TY - JOUR
T1 - Macrophage inhibitory cytokine-1(MIC-1/GDF15) and mortality in end-stage renal disease
AU - Breit, Samuel
AU - Carrero, Juan
AU - Tsai, Vicky
AU - Yagoutifam, Nasreen
AU - Luo, Wei
AU - Kuffner, Tamara
AU - Bauskin, A
AU - Wu, Liyun
AU - Jiang, Lele
AU - Barany, Peter
AU - Heimburger, Olof
AU - Murikami, Mary-Ann
AU - Apple, Fred
AU - Marquis, Christopher
AU - Macia, Laurence
AU - Lin, Shu
AU - Sainsbury, Amanda
AU - Herzog, Herbert
AU - Law, Matthew
AU - Stenvinkel, Peter
AU - Brown, David
PY - 2012
Y1 - 2012
N2 - 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 A? 98) and prevalent hemodialysis patients from the USA (n A? 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.
AB - 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 A? 98) and prevalent hemodialysis patients from the USA (n A? 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.
UR - http://ndt.oxfordjournals.org/content/early/2011/09/22/ndt.gfr575.full.pdf+html
U2 - 10.1093/ndt/gfr575
DO - 10.1093/ndt/gfr575
M3 - Article
VL - 27
SP - 70
EP - 75
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
SN - 0931-0509
IS - 1
ER -