title: Elevated serum interleukin-18 level is associated with all-cause mortality in stable hemodialysis patients independently of cardiac dysfunction.
abstract: BACKGROUND
  High circulating interleukin (IL)-18 level predicts a higher hospitalization rate among dialysis patients, possibly through cardiovascular mechanisms; however, whether higher IL-18 level is associated with mortality in dialysis patients is less clear. In addition, its impacts on left ventricular (LV) function are also unknown. We conducted a cohort study to examine the impacts of IL-18 level on LV function and prognosis among clinically stable hemodialysis patients.
  
  
  METHODS
  Clinically stable patients undergoing maintenance hemodialysis (≥ 3 months) were prospectively enrolled from December 2008 to January 2009, and were followed up for 31 months. The enrolled patients (41% male, 66.4 ± 10.9 years of age) received 2-dimensional echocardiography and myocardial deformation (strain) analysis, including LV peak systolic longitudinal strain (GLS) and circumferential strain (CS). Laboratory measurements were also performed. Cox regression analysis was used to investigate prognostic factors.
  
  
  RESULTS
  Seventy-five patients were stratified into 2 groups by the median value of IL-18 (654.2 pg/ml). Between these 2 groups, there was no significant difference in baseline characteristics including LV ejection fraction. The high IL-18 group had a worse LV systolic function as demonstrated by reduced GLS and CS. Seventeen patients (22.7%) died during the follow-up period. Multivariate Cox regression analysis showed that low serum albumin, the presence of hypertension, high serum IL-18, and less negative GLS (>-15%) were independently associated with all-cause mortality. No significant interaction between IL-18 and less negative GLS was noted in the final Cox model.
  
  
  CONCLUSIONS
  Hemodialysis patients with high IL-18 levels tend to have worse LV systolic function and higher mortality rate. However, elevated serum IL-18 level is predictive of poor prognosis among stable hemodialysis patients, independently of LV dysfunction. This suggests an additional value of IL-18 to echocardiographic study in predicting all-cause mortality, and IL-18 may be helpful in early risk stratification of hemodialysis patients.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yen-Wen
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan.
authors.forename: Chi-Ting
authors.initials: CT
authors.lastname: Su
authors.affiliation: Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Department of Statistics, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Ru
authors.initials: YR
authors.lastname: Su
authors.affiliation: Graduate Institute of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Saprina P H
authors.initials: SP
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Catholic Fu-An Hospital, Yun-Lin, Taiwan.
authors.forename: Chun-Shin
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Liang-Miin
authors.initials: LM
authors.lastname: Tsai
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Junne-Ming
authors.initials: JM
authors.lastname: Sung
mesh_terms: D000368:Aged; D005260:Female; D006760:Hospitalization; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood* / Q000401:mortality; D020382:Interleukin-18 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D006435:Renal Dialysis; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000401:mortality; D016277:Ventricular Function, Left
chemical_list: C000589760:IL18 protein, human; D020382:Interleukin-18