title: Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease.
abstract: BACKGROUND
  Elevated macrophage inhibitory cytokine-1 (MIC-1/GDF15) levels in serum mediate anorexia and weight loss in some cancer patients and similarly elevated levels occur in chronic kidney disease (CKD). Serum MIC-1/GDF15 is also elevated in chronic inflammatory diseases and predicts atherosclerotic events independently of traditional risk factors. The relationship between chronic inflammation, decreasing body mass index (BMI) and increased mortality in CKD is not well understood and is being actively investigated. MIC-1/GDF15 may link these features of CKD.
  
  
  METHODS
  Cohorts of incident dialysis patients from Sweden (n = 98) and prevalent hemodialysis patients from the USA (n = 381) had serum MIC-1/GDF15, C-reactive protein (CRP) levels and BMI measured at study entry. Additional surrogate markers of nutritional adequacy, body composition and inflammation were assessed in Swedish patients. Patients were followed for all-cause mortality.
  
  
  RESULTS
  In the Swedish cohort, serum MIC-1/GDF15 was associated with decreasing BMI, measures of nutrition and markers of oxidative stress and inflammation. Additionally, high serum MIC-1/GDF15 levels identified patients with evidence of protein-energy wasting who died in the first 3 years of dialysis. The ability of serum MIC-1/GDF15 to predict mortality in the first 3 years of dialysis was confirmed in the USA cohort. In both cohorts, serum MIC-1/GDF15 level was an independent marker of mortality when adjusted for age, CRP, BMI, history of diabetes mellitus and/or cardiovascular disease and glomerular filtration rate or length of time on dialysis at study entry.
  
  
  CONCLUSIONS
  MIC-1/GDF15 is a novel independent serum marker of mortality in CKD capable of significantly improving the mortality prediction of other established markers. MIC-1/GDF15 may mediate protein-energy wasting in CKD and represent a novel therapeutic target for this fatal complication.
authors.affiliation: St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Carrero
authors.forename: Vicky Wang-Wei
authors.initials: VW
authors.lastname: Tsai
authors.forename: Nasreen
authors.initials: N
authors.lastname: Yagoutifam
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Tamara
authors.initials: T
authors.lastname: Kuffner
authors.forename: Asne R
authors.initials: AR
authors.lastname: Bauskin
authors.forename: Liyun
authors.initials: L
authors.lastname: Wu
authors.forename: Lele
authors.initials: L
authors.lastname: Jiang
authors.forename: Peter
authors.initials: P
authors.lastname: Barany
authors.forename: Olof
authors.initials: O
authors.lastname: Heimburger
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Murikami
authors.forename: Fred S
authors.initials: FS
authors.lastname: Apple
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Marquis
authors.forename: Laurence
authors.initials: L
authors.lastname: Macia
authors.forename: Shu
authors.initials: S
authors.lastname: Lin
authors.forename: Amanda
authors.initials: A
authors.lastname: Sainsbury
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000401:mortality*; D012307:Risk Factors; D015996:Survival Rate; D013548:Sweden; D014481:United States
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D002097:C-Reactive Protein