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Elevated serum macrophage migration inhibitory factor (MIF) concentrations in chronic kidney disease (CKD) are associated with markers of oxidative stress and endothelial activation.
Full Abstract
Chronic kidney disease (CKD) carries an increased risk of cardiovascular disease (CVD). Macrophage migration inhibiting factor (MIF) is a proinflammatory cytokine implicated in the pathogenesis of sepsis, autoimmune disease, atherogenesis, and plaque instability, and is a known cardiac depressant. This post-hoc, cross-sectional study examined whether MIF serum concentrations are elevated in CKD patients. Our study included CKD 3-5 patients with moderate to severe renal dysfunction (n = 257) (mean age SD; 55 +/- 12 years) and 53 controls (60 +/- 12 years). Serum MIF concentrations, measured by enzyme-linked immunosorbent assay (ELISA), were studied in relation to glomerular filtration rate (GFR), presence of CVD, outcome and inflammatory and oxidative stress markers. MIF was significantly elevated in CKD patients compared with controls (CKD: median 676 [range 118-8275 pg/mL] controls: 433 [142-4707] pg/mL; P = 0.008). MIF was also associated with 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels (rho = 0.26; P = 0.001), a marker of oxidative stress, and ICAM-1 levels (rho = 0.14; P = 0.02), a marker of endothelial activation. However, the elevated MIF concentrations were neither correlated with glomerular filtration rate (GFR) nor inflammatory markers such as CRP, IL-6, and TNF. When combining MIF and IL-6 as a marker of inflammation, a significant increase in risk for CVD was found, but when analyzing all-cause mortality, this did not differ significantly with regard to mortality from inflamed patients with low MIF levels. The data suggest that increased serum MIF levels found in CKD is not caused primarily by poor renal function, but is associated with markers of oxidative stress and endothelial activation and may play a role in vascular disease associated with CKD.
Author information
Author/s: Bruchfeld, Annette (A); Carrero, Juan J (JJ); Qureshi, Abdul R (AR); Lindholm, Bengt (B); Barany, Peter (P); Heimburger, Olof (O); Hu, Maowen (M); Lin, Xinchun (X); Stenvinkel, Peter (P); Miller, Edmund J (EJ);
Affiliation: Division of Renal Medicine, Karolinska University Hospital, Department of Clinical Science, Interventions and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Annette.Bruchfeld(-atsign-)ki.se
Journal and publication information
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Journal: Molecular medicine (Cambridge, Mass.) (Mol Med), published in United States. (Language: eng)
Reference: -2009 Mar-Apr; vol 15 (issue 3-4) : pp 70-5
Dates: Created 2009/03/05; Completed 2009/04/17;
PMID: 19081768, status: MEDLINE (last retrieval date: 4/17/2009, IMS Date: )
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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