Association of Soluble Endotoxin Receptor CD14 and Mortality Among Patients Undergoing Hemodialysis

Dominic S.C. Raj, Vallabh O. Shah, Mehdi Rambod, Csaba Kovesdy, Kamyar Kalantar-Zadeh

Research output: Contribution to journalArticle

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Abstract

Background: CD14 is a key molecule in innate immunity that mediates cell activation and signaling in response to endotoxin and other bacterial wall-derived components. CD14 protein exists in soluble (sCD14) and membrane-bound forms. The correlates of sCD14 in persons undergoing long-term hemodialysis (HD) therapy are not known. We hypothesized that increased sCD14 levels in HD patients are associated with proinflammatory cytokine activation and increased mortality. Study Design: Cohort study. Setting & Participants: 310 long-term HD patients who participated in the Nutritional and Inflammatory Evaluation in Dialysis (NIED) Study, a cohort derived from a pool of more than 3,000 HD outpatients during 5 years in 8 DaVita maintenance dialysis facilities in the South Bay Los Angeles, CA, area. Predictors: sCD14 levels in serum. Outcomes: 33-month mortality. Results: Mean sCD14 level was 7.24 ± 2.45 μg/mL. Tumor necrosis factor α level was the strongest correlate of sCD14 level (r = +0.24; P < 0.001), followed by interleukin 6 level (r = +0.18; P = 0.002), serum ferritin level (r = +0.21; P < 0.001), total iron-binding capacity (r = -0.19; P < 0.001), body mass index (r = -0.15; P = 0.008), vintage (r = +0.14; P = 0.01), low-density lipoprotein cholesterol level (r = +0.13; P = 0.03), and body fat (r = -0.11; P = 0.06). During the 33-month follow-up, 71 (23%) patients died. Multivariable Cox proportional analysis adjusted for case-mix and other nutritional and inflammatory confounders, including serum tumor necrosis factor α, C-reactive protein, and interleukin 6 levels, showed that compared with the lowest sCD14 tertile, sCD14 levels in the third tertile (>7.8 μg/mL) were associated with greater death risk (hazard ratio, 1.94; 95% confidence interval, 1.01 to 3.75; P = 0.04). Limitations: Survivor bias in combined incident/prevalent studies. Conclusions: Increased sCD14 level is related positively to markers of inflammation and negatively to nutritional status and is an independent predictor of mortality in long-term HD patients. Additional studies are needed to examine the usefulness of sCD14 level in risk stratification and the clinical decision-making process in HD patients.

Original languageEnglish (US)
Pages (from-to)1062-1071
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume54
Issue number6
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

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Renal Dialysis
Mortality
Dialysis
Cohort Studies
Los Angeles
Nutritional Status
Innate Immunity
Endotoxins
Survivors
endotoxin receptor
Outpatients
Tumor Necrosis Factor-alpha
Odds Ratio
Maintenance
Confidence Intervals
Cytokines
Inflammation
Membranes
Serum
Proteins

All Science Journal Classification (ASJC) codes

  • Nephrology

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Association of Soluble Endotoxin Receptor CD14 and Mortality Among Patients Undergoing Hemodialysis. / Raj, Dominic S.C.; Shah, Vallabh O.; Rambod, Mehdi; Kovesdy, Csaba; Kalantar-Zadeh, Kamyar.

In: American Journal of Kidney Diseases, Vol. 54, No. 6, 01.12.2009, p. 1062-1071.

Research output: Contribution to journalArticle

Raj, Dominic S.C. ; Shah, Vallabh O. ; Rambod, Mehdi ; Kovesdy, Csaba ; Kalantar-Zadeh, Kamyar. / Association of Soluble Endotoxin Receptor CD14 and Mortality Among Patients Undergoing Hemodialysis. In: American Journal of Kidney Diseases. 2009 ; Vol. 54, No. 6. pp. 1062-1071.
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abstract = "Background: CD14 is a key molecule in innate immunity that mediates cell activation and signaling in response to endotoxin and other bacterial wall-derived components. CD14 protein exists in soluble (sCD14) and membrane-bound forms. The correlates of sCD14 in persons undergoing long-term hemodialysis (HD) therapy are not known. We hypothesized that increased sCD14 levels in HD patients are associated with proinflammatory cytokine activation and increased mortality. Study Design: Cohort study. Setting & Participants: 310 long-term HD patients who participated in the Nutritional and Inflammatory Evaluation in Dialysis (NIED) Study, a cohort derived from a pool of more than 3,000 HD outpatients during 5 years in 8 DaVita maintenance dialysis facilities in the South Bay Los Angeles, CA, area. Predictors: sCD14 levels in serum. Outcomes: 33-month mortality. Results: Mean sCD14 level was 7.24 ± 2.45 μg/mL. Tumor necrosis factor α level was the strongest correlate of sCD14 level (r = +0.24; P < 0.001), followed by interleukin 6 level (r = +0.18; P = 0.002), serum ferritin level (r = +0.21; P < 0.001), total iron-binding capacity (r = -0.19; P < 0.001), body mass index (r = -0.15; P = 0.008), vintage (r = +0.14; P = 0.01), low-density lipoprotein cholesterol level (r = +0.13; P = 0.03), and body fat (r = -0.11; P = 0.06). During the 33-month follow-up, 71 (23{\%}) patients died. Multivariable Cox proportional analysis adjusted for case-mix and other nutritional and inflammatory confounders, including serum tumor necrosis factor α, C-reactive protein, and interleukin 6 levels, showed that compared with the lowest sCD14 tertile, sCD14 levels in the third tertile (>7.8 μg/mL) were associated with greater death risk (hazard ratio, 1.94; 95{\%} confidence interval, 1.01 to 3.75; P = 0.04). Limitations: Survivor bias in combined incident/prevalent studies. Conclusions: Increased sCD14 level is related positively to markers of inflammation and negatively to nutritional status and is an independent predictor of mortality in long-term HD patients. Additional studies are needed to examine the usefulness of sCD14 level in risk stratification and the clinical decision-making process in HD patients.",
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AU - Raj, Dominic S.C.

