Acute kidney injury (AKI) represents the most frequent complication after cardiac surgery. Macrophage migration inhibitory factor (MIF) is a stress-regulating cytokine that was shown to protect the heart from myocardial ischemia-reperfusion injury, but its role in the pathogenesis of AKI remains unknown. In an observational study, serum and urinary MIF was quantified in 60 patients scheduled for elective conventional cardiac surgery with the use of cardiopulmonary bypass. Cardiac surgery triggered an increase in MIF serum concentrations, and patients with high circulating MIF (>median) 12 hours after surgery had a significantly reduced risk of developing AKI (relative risk reduction, 72.7%; 95% confidence interval, 12 to 91.5%; P = 0.03). Experimental AKI was induced in wild-type and Mif-/- mice by 30 min of ischemia followed by 6 or 24 hours of reperfusion, or by rhabdomyolysis. Mif-deficient mice exhibited increased tubular cell injury, increased regulated cell death (necroptosis and ferroptosis), and enhanced oxidative stress. Therapeutic administration of recombinant MIF after ischemia-reperfusion in mice ameliorated AKI. In vitro treatment of tubular epithelial cells with recombinant MIF reduced cell death and oxidative stress as measured by glutathione and thiobarbituric acid reactive substances in the setting of hypoxia. Our data provide evidence of a renoprotective role of MIF in experimental ischemia-reperfusion injury by protecting renal tubular epithelial cells, consistent with our observation that high MIF in cardiac surgery patients is associated with a reduced incidence of AKI.

中文翻译：

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巨噬细胞迁移抑制因子在心脏手术后急性肾脏损伤中的保护作用。

急性肾损伤（AKI）代表心脏手术后最​​常见的并发症。巨噬细胞迁移抑制因子（MIF）是一种应力调节性细胞因子，可保护心脏免受心肌缺血-再灌注损伤，但其在AKI发病机理中的作用仍然未知。在一项观察性研究中，对60例计划进行择期常规心脏手术并使用心肺旁路手术的患者进行了血清和尿MIF定量分析。心脏手术触发了MIF血清浓度的增加，并且术后12小时高循环MIF（>中位数）的患者发生AKI的风险显着降低（相对风险降低72.7％；置信区间95％，12至91.5％； AKI降低）。 P = 0.03）。实验性AKI在野生型和Mif-/-小鼠中缺血30分钟，然后再灌注6或24小时，或通过横纹肌溶解诱导。Mif缺陷小鼠表现出肾小管细胞损伤增加，受调节的细胞死亡（坏死病和肥大病）增加以及氧化应激增加。小鼠缺血再灌注后重组MIF的治疗性给药可改善AKI。在缺氧情况下，通过谷胱甘肽和硫代巴比妥酸反应性物质测定，重组MIF体外治疗肾小管上皮细胞可降低细胞死亡和氧化应激。我们的数据通过保护肾小管上皮细胞提供了MIF在实验性缺血再灌注损伤中的肾脏保护作用的证据，