title: Elevated serum macrophage migration inhibitory factor (MIF) concentrations in chronic kidney disease (CKD) are associated with markers of oxidative stress and endothelial activation.
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.
authors.affiliation: Division of Renal Medicine, Karolinska University Hospital, Department of Clinical Science, Interventions and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Annette.Bruchfeld@ki.se
authors.forename: Annette
authors.initials: A
authors.lastname: Bruchfeld
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Carrero
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Peter
authors.initials: P
authors.lastname: Barany
authors.forename: Olof
authors.initials: O
authors.lastname: Heimburger
authors.forename: Maowen
authors.initials: M
authors.lastname: Hu
authors.forename: Xinchun
authors.initials: X
authors.lastname: Lin
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003430:Cross-Sectional Studies; D004727:Endothelium / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D008263:Macrophage Migration-Inhibitory Factors