Department of Anesthesiology, Anesthesiology Research Laboratories, College of Physicians and Surgeons, Columbia University, P&S Box 46 (PH-5), 630 West 168th Street, New York, NY 10032-3784, USA.
J Am Soc Nephrol. 2013 Feb;24(3):445-55. doi: 10.1681/ASN.2012090943. Epub 2013 Feb 7.
Elevated levels of plasma catecholamines accompany ischemic AKI, possibly contributing the inflammatory response. Renalase, an amine oxidase secreted by the proximal tubule, degrades circulating catecholamines and reduces myocardial necrosis, suggesting that it may protect against renal ischemia reperfusion injury. Here, mice subjected to renal ischemia reperfusion injury had significantly lower levels of renalase in the plasma and kidney compared with sham-operated mice. Consistent with this, plasma NE levels increased significantly after renal ischemia reperfusion injury. Furthermore, renal tubular inflammation, necrosis, and apoptosis were more severe and plasma catecholamine levels were higher in renalase-deficient mice subjected to renal ischemia reperfusion compared with wild-type mice. Administration of recombinant human renalase reduced plasma catecholamine levels and ameliorated ischemic AKI in wild-type mice. Taken together, these data suggest that renalase protects against ischemic AKI by reducing renal tubular necrosis, apoptosis, and inflammation, and that plasma renalase might be a biomarker for AKI. Recombinant renalase therapy may have potential for the prevention and treatment of AKI.
血浆儿茶酚胺水平升高伴随着缺血性急性肾损伤,可能有助于炎症反应。肾素酶,一种由近端肾小管分泌的胺氧化酶,降解循环中的儿茶酚胺并减少心肌坏死,表明它可能对肾缺血再灌注损伤具有保护作用。在这里,与假手术组相比,肾缺血再灌注损伤的小鼠血浆和肾脏中的肾素酶水平显著降低。与此一致的是,肾缺血再灌注损伤后血浆去甲肾上腺素水平显著升高。此外,与野生型小鼠相比,肾素酶缺乏的小鼠肾缺血再灌注后肾小管炎症、坏死和凋亡更严重,血浆儿茶酚胺水平更高。给予重组人肾素酶可降低野生型小鼠的血浆儿茶酚胺水平并改善缺血性急性肾损伤。综上所述,这些数据表明,肾素酶通过减少肾小管坏死、凋亡和炎症来保护缺血性急性肾损伤,而血浆肾素酶可能是急性肾损伤的生物标志物。重组肾素酶治疗可能具有预防和治疗急性肾损伤的潜力。