Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients

Bologa, Roxana; Levine, DM; Ts, Parker; Js, Cheigh; Serur, David; Kh, Stenzel; Al, Rubin

doi:10.1053/ajkd.1998.v32.pm9669431

Cited by 515 publications

(362 citation statements)

References 23 publications

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“…Although the principal biomarker of inflammation measured in our study (IL-6) was different from those measured in previous longitudinal studies (CRP, IL-1␤, and IL-1 receptor antagonist), the discrepancies between our results and theirs may also be caused by differences in population characteristics (note that we excluded patients with BMI less than 20 kg/m 2 and/or albumin levels less than 35 g/L), sample size, and observation time. Additionally, a decrease in the levels of most laboratory nutritional markers (such as albumin, cholesterol, or transferrin) was interpreted as a negative acutephase response to inflammatory stimuli in several of the above studies (26,37,39,42) and not necessarily as a decline in nutritional status.…”

Section: Discussionmentioning

confidence: 99%

“…The malignant form of PEW, essentially caused by chronic inflammation in the HD population, is associated with pronounced hypoalbuminemia, markedly increased resting energy expenditure, oxidative stress, and poor clinical outcome, and has been termed as "malnutrition type 2" by Stenvinkel et al (25). However, clinical data suggesting a significant role for IL-6 in mediating PEW in ESRD patients are available only from cross-sectional analyses (17,18,26,27) or based on similarity with the pathophysiology of PEW in cancer cachexia (15,25). Longitudinal studies designed to determine the impact of inflammation on nutritional parameters in a prevalent dialysis cohort are still lacking.…”

Section: Introductionmentioning

confidence: 99%

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IL-6 Levels, Nutritional Status, and Mortality in Prevalent Hemodialysis Patients

Beberashvili

Sinuani

Azar

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives The influence of serum IL-6 levels on nutritional status in chronic hemodialysis (HD) patients remains to be elucidated. The present report describes a prospective longitudinal study of IL-6 levels and nutritional parameters to determine whether high IL-6 levels are independently associated with nutritional status over time in a cohort of prevalent hemodialysis patients.Design, setting, participants, & measurements 85 clinically stable hemodialysis patients (37.6% women), with a mean age of 66.5 Ϯ 10.6 years, were studied after exclusion of patients with BMI Ͻ 20 kg/m 2 and/or serum albumin Ͻ35 g/L. IL-6, dietary energy and protein intake, and biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18, and 24 months following enrollment. Observation of this cohort was continued over 2 additional years.Results IL-6 levels increased with time in both unadjusted (linear estimate: 2.57 Ϯ 0.44 pg/ml per 2 yrs; P ϭ 0.001) and adjusted models (linear estimate: 2.35 Ϯ 0.57 pg/ml per 2 yrs; P ϭ 0.049). Significant reductions of daily energy intake, laboratory markers (albumin, transferrin, cholesterol, creatinine), and body composition (fat mass) with higher IL-6 levels were observed over the duration of the longitudinal observation period. However, none of the studied parameters were associated with changes in IL-6 levels over time (IL-6-by-time interactions were NS). Furthermore, cumulative incidences of survival were correlated with the baseline serum IL-6 levels (P ϭ 0.004 by log-rank test). Finally, for each pg/ml increase in IL-6 level, the hazard ratio for death from all causes was 1.06 (95% CI 1.01 to 1.10) after adjustment for demographic and clinical parameters. ConclusionsOur results suggest that higher serum IL-6 levels are associated with all-cause mortality without additional changes in clinical and laboratory markers of nutritional status in clinically stable HD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

IL-6 Levels, Nutritional Status, and Mortality in Prevalent Hemodialysis Patients

Beberashvili

Sinuani

Azar

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…Interestingly, LPD also resulted in a reduction of the elevated levels of two markers of low-grade inflammation (CRP and IL-6). Elevated IL-6 levels have been reported to be associated with reduced albumin concentration in end-stage renal disease [30]. Thus, it cannot be excluded that a low-grade inflammatory state may have lead to a reduced albumin hepatic response to macroalbuminuria, with consequent reduced plasma albumin levels.…”

Section: Discussionmentioning

confidence: 99%

Effects of dietary protein restriction on albumin and fibrinogen synthesis in macroalbuminuric type 2 diabetic patients

