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.

Macrophage migration inhibitory factor (MIF): A promising biomarker

“…The association between MIF and autoimmune kidney disease was further investigated by Bruchfeld et al, who studied 257 patients with chronic kidney disease different etiologies. They suggested that high MIF levels in these patients are closely linked to endothelial activation and that MIF might play a role in the vascular disease associated with chronic kidney disease [39]. …”

Macrophage migration inhibitory factor as a potential predictor for requirement of renal replacement therapy after orthotopic liver transplantation

“…The proinflammatory cytokine macrophage migration inhibitory factor (MIF) is associated with inflammatory nephritis, kidney transplant rejection, and chronic kidney dysfunction . Recently, Payen et al reported that MIF is increased in septic patients who developed AKI within 48 hours after intensive care unit admission.…”

“…16 The proinflammatory cytokine macrophage migration inhibitory factor (MIF) is associated with inflammatory nephritis, 17,18 kidney transplant rejection, 19 and chronic kidney dysfunction. 20 Recently, Payen et al 21 reported that MIF is increased in septic patients who developed AKI within 48 hours after intensive care unit admission. Elevated concentrations of MIF induce leukocyte chemotaxis and tissue infiltration by leukocytes, 22,23 and this is followed by histopathological organ damage to the lungs 24 and kidneys, 25 among others.…”

Vascular Endothelial Growth Factor-A, Matrix Metalloproteinase-1, and Macrophage Migration Inhibition Factor Changes in the Porcine Remnant Kidney Model: Evaluation by Magnetic Resonance Imaging

“…Macrophage migration inhibition factor is a proinflammatory cytokine which is involved in atherosclerosis and chronic kidney disease (8, 9). Until recently, there have not been many studies describing the role of MIF in kidney disease.…”

“…Until recently, there have not been many studies describing the role of MIF in kidney disease. A recent study showed that it was increased in the serum of patients with chronic kidney disease (9). In addition, it has been shown to be involved in kidney disease mediated by immunologic injury (8).…”