Filtration of Macrophage Migration Inhibitory Factor (MIF) in Patients with End Stage Renal Disease Undergoing Hemodialysis

Abstract

BackgroundEnd stage renal disease (ESRD) patients are characterized by increased morbidity and mortality due to highest prevalence of cardiovascular disease. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that controls cellular signaling in human physiology, pathophysiology, and diseases. Increased MIF plasma levels promote vascular inflammation and development of atherosclerosis. We have shown that MIF is associated with vascular dysfunction in ESRD patients. Whether hemodialysis (HD) affects circulating MIF plasma levels is unknown. We here aimed to investigate whether HD influences the circulating MIF pool in ESRD patients.Methods and ResultsAn observational single-center study was conducted. MIF plasma levels in ESRD patients were assessed before, during, and after a HD session (n = 29). Healthy age-matched volunteers served as controls to compare correlations of MIF plasma levels with inflammatory plasma components (n = 20). MIF removed from the circulating blood pool could be detected in the dialysate and allowed for calculation of totally removed MIF (MIF content in dialysate 219±4 μg/HD-session). MIF plasma levels were markedly decreased 2 hour after initiation of HD (MIF plasma level pre-HD 84.8±6 ng/ml to intra-HD 61.2±5 ng/ml p<0.001) and were replenished already 20 min after termination of HD to basal levels (intra-HD 61.2±5 ng/ml to post-HD 79.8±5 ng/ml, p<0.001).ConclusionMIF is a dialyzable plasma component that is effectively filtrated during HD from the patient blood pool in large amounts. After removal of remarkable amounts of MIF during a single HD session, MIF plasma pool is early reconstituted after termination of HD from unknown sources.

Renal replacement therapy neutralizes elevated MIF levels in septic shock

“…In experimental sepsis models, MIF inhibition by MIF antibodies and MIF receptor antagonists was shown to protect from septic shock and to improve survival [ 9 , 33 , 34 ]. We recently showed that hemodialysis is an effective tool to neutralize circulating MIF by removal from the blood pool in patients with end-stage renal failure [ 18 ]. In the present study, we show first evidence of the effect of lowering MIF levels in patients undergoing CRRT in septic shock.…”

“…It is more likely to assume that MIF levels are lowered by CRRT since conduction of CRRT is the only obvious MIF-influencing difference between our groups. Furthermore, our group proofed effective removal of MIF by dialysis before [ 18 ]. In addition, the comparison of decrease of MIF levels with decrease of creatinine levels during CRRT showed a close correlation (Additional file 2 : Figure S2) hinting at a similar mechanism.…”

“…We recently showed that MIF is a plasma component that can be dialyzed effectively during hemodialysis in chronically ill patients suffering from end-stage renal failure [ 18 ]. Whether circulating MIF levels are increased in septic patients with AKI and whether CRRT removes circulating MIF is not known.…”

Myocardial Expression of Macrophage Migration Inhibitory Factor in Patients with Heart Failure

“…Macrophage migration inhibitory factor (MIF) is known as a pleiotropic inflammatory cytokine and has been recognized as a mediator of a number of inflammatory diseases including sepsis and atherosclerosis [ 8 , 9 , 10 , 11 , 12 , 13 ]. It has recently been described that MIF plays a role in NICM, since expression of MIF in myocardial biopsy samples predicted all-cause mortality in NICM patients and was described as a novel additional tool to predict adverse outcome in patients with NICM [ 14 ].…”

How Does Continuous Renal Replacement Therapy Affect Septic Acute Kidney Injury?

“…It has been proved that decreased MIF concentration in cancer can induce macrophage polarization from proinflammatory macrophages (predominantly CD11b + /Ly6C high cells) to pro-wound healing macrophages (CD11b + /Ly6C intermediate cells) [33]. The MIF level decreases obviously during CRRT or hemodialysis and can improve the prognosis [23, 34]; however, how it works is still unknown and the MIF plasma pool is reconstituted early after the termination of hemodialysis from unknown sources. Probably the same thing happens during CRRT of septic AKI patients.…”