title: Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD.
abstract: OBJECTIVE
  CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD.
  
  
  METHODS
  We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m(2) for ≥3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006.
  
  
  RESULTS
  Plasma sCD14 was negatively associated with eGFR (ρ=-0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23-58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P<0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (ρ=-0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up.
  
  
  CONCLUSIONS
  Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis.
authors.affiliation: Department of Microbiology and Immunology, Division of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Ruben
authors.initials: R
authors.lastname: Poesen
authors.affiliation: Division of Renal Diseases and Hypertension, George Washington University, Washington, DC;
authors.forename: Ali
authors.initials: A
authors.lastname: Ramezani
authors.affiliation: Department of Microbiology and Immunology, Division of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Kathleen
authors.initials: K
authors.lastname: Claes
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, University of Leuven, Leuven, Belgium; and.
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.affiliation: Department of Microbiology and Immunology, Division of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Dirk
authors.initials: D
authors.lastname: Kuypers
authors.affiliation: George Washington University School of Medicine, Washington, DC.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Barrows
authors.affiliation: Division of Renal Diseases and Hypertension, George Washington University, Washington, DC;
authors.forename: Jagadeesan
authors.initials: J
authors.lastname: Muralidharan
authors.affiliation: Department of Microbiology and Immunology, Division of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Pieter
authors.initials: P
authors.lastname: Evenepoel
authors.affiliation: Department of Microbiology and Immunology, Division of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Björn
authors.initials: B
authors.lastname: Meijers
authors.affiliation: Division of Renal Diseases and Hypertension, George Washington University, Washington, DC; draj@mfa.gwu.edu.
authors.forename: Dominic S
authors.initials: DS
authors.lastname: Raj
mesh_terms: D000368:Aged; D001530:Belgium / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D018450:Disease Progression; D004731:Endotoxins / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D004731:Endotoxins; D018950:Lipopolysaccharide Receptors
keywords: CKD; endotoxin; inflammation; microbiome; soluble CD14