000 pg/mL, Quantiglo, R&D systems, Minneapolis, USA).

2.5. Statistics
Results are reported as mean±S.E.M. Unpaired Student's t test, ANOVA with Fisher's post hoc test, ANOVA for repeated measures, MANOVA, and simple regression analysis were used as appropriate (StatView 4.5, Abacus Concepts, Berkeley, USA). The results for TNF-{alpha} were square-root-transformed to achieve normal distribution. A p value <0.05 was considered significant.


   3. Results
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Serum cytokine parameters
Patients with CHF had higher levels of TNF-{alpha} than the control subjects (4.5±0.5 vs. 2.6±0.4 pg/mL, p=0.04, Table 1). There was a significant relationship between the clinical severity of CHF and serum TNF-{alpha}, sTNFR-1, and sTNFR-2 concentrations, with the highest levels being found in patients with severe disease (mean TNF-{alpha}: 5.9 pg/mL; sTNFR-1: 2146 pg/mL; sTNFR-2: 4737 pg/mL; p<0.03, ANOVA).

3.2. Whole blood stimulation
There was no significant difference in TNF-{alpha} release from LPS-stimulated whole blood between controls and all patients (ANOVA for repeated measures: p>0.2, Fig. 1) or patients subdivided according to CHF severity (p>0.2, data not shown). When analysing the LPS concentrations of 0.1 to 1 ng/mL in isolation, there was a trend for higher TNF-{alpha} release in CHF patients as compared to controls (p=0.16).


Figure 1
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 TNF release from LPS-stimulated whole blood in CHF patients (n=32) and healthy controls (n=11).

 
Control subjects had significantly lower serum cortisol levels as compared to the CHF patients (288 vs. 478 nmol/L, p=0.0014). For both the control subjects and CHF patients, there was no significant relationship present between serum cortisol levels and whole blood LPS responsiveness (all r<0.3, p>0.1). Mean serum cholesterol levels were lower in CHF patients (4.6±0.2 mmol/L) than control subjects (5.4±0.3 mmol/L, p<0.05). However, there was no significant difference in serum HDL or LDL levels between CHF patients and controls (both p>0.2).

In CHF patients, there was an inverse relationship between whole blood TNF-{alpha} release and serum cholesterol (Fig. 2), which was strongest at 0.6 ng/mL of LPS (r=–0.53, p=0.002, Fig. 3). A similar although weaker relationship was found for serum HDL (Fig. 2). No such correlation was found in healthy subjects or with serum LDL (all r2<0.1).


Figure 2
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 The strength of the correlation between TNF release from LPS-stimulated whole blood in CHF patients and both serum cholesterol and serum HDL levels as represented by the r-squared value. *p<0.05; **p<0.01; (*)p=0.06.

 


Figure 3
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 The correlation between TNF release from LPS-stimulated whole blood and serum cholesterol in 31 patients with CHF at 0.6 ng/mL of LPS.

 
TNF-{alpha} production by whole blood in response to LPS was independent of age and the type of medication patients were taking.


   4. Discussion
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
This study shows that there is a significant inverse relationship between whole blood LPS responsiveness and serum cholesterol levels in CHF patients at a particular level of LPS stimulation. Very low LPS activity (at levels seen in vivo in patients with CHF) can induce significant TNF-{alpha} production ex vivo. This underscores the importance of circulating LPS as a trigger of cytokine production in vivo.

Cellular responsiveness to stimuli (like LPS) can be assessed ex vivo using different methodologies. Studying whole blood is completely different from studying isolated mononuclear cells. Studying mononuclear cells in isolation provides information about their status per se. It does not provide information about how these cells function in the human body being exposed to many competing influences. The limitation of studying isolated mononuclear cells is that this does not take into account physiological factors present in whole blood, which may play a crucial role in the inflammatory response. Several factors interfere with LPS action [12,13], and it is likely that these factors are able to induce or mitigate proinflammatory cytokine production. Therefore, it is important to use ex vivo models which are likely to mimic the in vivo setting. The interaction between serum cholesterol and whole blood LPS responsiveness has not been previously studied in heart failure.

The observed inverse correlation between TNF-{alpha} release from whole blood and serum cholesterol concentration in heart failure patients in the present study suggests that cholesterol (and possibly the totality of lipoproteins) may be able to inhibit the inflammatory response to endotoxin and therefore have a beneficial role in CHF. Lipoproteins have been proposed as having beneficial effects in patients with CHF by binding to and detoxifying endotoxin [14]. As the correlation between TNF-{alpha} release and serum cholesterol was significant only for a particular range of LPS concentrations (i.e., 0.3 to 1 ng/mL), there is an implication that there is a specific stoichiometric relationship between the binding of LPS and cholesterol molecules. The lack of this relationship in the control group is unclear. It may be that the complex interactions between LPS and cholesterol depend on other humoral factors which are augmented in heart failure. For example, there is evidence to suggest that circulating proteins, (such as sCD14 and LPS-binding protein) as well as other cytokines (e.g., interleukin-10), may regulate LPS–cell interactions and LPS bioactivity in CHF [4,12].

