title: The circulating soluble TRAIL is a negative marker for inflammation inversely associated with the mortality risk in chronic kidney disease patients.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and an inadequate inflammatory response which may account for the high morbidity and mortality observed in this population. In vitro and preclinical evidence suggests that the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) might be involved in both the atherosclerosis pathway and modulation of the inflammatory response. The aim of the present study was thus to (i) determine serum levels of soluble TRAIL (sTRAIL) in a cohort of CKD patients, (ii) assess the relationship between sTRAIL and other inflammatory biomarkers (C-reactive protein and albumin) and (iii) evaluate the association between serum sTRAIL levels and the mortality risk.
  
  
  METHODS
  One hundred and thirty patients (mean +/- SD age: 67 +/- 12; 62% males; 8% at CKD stage 2, 26% at stage 3, 27% at stage 4, 8% at stage 5 and 31% at stage 5D) were assayed for sTRAIL and the selected biochemical parameters and then prospectively monitored for mortality.
  
  
  RESULTS
  CKD stage 5D patients had significantly lower serum sTRAIL levels (median: 46 pg/ml) than patients at CKD stages 2 and 3 (median: 62 pg/ml) or stages 4 and 5 (median: 71 pg/ml). There was no correlation between serum sTRAIL and the estimated glomerular filtration rate (GFR) (r(2) = 0.017, P = 0.22) in pre-dialysis patients. In a multivariate regression analysis, the body mass index (beta = 1.48, P = 0.001) and the serum C-reactive protein (CRP) level (beta = -8.841, P < 0.0001) were independently associated with serum sTRAIL. During follow-up (mean: 772 +/- 286 days), 36 patients died (19 from cardiovascular events, 8 from infectious events and 9 from other causes). The lowest sTRAIL levels (first tertile) were associated with the worst all-cause survival (P = 0.010). Cox regression analyses (with non-cumulative models including age, albumin and CRP as covariates) confirmed the low serum sTRAIL level (first tertile) as an independent predictor of all-cause mortality.
  
  
  CONCLUSIONS
  Circulating sTRAIL is a negative marker for inflammation and is inversely associated with the mortality risk in CKD patients. Further studies are needed to better understand the role of sTRAIL as an inflammatory marker and to confirm its protective role in the CKD population.
authors.affiliation: INSERM ERI-12 (EA 4292), Amiens, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Liabeuf
authors.forename: Daniela V
authors.initials: DV
authors.lastname: Barreto
authors.forename: Fellype C
authors.initials: FC
authors.lastname: Barreto
authors.forename: Maud
authors.initials: M
authors.lastname: Chasseraud
authors.forename: Michel
authors.initials: M
authors.lastname: Brazier
authors.forename: Gabriel
authors.initials: G
authors.lastname: Choukroun
authors.forename: Saïd
authors.initials: S
authors.lastname: Kamel
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*
chemical_list: D015415:Biomarkers; D012709:Serum Albumin; D053221:TNF-Related Apoptosis-Inducing Ligand; D002097:C-Reactive Protein