AU - Shah, Vallabh O.

AU - Rambod, Mehdi

AU - Kovesdy, Csaba

AU - Kalantar-Zadeh, Kamyar

PY - 2009/12/1

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N2 - Background: CD14 is a key molecule in innate immunity that mediates cell activation and signaling in response to endotoxin and other bacterial wall-derived components. CD14 protein exists in soluble (sCD14) and membrane-bound forms. The correlates of sCD14 in persons undergoing long-term hemodialysis (HD) therapy are not known. We hypothesized that increased sCD14 levels in HD patients are associated with proinflammatory cytokine activation and increased mortality. Study Design: Cohort study. Setting & Participants: 310 long-term HD patients who participated in the Nutritional and Inflammatory Evaluation in Dialysis (NIED) Study, a cohort derived from a pool of more than 3,000 HD outpatients during 5 years in 8 DaVita maintenance dialysis facilities in the South Bay Los Angeles, CA, area. Predictors: sCD14 levels in serum. Outcomes: 33-month mortality. Results: Mean sCD14 level was 7.24 ± 2.45 μg/mL. Tumor necrosis factor α level was the strongest correlate of sCD14 level (r = +0.24; P < 0.001), followed by interleukin 6 level (r = +0.18; P = 0.002), serum ferritin level (r = +0.21; P < 0.001), total iron-binding capacity (r = -0.19; P < 0.001), body mass index (r = -0.15; P = 0.008), vintage (r = +0.14; P = 0.01), low-density lipoprotein cholesterol level (r = +0.13; P = 0.03), and body fat (r = -0.11; P = 0.06). During the 33-month follow-up, 71 (23%) patients died. Multivariable Cox proportional analysis adjusted for case-mix and other nutritional and inflammatory confounders, including serum tumor necrosis factor α, C-reactive protein, and interleukin 6 levels, showed that compared with the lowest sCD14 tertile, sCD14 levels in the third tertile (>7.8 μg/mL) were associated with greater death risk (hazard ratio, 1.94; 95% confidence interval, 1.01 to 3.75; P = 0.04). Limitations: Survivor bias in combined incident/prevalent studies. Conclusions: Increased sCD14 level is related positively to markers of inflammation and negatively to nutritional status and is an independent predictor of mortality in long-term HD patients. Additional studies are needed to examine the usefulness of sCD14 level in risk stratification and the clinical decision-making process in HD patients.

AB - Background: CD14 is a key molecule in innate immunity that mediates cell activation and signaling in response to endotoxin and other bacterial wall-derived components. CD14 protein exists in soluble (sCD14) and membrane-bound forms. The correlates of sCD14 in persons undergoing long-term hemodialysis (HD) therapy are not known. We hypothesized that increased sCD14 levels in HD patients are associated with proinflammatory cytokine activation and increased mortality. Study Design: Cohort study. Setting & Participants: 310 long-term HD patients who participated in the Nutritional and Inflammatory Evaluation in Dialysis (NIED) Study, a cohort derived from a pool of more than 3,000 HD outpatients during 5 years in 8 DaVita maintenance dialysis facilities in the South Bay Los Angeles, CA, area. Predictors: sCD14 levels in serum. Outcomes: 33-month mortality. Results: Mean sCD14 level was 7.24 ± 2.45 μg/mL. Tumor necrosis factor α level was the strongest correlate of sCD14 level (r = +0.24; P < 0.001), followed by interleukin 6 level (r = +0.18; P = 0.002), serum ferritin level (r = +0.21; P < 0.001), total iron-binding capacity (r = -0.19; P < 0.001), body mass index (r = -0.15; P = 0.008), vintage (r = +0.14; P = 0.01), low-density lipoprotein cholesterol level (r = +0.13; P = 0.03), and body fat (r = -0.11; P = 0.06). During the 33-month follow-up, 71 (23%) patients died. Multivariable Cox proportional analysis adjusted for case-mix and other nutritional and inflammatory confounders, including serum tumor necrosis factor α, C-reactive protein, and interleukin 6 levels, showed that compared with the lowest sCD14 tertile, sCD14 levels in the third tertile (>7.8 μg/mL) were associated with greater death risk (hazard ratio, 1.94; 95% confidence interval, 1.01 to 3.75; P = 0.04). Limitations: Survivor bias in combined incident/prevalent studies. Conclusions: Increased sCD14 level is related positively to markers of inflammation and negatively to nutritional status and is an independent predictor of mortality in long-term HD patients. Additional studies are needed to examine the usefulness of sCD14 level in risk stratification and the clinical decision-making process in HD patients.

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