Nagaya Hiroshi, Kosugi Tomoki, Maeda-Hori Mayuko, Maeda Kayaho, Sato Yuka, Kojima Hiroshi, Hayashi Hiroki, Kato Noritoshi, Ishimoto Takuji, Sato Waichi, Yuzawa Yukio, Matsuo Seiichi, Kadomatsu Kenji, Maruyama Shoichi
Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Clin Exp Nephrol. 2014 Oct;18(5):746-54. doi: 10.1007/s10157-013-0916-3. Epub 2013 Dec 4.
Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI.
Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary L-fatty acid-binding protein (L-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining.
In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary L-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary L-FABP.
CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication.
急性肾小管坏死(ATN)是一种内在性急性肾损伤(AKI)形式,由持续性低灌注及随后的免疫系统激活所致。一种糖基化跨膜蛋白,即CD147/基底膜蛋白,参与肾缺血和纤维化的发病机制。本研究调查了CD147是否能反映AKI患者的病理特征和肾功能障碍。
收集了2008年至2012年间接受肾活检的24例患者(12例对照和12例ATN患者)的血浆和随机尿样本。在另一项研究中,2004年纳入了接受开放手术治疗腹主动脉瘤(AAA)的患者。我们分别从7例AKI患者和33例非AKI患者中收集了尿和血浆样本。在这些实验中,测量了血浆和尿中CD147以及尿中L-脂肪酸结合蛋白(L-FABP)水平,并通过免疫染色检查了前者在肾脏中的表达。
在具有严重组织学特征的ATN活检组织中,CD147诱导显著存在于受损间质中的巨噬细胞和淋巴细胞等炎症细胞中,但不存在于代表萎缩的受损肾小管中。ATN患者的血浆和尿CD147水平均显著升高;与尿L-FABP相比,这两个值与肾功能障碍的相关性更大。在接受AAA开放手术的患者中,术后第1天AKI患者的尿和血浆CD147值显著高于非AKI患者,与尿L-FABP的情况相似。
CD147在检测AKI方面能力突出,可能有助于启动预防性药物治疗。