Additional evidence for the antiinflammatory actions of cholesterol comes from a study by Englund et al. which demonstrated that cholesterol can inhibit inflammatory cytokine production at both translational and transcriptional levels [15]. In their study, incubation of macrophages in vitro with cholesterol was able to decrease LPS-induced TNF-{alpha} release and also mRNA expression, inducing an effect similar to LPS desensitization.

It is known from large epidemiological studies that low cholesterol levels relate to an impaired prognosis [16,17]. In patients with CHF, low total cholesterol, low-density lipoprotein, high-density lipoprotein (HDL), and triglyceride levels are associated with a worse survival [18]. It has also been shown that the perioperative mortality rate of patients with severe CHF, supported by a left ventricular assist device, was higher in patients with low cholesterol levels [19]. In contrast, high lipoprotein levels and obesity have been found to be related to a favourable prognosis in CHF [20–22]. It may be proposed that high levels of cholesterol are beneficial in CHF due to the ability of serum lipoproteins to modulate inflammatory immune function.

It is evident from previous work that the range of LPS bioactivity in vivo in patients with decompensated CHF is between 0.6 and 1.0 EU/mL [9]. In the present study, we were able to demonstrate that even these low concentrations are able to stimulate significant TNF-{alpha} release (Fig. 4). This finding lends support to the hypothesis that LPS may be an important trigger for immune activation in patients with heart failure.


Figure 4
View larger version (11K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 4 The concentration of TNF in whole blood from 9 CHF patients stimulated with biologically relevant low doses of reference standard endotoxin and 6 hours incubation.

 
In conclusion, the present study has demonstrated that whole blood LPS responsiveness is inversely related to serum cholesterol levels, suggesting that they may play an important role in regulating LPS bioactivity in CHF. Very low LPS activity, at levels seen in vivo in patients with CHF, can induce significant TNF-{alpha} production ex vivo and therefore may be pathophysiologically relevant.


   Acknowledgements
 
RS was supported by the Robert Luff Foundation. APB, PPW, and the Department of Clinical Cardiology are supported by the British Heart Foundation. AJSC was supported by the Viscount Royston Trust Fund. SDA is supported by a Vandervell Fellowship and by a donation from Dr. Hubert Bailey. The Division of Applied Cachexia Research is supported by the Charité Medical School. SvH is supported by the German Heart Foundation, Frankfurt, Germany.


   Notes
Top
 Notes
Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
1 Rakesh Sharma, Stephan von Haehling, Mathias Rauchhaus and Aidan P. Bolger contributed equally to the work in this manuscript. Back


