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Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease.
Nephrol Dial Transplant. 2012 Jan; 27(1):70-5.ND

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+Show Affiliations

St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital, University of New South Wales, Sydney, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21940482

Citation

Breit, Samuel N., et al. "Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) and Mortality in End-stage Renal Disease." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 27, no. 1, 2012, pp. 70-5.
Breit SN, Carrero JJ, Tsai VW, et al. Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease. Nephrol Dial Transplant. 2012;27(1):70-5.
Breit, S. N., Carrero, J. J., Tsai, V. W., Yagoutifam, N., Luo, W., Kuffner, T., Bauskin, A. R., Wu, L., Jiang, L., Barany, P., Heimburger, O., Murikami, M. A., Apple, F. S., Marquis, C. P., Macia, L., Lin, S., Sainsbury, A., Herzog, H., Law, M., ... Brown, D. A. (2012). Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 27(1), 70-5. https://doi.org/10.1093/ndt/gfr575
Breit SN, et al. Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) and Mortality in End-stage Renal Disease. Nephrol Dial Transplant. 2012;27(1):70-5. PubMed PMID: 21940482.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease. AU - Breit,Samuel N, AU - Carrero,Juan J, AU - Tsai,Vicky Wang-Wei, AU - Yagoutifam,Nasreen, AU - Luo,Wei, AU - Kuffner,Tamara, AU - Bauskin,Asne R, AU - Wu,Liyun, AU - Jiang,Lele, AU - Barany,Peter, AU - Heimburger,Olof, AU - Murikami,Mary-Ann, AU - Apple,Fred S, AU - Marquis,Christopher P, AU - Macia,Laurence, AU - Lin,Shu, AU - Sainsbury,Amanda, AU - Herzog,Herbert, AU - Law,Matthew, AU - Stenvinkel,Peter, AU - Brown,David A, Y1 - 2011/09/22/ PY - 2011/9/24/entrez PY - 2011/9/24/pubmed PY - 2012/5/30/medline SP - 70 EP - 5 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 27 IS - 1 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 = 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. SN - 1460-2385 UR - https://www.unboundmedicine.com/medline/citation/21940482/Macrophage_inhibitory_cytokine_1__MIC_1/GDF15__and_mortality_in_end_stage_renal_disease_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfr575 DB - PRIME DP - Unbound Medicine ER -