title: Elevated Circulating Interleukin 33 Levels in Stable Renal Transplant Recipients at High Risk for Cardiovascular Events.
abstract: BACKGROUND
  The Major Adverse Cardiovascular Events calculator (CRCRTR-MACE) estimates the burden of cardiovascular risk in renal transplant recipients (RTR). Our recent study of 95 RTR reported the 7-year median risk of cardiovascular events (CVE) to be 9.97%, ranging from 1.93 to 84.27%. Nearly a third (28.4%) of the cohort was above 20% risk for a CVE. Since interleukins (ILs) as part of the inflammatory response may play a role in the pathogenesis of cardiovascular disease (CVD), we extended this study to identify which ILs are associated with high cardiovascular risk in this population.
  
  
  METHODS
  Twenty-two ILs were measured by multiplexed fluorescent bead-based immunoassay in 95 RTR and 56 normal controls. Stepwise analysis after multivariate determination of significant demographic and inflammatory variables was performed between the high and low-CVD risk groups (which were arbitrarily set at scores <10% and ≥20%, respectively). Normalized data was presented as mean ± SD and non-normalized data as median (minimum-maximum). Significance was measured at <0.05.
  
  
  RESULTS
  27.5% of the low-risk and 31.3% of the high-risk groups had mean IL levels above the 95 percentile of the normal control levels. In the non-parametric analysis IL-6, 9, 16, 17 and 33 were significantly higher in the high-risk group compared to the control. Univariate analysis (UVA) of the high-risk group identified IL-33 as the only IL that remained significantly higher than the control and low-risk groups (p = 0.000). The percentage of patients with IL-33 levels above the 90 percentile of control value in the low and high-risk groups were 15.6% and 52.0%, respectively (p<0.002). UVA of factors significant to high IL-33 levels included estimated glomerular filtration rate (eGFR), while diabetes mellitus, serum phosphorus, microalbuminuria and age also remained significant in the multivariate analysis.
  
  
  CONCLUSIONS
  Circulating IL-33 level is positively associated with high CRCRTR-MACE score. Diminished eGFR, age, diabetes, serum phosphorus and microalbuminurea demonstrate significant relationship with elevated IL-33 levels, supporting the possible pathognomonic role of IL-33 in the cardiovascular burden in RTR.
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatchewan, Canada.
authors.forename: Holly
authors.initials: H
authors.lastname: Mansell
authors.affiliation: St. Paul's Hospital, Saskatchewan Renal Transplant Program, Saskatoon, SK, Canada.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Soliman
authors.affiliation: St. Paul's Hospital, Saskatchewan Renal Transplant Program, Saskatoon, SK, Canada.
authors.forename: Hamdi
authors.initials: H
authors.lastname: Elmoselhi
authors.affiliation: St. Paul's Hospital, Saskatchewan Renal Transplant Program, Saskatoon, SK, Canada.|Department of Medicine, University of Saskatchewan, University of Saskatchewan, Saskatchewan, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Shoker
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology*; D005260:Female; D006801:Humans; D000067596:Interleukin-33 / Q000097:blood*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D000067596:Interleukin-33