   References
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. von Haehling S., Jankowska E.A., Anker S.D. Tumour necrosis factor-alpha and the failing heart: pathophysiology and therapeutic implications. Basic Res. Cardiol. (2004) 99:18–28.[CrossRef][Web of Science][Medline]
  2. Anker S.D., Egerer K.R., Volk H.D., Kox W.J., Poole-Wilson P.A., Coats A.J. Elevated soluble CD14 receptors and altered cytokines in chronic heart failure. Am. J. Cardiol. (1997) 79:1426–1430.[CrossRef][Web of Science][Medline]
  3. Sharma R., Bolger A.P., von Haehling S., Doehner W., Adcock I.M., Barnes P.J., et al. Cellular endotoxin desensitization in patients with severe chronic heart failure. Eur. J. Heart Fail. (2005) 10.1016/j.ejheart.2004.09.014.
  4. Kitchens R.L., Thompson P.A., Viriyakosol S., O'Keefe G.E., Munford R.S. Plasma CD14 decreases monocyte responses to LPS by transferring cell-bound LPS to plasma lipoproteins. J. Clin. Invest. (2001) 108:485–493.[CrossRef][Web of Science][Medline]
  5. Medzhitov R., Janeway C. Jr. Innate immunity. N. Engl. J. Med. (2000) 343:338–344.[Free Full Text]
  6. Flegel W.A., Baumstark M.W., Weinstock C., Berg A., Northoff H. Prevention of endotoxin-induced monokine release by human low- and high-density lipoproteins and by apolipoprotein A-I. Infect. Immun. (1993) 61:5140–5146.[Abstract/Free Full Text]
  7. Harris H., Grunfeld C., Feingold K., Rapp J. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice. J. Clin. Invest. (1990) 86:696–702.[Web of Science][Medline]
  8. Pajkrt D., Doran J.E., Koster F., Lerch P.G., Arnet B., van der Poll T., et al. Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. J. Exp. Med. (1996) 184:1601–1608.[Abstract/Free Full Text]
  9. Niebauer J., Volk H.D., Kemp M., Dominguez M., Schumann R.R., Rauchhaus M., et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet (1999) 353:1838–1842.[CrossRef][Web of Science][Medline]
  10. Rauchhaus M., Clark A.L., Doehner W., Davos C., Bolger A., Sharma R., et al. The relationship between cholesterol and survival in patients with chronic heart failure. J. Am. Coll. Cardiol. (2003) 42:1933–1940.[Abstract/Free Full Text]
  11. Anker S.D., Ponikowski P., Varney S., Chua T.P., Clark A.L., Webb-Peploe K.M., et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet (1997) 349:1050–1053.[CrossRef][Web of Science][Medline]
  12. Bolger A.P., Sharma R., von Haehling S., Oliver B., Doehner W., Rauchhaus M., et al. Effect of interleukin-10 on the production of tumor necrosis factor-alpha by peripheral blood mononuclear cells from patients with chronic heart failure. Am. J. Cardiol. (2002) 90:384–389.[CrossRef][Web of Science][Medline]
  13. Parker T.S., Levine D.M., Chang J.C., Laxer J., Coffin C.C., Rubin A.L. Reconstituted high-density lipoprotein neutralizes gram-negative bacterial lipopolysaccharides in human whole blood. Infect. Immun. (1995) 63:253–258.[Abstract/Free Full Text]
  14. Rauchhaus M., Coats A., Anker S.D. The endotoxin-lipoprotein hypothesis. Lancet (2000) 356:930–933.[CrossRef][Web of Science][Medline]
  15. Englund M.C., Karlsson A.K., Wiklund O., Bondjers G., Ohlsson B.G. 25-hydroxycholesterol induces lipopolysaccharide-tolerance and decreases a lipopolysaccharide-induced TNF-alpha secretion in macrophages. Atherosclerosis (2001) 158:61–71.[CrossRef][Web of Science][Medline]
  16. Song Y.M., Sung J., Kim J.S. Which cholesterol level is related to the lowest mortality in a population with low mean cholesterol level: a 6.4-year follow-up study of 482,472 Korean men. Am. J. Epidemiol. (2000) 151:739–747.[Abstract/Free Full Text]
  17. Schatzkin A., Hoover R.N., Taylor P.R., Ziegler R.G., Carter C.L., Larson D.B., et al. Serum cholesterol and cancer in the NHANES I epidemiologic followup study. National Health and Nutrition Examination Survey. Lancet (1987) 2:298–301.[Web of Science][Medline]
  18. Vredevoe D.L., Woo M.A., Doering L.V., Brecht M.L., Hamilton M.A., Fonarow G.C. Skin test anergy in advanced heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy. Am. J. Cardiol. (1998) 82:323–328.[CrossRef][Web of Science][Medline]
  19. Richartz B.M., Radovancevic B., Frazier O.H., Vaughn W.K., Taegtmeyer H. Low serum cholesterol levels predict high perioperative mortality in patients supported by a left-ventricular assist system. Cardiology (1998) 89:184–188.[CrossRef][Web of Science][Medline]
  20. Horwich T.B., Fonarow G.C., Hamilton M.A., MacLellan W.R., Woo M.A., Tillisch J.H. The relationship between obesity and mortality in patients with heart failure. J. Am. Coll. Cardiol. (2001) 38:789–795.[Abstract/Free Full Text]
  21. Davos C.H., Doehner W., Rauchhaus M., Cicoira M., Francis D.P., Coats A.J., et al. Body mass and survival in patients with chronic heart failure without cachexia: the importance of obesity. J. Card. Fail. (2003) 9:29–35.[CrossRef][Web of Science][Medline]
  22. Rauchhaus M., Clark A.L., Doehner W., Davos C., Bolger A., Sharma R., et al. The relationship between cholesterol and survival in patients with chronic heart failure. J. Am. Coll. Cardiol. (2003) 42:1933–1940.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
S. von Haehling, W. Doehner, and S. D Anker
Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure
Cardiovasc Res, January 15, 2007; 73(2): 298 - 309.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
C. P. Kovesdy, J. E. Anderson, and K. Kalantar-Zadeh
Inverse Association between Lipid Levels and Mortality in Men with Chronic Kidney Disease Who Are Not Yet on Dialysis: Effects of Case Mix and the Malnutrition-Inflammation-Cachexia Syndrome
J. Am. Soc. Nephrol., January 1, 2007; 18(1): 304 - 311.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
R. D. Kilpatrick, C. J. McAllister, C. P. Kovesdy, S. F. Derose, J. D. Kopple, and K. Kalantar-Zadeh
Association between Serum Lipids and Survival in Hemodialysis Patients and Impact of Race
J. Am. Soc. Nephrol., January 1, 2007; 18(1): 293 - 303.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Sharma, R.
Right arrow Articles by Anker, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharma, R.
Right arrow Articles by Anker, S. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?