Association of soluble endotoxin receptor CD14 and mortality among patients undergoing hemodialysis.
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.


METHODS
Cohort study.


METHODS
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.


METHODS
sCD14 levels in serum.


RESULTS
33-month mortality.


RESULTS
Mean sCD14 level was 7.24 +/- 2.45 microg/mL. Tumor necrosis factor alpha 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 alpha, C-reactive protein, and interleukin 6 levels, showed that compared with the lowest sCD14 tertile, sCD14 levels in the third tertile (>7.8 microg/mL) were associated with greater death risk (hazard ratio, 1.94; 95% confidence interval, 1.01 to 3.75; P = 0.04).


CONCLUSIONS
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.
Raj
Dominic S C
DS
George Washington University School of Medicine, North Washington, DC, USA.
Shah
Vallabh O
VO
Rambod
Mehdi
M
Kovesdy
Csaba P
CP
Kalantar-Zadeh
Kamyar
K
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011502:Protein-Energy Malnutrition / Q000097:blood; D006435:Renal Dialysis; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014481:United States
D015415:Biomarkers; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
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