Soluble CD14 levels, interleukin 6, and mortality among prevalent hemodialysis patients.
BACKGROUND
CD14 is a pattern-recognition receptor that has a central immunomodulatory role in proinflammatory signaling in response to a variety of ligands, including endotoxin. CD14 protein is present in 2 forms: soluble (sCD14) and membrane bound. Here, we studied the implications of increased sCD14 levels in hemodialysis patients. We hypothesized that sCD14 level increase may link to cytokine activation and protein-energy wasting, predisposing to increased mortality risk.


METHODS
Prospective observational study of prevalent hemodialysis patients.


METHODS
211 prevalent hemodialysis patients, median age of 65 years, with 29 months of vintage dialysis time followed up for mortality for a median of 31 months.


METHODS
Tertiles of baseline circulating sCD14 levels corresponding to less than 2.84, 2.85 to 3.62, and greater than 3.63 microg/mL.


RESULTS
The major outcome of interest was all-cause mortality.


METHODS
sCD14 and endotoxin, together with other markers of inflammation and protein-energy wasting.


RESULTS
Median sCD14 level was 3.2 microg/mL (25th to 75th percentile, 2.7 to 3.9). sCD14 level correlated positively with C-reactive protein, interleukin 6, endotoxin, and pentraxin 3 levels and negatively with serum albumin level, muscle mass, and handgrip strength. Patients with increased sCD14 levels had lower body mass index and increased prevalence of muscle atrophy. Patients within the highest sCD14 tertile had a crude morality hazard ratio of 1.94 (95% confidence interval, 1.13 to 3.32) that persisted after adjustment for multiple confounders (hazard ratio, 3.11; 95% confidence interval, 1.49 to 6.46). In patients with persistent inflammation, the presence of a concurrent sCD14 level increase gradually increased mortality risk, but this effect was less than multiplicative and failed to show a statistical interaction.


CONCLUSIONS
Those inherent to an observational study.


CONCLUSIONS
sCD14 level is associated with inflammation and protein-energy wasting in hemodialysis patients. It is a strong and independent predictor of mortality that warrants further assessment in the clinical setting regarding its usefulness as a complementary prognosticator to other general inflammatory markers.
Raj
Dominic S C
DS
Division of Renal Diseases and Hypertension, George Washington University, Washington, DC, USA.
Carrero
Juan J
JJ
Shah
Vallabh O
VO
Qureshi
Abdul R
AR
Bárány
Peter
P
Heimbürger
Olof
O
Lindholm
Bengt
B
Ferguson
Jennet
J
Moseley
Pope L
PL
Stenvinkel
Peter
P
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D004731:Endotoxins / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011502:Protein-Energy Malnutrition / Q000097:blood; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D000683:Serum Amyloid P-Component / Q000378:metabolism; D015996:Survival Rate; D013548:Sweden; D000099153:Pentraxins
D015415:Biomarkers; D002097:C-Reactive Protein; D004731:Endotoxins; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D000683:Serum Amyloid P-Component; D000099153:Pentraxins