P19: Macrophage migration inhibitory factor is associated with endothelial dysfunction and arterial stiffness in patients with end-stage renal disease

Abstract

The morbidity and mortality of patients with End-Stage Renal Disease (ESRD) undergoing dialysis is significantly increased and cardiovascular disease accounts for a great majority of mortality in this population. The rapid progression of the atherosclerotic process is based on a constant low-grade inflammation with the involvement of endothelial dysfunction and vascular stiffness. Recently, the inflammatory pleiotropic cytokine macrophage migration inhibitory factor (MIF) has emerged as a major mediator of atherosclerosis in animals models and might be implicated in modulation of disease progression. In a cross sectional approach n = 38 patients with ESRD undergoing hemodialysis (mean age SD; 65 ± 13 years) and 13 age-matched controls (62 ± 5 years) were included. MIF levels measured using commercially available MIF-ELISA (R&D Systems) were higher in ESRD than in controls (84.7 ± 4 ng/ml vs 64.86 ± 3 ng/ml p = 0.02). Endothelial function was assessed by flow-mediated vasodilation (FMD) of the brachial artery and was lower in ESRD than in controls (3.5 ± 0.1% vs 6.3 ± 0.3%, p < 0.0001). High MIF levels in ESRD reflected impaired endothelial function (r = −0.38, p = 0.02). Parameters for arterial stiffness (Central blood pressure (cSBP), pulse pressure (PP) and central augmentation index (AIX)) were determined using an applanation tonometry device and a validated generalized transfer function (SphygmoCor, AtCor Medical) and MIF levels positively correlated with arterial stiffness indices in this cohort ([email protected] r = 0.42, p = 0.02; SBP: r = 0.33, p = 0.04; PP: r = 0.41, p = 0.009). Nitrite was measured by chemiluminescence and HPLC technique. MIF levels showed positive correlation with nitrite (r = 0.48, p = 0.002). Implication of MIF in atherosclerotic microvascular disease was reflected by highly significant correlation with high-sensitive Troponin I as a marker for end organ damage in ESRD (r = 0.42, p = 0.009). These data support the concept that MIF is strongly associated with the progression and severity of atherosclerotic disease, unmasking individuals with endothelial dysfunction, arterial stiffness and target organ damage in this high-risk population independent of other co-morbidities or traditional risk factors. MIF-targeted interventions might improve cardiovascular outcomes in this population. Nothing to disclose.