title: Increased basal nitric oxide amplifies the association of inflammation with all-cause and cardiovascular mortality in prevalent hemodialysis patients.
abstract: OBJECTIVE
  We tested the hypothesis that the basal nitric oxide (NO) levels in prevalent hemodialysis (HD) patients may associate with inflammatory cytokines, predisposing them to increased mortality risk.
  
  
  METHODS
  We performed a prospective cohort study of 76 prevalent HD patients (42 % women), with a mean age of 65.3 ± 11.8 years with a follow-up for almost 4 years (median--47 months, interquartile range -19-75 months). We measured basal NO, proinflammatory cytokines (TNF-α, IL-1, IL-6, and IL-10), dietary intake, biochemical parameters of nutrition, and body composition (anthropometry and bioimpedance analysis).
  
  
  RESULTS
  Among various cytokines studied, only IL-6 exhibited a statistically significant linear association (adjusted r = 0.31, p = 0.014) with NO. Statistical interaction analysis showed a departure from multiplicity of effects of high NO (above the median) with high IL-6 (above the median) levels: crude Cox hazard ratios for all-cause and cardiovascular mortality for the product termed IL-6 × NO were 2.73 with a 95 % CI of 1.38-5.40 (p = 0.004) and 5.03 with a 95 % CI of 1.76-14.40 (p = 0.003), respectively. Across the four IL-6 NO categories, the group with high IL-6 and high NO (above their median levels) exhibited worse outcomes in both, all-cause and cardiovascular mortality (multivariable adjusted hazard ratios were 3.06, 95 % CI of 1.24-7.54 and 3.95, 95 % CI of 1.02-15.32, respectively).
  
  
  CONCLUSIONS
  Chronic inflammation, as measured by higher serum IL-6 levels, in combination with high basal NO is associated with worse clinical outcomes in terms of all-cause and cardiovascular death in clinically stable prevalent HD patients.
authors.affiliation: Nephrology Division, Assaf Harofeh Medical Center, Affiliated with Sackler Faculty of Medicine, Tel Aviv University, Zerifin, Israel, iliab@asaf.health.gov.il.
authors.forename: Ilia
authors.initials: I
authors.lastname: Beberashvili
authors.forename: Inna
authors.initials: I
authors.lastname: Sinuani
authors.forename: Ada
authors.initials: A
authors.lastname: Azar
authors.forename: Hadas
authors.initials: H
authors.lastname: Kadoshi
authors.forename: Gregory
authors.initials: G
authors.lastname: Shapiro
authors.forename: Leonid
authors.initials: L
authors.lastname: Feldman
authors.forename: Judith
authors.initials: J
authors.lastname: Sandbank
authors.forename: Zhan
authors.initials: Z
authors.lastname: Averbukh
mesh_terms: D000368:Aged; D001823:Body Composition; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality*; D002423:Cause of Death; D015930:Diet Records; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000401:mortality*; D015850:Interleukin-6 / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D006435:Renal Dialysis; D012885:Skinfold Thickness
chemical_list: D015850:Interleukin-6; D009569:Nitric Oxide