Division of Clinical Pharmacology, Department of Anesthesiology, Vanderbilt University Medical School, Nashville, TN 37232, USA.
Free Radic Biol Med. 2011 Jun 1;50(11):1480-7. doi: 10.1016/j.freeradbiomed.2011.02.011. Epub 2011 Feb 18.
Acute kidney injury (AKI) frequently afflicts patients undergoing cardiopulmonary bypass and independently predicts death. Both hemoglobinemia and myoglobinemia are independent predictors of postoperative AKI. Release of free hemeproteins into the circulation is known to cause oxidative injury to the kidneys. This study tested the hypothesis that postoperative AKI is associated with both enhanced intraoperative hemeprotein release and increased lipid peroxidation assessed by measuring F₂-isoprostanes and isofurans. In a case-control study nested within an ongoing randomized trial of perioperative statin treatment and AKI, we compared levels of F₂-isoprostanes and isofurans with plasma levels of free hemoglobin and myoglobin in 10 cardiac surgery AKI patients to those of 10 risk-matched controls. Peak plasma free hemoglobin concentrations were significantly higher in AKI subjects (289.0 ± 37.8 versus 104.4 ± 36.5mg/dl, P = 0.01), whereas plasma myoglobin concentrations were similar between groups. The change in plasma F₂-isoprostane and isofuran levels (repeated-measures ANOVA, P = 0.02 and P = 0.001, respectively) as well as the change in urine isofuran levels (P = 0.04) was significantly greater in AKI subjects. In addition, change in peak plasma isofuran levels correlated not only with peak free plasma hemoglobin concentrations (r² = 0.39, P = 0.001) but also with peak change in serum creatinine (r² = 0.20, P = 0.01). Postoperative AKI is associated with both enhanced intraoperative hemeprotein release and enhanced lipid peroxidation. The correlations among hemoglobinemia, lipid peroxidation, and AKI indicate a potential role for hemeprotein-induced oxidative damage in the pathogenesis of postoperative AKI.
急性肾损伤（AKI）经常影响接受心肺旁路手术的患者，并且独立预测死亡。血红蛋白血症和肌红蛋白尿血症都是术后 AKI 的独立预测因素。游离血红素蛋白释放到循环中会导致肾脏氧化损伤。本研究检验了以下假设：术后 AKI 与术中血红素蛋白释放增加和脂质过氧化作用增强有关，通过测量 F₂-异前列腺素和异呋喃来评估。在一项正在进行的围手术期他汀类药物治疗和 AKI 的随机试验中进行的病例对照研究中，我们比较了 10 例心脏手术 AKI 患者和 10 例风险匹配对照者的 F₂-异前列腺素和异呋喃水平与游离血红蛋白和肌红蛋白的血浆水平。AKI 组的血浆游离血红蛋白浓度峰值明显升高（289.0±37.8 与 104.4±36.5mg/dl，P=0.01），而两组间的血浆肌红蛋白浓度相似。血浆 F₂-异前列腺素和异呋喃水平的变化（重复测量方差分析，P=0.02 和 P=0.001）以及尿异呋喃水平的变化（P=0.04）在 AKI 组中均显著更大。此外，峰值血浆异呋喃水平的变化不仅与峰值游离血浆血红蛋白浓度相关（r²=0.39，P=0.001），而且与血清肌酐的峰值变化相关（r²=0.20，P=0.01）。术后 AKI 与术中血红素蛋白释放增加和脂质过氧化作用增强有关。血红蛋白血症、脂质过氧化作用和 AKI 之间的相关性表明血红素蛋白诱导的氧化损伤在术后 AKI 的发病机制中可能发挥作用。