et al. 2007

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Aims/hypothesis Diabetic nephropathy is associated with hypoalbuminaemia and hyperfibrinogenaemia. A lowprotein diet has been recommended in patients with diabetic nephropathy, but its effects on albumin and fibrinogen synthesis are unknown. Methods We compared the effects of a normal (NPD; 1.38± 0.08 g kg −1 day −1 ) or low (LPD; 0.81±0.04 g kg −1 day −1 ) -protein diet on endogenous leucine flux (ELF), albumin and fibrinogen synthesis (L-[5,5,5,-2 H 3 ]leucine infusion), and markers of inflammation in nine type 2 diabetic patients with macroalbuminuria. Six healthy participants on NPD served as control participants. Results In comparison with healthy participants, type 2 diabetic patients on an NPD had similar ELF, reduced serum albumin (38±1.1 vs 42±0.8 g/l; p<0.05), similar fractional synthesis rates (FSR) and absolute synthesis rates (ASR) of albumin, and both increased plasma fibrinogen concentration [10.7±0.6 vs 7.2±0.5 μmol/l (3.64±0.22 vs 2.45±0.18 g/l); p<0.05] and fibrinogen ASR [11.03±1.17 vs 6.0±1.8 μmol 1.73 m −2 day −1 (3.7±0.4 vs 1.9±0.3 g 1.73 m −2 day −1 ); p< 0.01]. After LPD, type 2 diabetic patients had the following changes in comparison with NPD: reduced proteinuria (2.74±0.4 vs 4.51±0.8 g/day; p<0.05), ELF (1.93±0.08 vs 2.11±0.08 μmol kg −1 min −1 ; p<0.05) and total fibrinogen pool; increased serum albumin (42±1 vs 38±1 g/l; p<0.01) and albumin ASR (14.1±1 vs 9.9±1 g 1.73 m −2 day −1 ; p< 0.05); and reduced plasma IL-6 levels, which were correlated with albumin ASR (r=−0.749; p<0.05). Conclusions/interpretation LPD in type 2 diabetic patients with diabetic nephropathy reduces low-grade inflammatory state, proteinuria, albuminuria, whole-body proteolysis and ASR of fibrinogen, while increasing albumin FSR, ASR and serum concentration. ISRCTN ID no: CCT-NAPN-16911Keywords Absolute synthesis . Albumin . Diabetic nephropathy . Fibrinogen . Fractional synthesis . Leucine . Low-grade inflammation . Low-protein diet . Macroalbuminuria . Type 2 diabetes Abbreviations ASR absolute synthesis rate CRP C-reactive protein ELF endogenous leucine flux FSR fractional synthesis rate KIC α-ketoisocaproic acid LPD low-protein diet Diabetologia (2008) 51:21-28

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“…IL-6 is a cytokine with multiple and complex endocrine effects on lipid metabolism: administration of IL-6 to nonhuman primates 10 and cancer patients 11 resulted in a decrease of total cholesterol levels, whereas in healthy volunteers, it caused a significant increase in total cholesterol. 24 In patients with myocardial infarction, 25 after major surgery, 26,27 or on hemodialysis, 28 circulating IL-6 levels are correlated negatively with total cholesterol levels. Thus, the molecular and cellular mechanisms that elicit IL-6 effects on lipoprotein metabolism need further investigation.…”

Section: Schieffer Et Al Interleukin-6 In Experimental Atherosclerosimentioning

confidence: 99%

Impact of Interleukin-6 on Plaque Development and Morphology in Experimental Atherosclerosis

Schieffer

Selle²,

Hilfiker³

et al. 2004

Circulation

286

189

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Background— Vascular lipid accumulation and inflammation are hallmarks of atherosclerosis and perpetuate atherosclerotic plaque development. Mediators of inflammation, ie, interleukin (IL)-6, are elevated in patients with acute coronary syndromes and may contribute to the exacerbation of atherosclerosis. Methods and Results— To assess the role of IL-6 in atherosclerosis, ApoE −/− – IL-6 −/− double-knockout mice were generated, fed a normal chow diet, and housed for 53±4 weeks. Mortality and blood pressure were unaltered. However, serum cholesterol levels and subsequent atherosclerotic lesion formation (oil red O stain) were significantly increased in ApoE −/− – IL-6 −/− mice compared with ApoE −/− , wild-type (WT), and IL-6 −/− mice. Plaques of ApoE −/− – IL-6 −/− mice showed significantly reduced transcript and protein levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, collagen I and V, and lysyl oxidase (by reverse transcriptase-polymerase chain reaction and immunohistochemistry). Recruitment of macrophages and leukocytes (Mac3- and CD45-positive staining) into the atherosclerotic lesion was significantly reduced in ApoE −/− – IL-6 −/− mice. The transcript and serum protein (ELISA) levels of IL-10 were significantly reduced. Conclusions— Thus, a lifetime IL-6 deficiency enhances atherosclerotic plaque formation in ApoE K −/− – IL-6 −/− mice and leads to maladaptive vascular developmental processes. These observations are consistent with the notion that baseline levels of IL-6 are required to modulate lipid homeostasis, vascular remodeling, and plaque inflammation in atherosclerosis.

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Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients

Cited by 515 publications

References 23 publications

IL-6 Levels, Nutritional Status, and Mortality in Prevalent Hemodialysis Patients

IL-6 Levels, Nutritional Status, and Mortality in Prevalent Hemodialysis Patients

Effects of dietary protein restriction on albumin and fibrinogen synthesis in macroalbuminuric type 2 diabetic patients

Impact of Interleukin-6 on Plaque Development and Morphology in Experimental Atherosclerosis

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