title: Inflammation modifies the association of osteoprotegerin with mortality in chronic kidney disease.
abstract: BACKGROUND
  The production and expression of osteoprotegerin (OPG), a bone regulating protein, is regulated by inflammatory cytokines.
  
  
  METHODS
  As clinical and experimental studies have implicated OPG in atherogenesis, we investigated serum OPG in relation to inflammation, endothelial dysfunction and oxidative stress markers in 265 chronic kidney disease (CKD) stage 5 patients. Cardiovascular disease (CVD), carotid plaques (n=69) and mortality (5 years) in relation to OPG were also analyzed, and the impact of inflammation on the association of OPG with mortality was evaluated.
  
  
  RESULTS
  OPG correlated positively with circulating surrogate markers of inflammatory, endothelial dysfunction and oxidative stress. Patients with clinical CVD or carotid plaques had higher concentrations of OPG than their respective counterparts. Increased OPG levels per se were related to higher cardiovascular and all-cause mortality even after adjustment for age, sex, C-reactive protein, diabetes mellitus and baseline CVD. Moreover, the presence of inflammation further and independently aggravated the hazard ratios (HR) for both cardiovascular (HR=2.8; 95% confidence interval [95% CI], 1.3-6.4; p=0.01) and all-cause (HR=2.5; 95% CI, 1.4-4.5; p<0.01) mortality.
  
  
  CONCLUSIONS
  Elevated OPG levels are associated with surrogate markers of inflammation, endothelial dysfunction, oxidative stress and CVD in CKD patients. Moreover, inflammation and OPG levels seem to have additive effects on survival.
authors.affiliation: Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsubara
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Juan Jesús
authors.initials: JJ
authors.lastname: Carrero
authors.forename: Jonas
authors.initials: J
authors.lastname: Axelsson
authors.forename: Olof
authors.initials: O
authors.lastname: Heimbürger
authors.forename: Peter
authors.initials: P
authors.lastname: Bárány
authors.forename: Anders
authors.initials: A
authors.lastname: Alvestrand
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Suliman
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000276:immunology / Q000401:mortality* / Q000503:physiopathology; D002423:Cause of Death; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000401:mortality* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood*; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000401:mortality* / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D018384:Oxidative Stress; D016016:Proportional Hazards Models; D011502:Protein-Energy Malnutrition / Q000276:immunology / Q000401:mortality; D017582:Renal Replacement Therapy; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human