Clinical implication of urinary midkine as a sensitive biomarker of acute kidney injury

尿中期因子作为急性肾损伤敏感生物标志物的临床意义

• 批准号: 18390247
• 负责人: MATSUO Seiichi
• 金额: $ 10.57万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390247/
• 关键词: Growth Factor; Biomarker; tubular injury; ischemia; proteinuria; acute kidney injury; midkine

Although acute kidney injury (AKI) is the most important predictor of the prognosis of the patients treated in the field of ICU, there have been no sensitive biomarkers to diagnose AKI before the rising of serum creatinine. Recently, several urinary biomarkers such as NGAL, IL-18, KIM-1, NHE3, KC, and L-FABP are reported as a candidate of new sensitive biomarker of AKI.We reported that midkine(MK), a heparin-binding growth factor, was induced in the diseased kidneys and promoted chemotaxis of leukocytes in the animal models of an ischemic renal reperfusion injury(Sato W., et. al., J Immunol 2001 ; 167 : 3463-3469). The enhanced expression of MK was detected mainly in the proximal tubules after ischemic injuries. Here, we evaluated whether human MK is shed into urine from the tubular epithelial cells, and may serve as a potent urinary biomarker of acute kidney injuries in human.Western blot analysis showed that the increased expression of MK was detected in the culture media from cultur … More ed human tubular epithelial(HK2)cells treated with hypoxia, but not from HK2 cells treated with 20 μM BSA. There were no differences in the MK expression in the cell lysates.For the measurement of urinary MK, 583 patients, including controls (n=33), patients with different forms of acute tubular necrosis (ATN) (n=33), and patients with other chronic renal diseases(n= 517), were studied. Urinary MK level was determined by enzyme-linked immunoassay.The urinary MK levels were significantly higher in patients with ATN compared to levels in patients with other chronic renal diseases or controls. For concentration in urine of MK, the receiver-operating characteristic(ROC)curve analysis for diagnosis of ATN showed that sensitivity was 97.0 %, and specificity was 91.1 % for a cut-off value of 70.0 pg/ml.We have confirmed that urinary MK level serves as a sensitive biomarker of ATN facilitating the early diagnosis of the disease. We obtained the patent(2008-048954, Ref : K20070222)for "Clinical examination for the early diagnosis of AKI : Urinary MK measurement". Less

急性肾损伤（acute kidney injury，阿基）是重症监护病房（ICU）中最重要的预后指标，但在血肌酐升高之前，尚无敏感的生物标志物诊断阿基。最近，NGAL、IL-18、KIM-1、NHE 3、KC和L-FABP等几种尿液生物标志物被报道为阿基新的敏感生物标志物的候选者。我们报道了中间因子（MK），一种肝素结合生长因子，在缺血性肾再灌注损伤动物模型中，在患病肾脏中被诱导并促进白细胞的趋化性（Sato W.，et.例如，J Immunol 2001 ; 167：3463-3469）。缺血损伤后MK表达增强主要在近端肾小管。在此，我们评估了人MK是否从肾小管上皮细胞脱落到尿液中，并可能作为人类急性肾损伤的有效尿液生物标志物。Western印迹分析显示，在培养的肾小管上皮细胞的培养基中检测到MK的表达增加。 ...更多信息 艾德对缺氧处理的人肾小管上皮细胞（HK 2）进行了诱导，但对20 μM BSA处理的HK 2细胞未进行诱导。尿MK测定包括正常对照组（n=33）、急性肾小管坏死（ATN）组（n = 33）和其他慢性肾脏疾病组（n= 517）共583例患者。采用酶联免疫法测定尿MK水平，ATN患者尿MK水平显著高于其他慢性肾脏疾病患者和对照组。尿MK浓度诊断ATN的受试者工作特征（ROC）曲线分析显示，以70.0 pg/ml为界值，敏感性为97.0%，特异性为91.1%，提示尿MK水平可作为ATN的敏感生物标志物，有助于ATN的早期诊断。我们获得了专利（2008-048954，参考号：K20070222）“用于阿基早期诊断的临床检查：尿MK测量”。少

项目成果

A protein toxin from the sea anemone Phyllodiscus semoni targets the kidney and causes a severe renal injury with predominant glomerular endothelial damage

• DOI: 10.2353/ajpath.2007.060984
• 发表时间: 2007-08-01
• 期刊: AMERICAN JOURNAL OF PATHOLOGY
• 影响因子: 6
• 作者: Mizuno, Masashi;Nozaki, Masatoshi;Matsuo, Seiichi
• 通讯作者: Matsuo, Seiichi

Effects of olprinone, a phosphodiesterase III inhibitor, on ischemic acute renal failure

• DOI: 10.1111/j.1442-2042.2007.01689.x
• 发表时间: 2007-03-01
• 期刊: INTERNATIONAL JOURNAL OF UROLOGY
• 影响因子: 2.6
• 作者: Anas, Chabouk;Ozaki, Takenori;Matsuo, Seiichi
• 通讯作者: Matsuo, Seiichi

High levels of complement C3a receptor in the glomeruli in lupus nephritis

• DOI: 10.1053/j.ajkd.2007.02.271
• 发表时间: 2007-05-01
• 期刊: AMERICAN JOURNAL OF KIDNEY DISEASES
• 影响因子: 13.2
• 作者: Mizuno, Masashi;Blanchin, Stephanie;Matsuo, Seiichi
• 通讯作者: Matsuo, Seiichi

Adipose Derived Stromal Cells Cultured in Low-Serum Media Secrete High Levels of Cytokines and Ameliorate Acute Kidney Injury

在低血清培养基中培养的脂肪源性基质细胞分泌高水平的细胞因子并改善急性肾损伤

• 发表时间: 2007
• 作者: Takenori Ozaki;Shoichi Maruyama;Tatsuto Watanabe;Shigejiro Iwashima;Kaoru Yasuda;Tokunori Yamamoto;Yasuo Kitagawa;Momokazu Gotoh;Yukio Yuzawa;Seiichi Matsuo
• 通讯作者: Seiichi Matsuo

Midkine is involved in tubulointerstitial inflammation associated with diabetic nenhronathy

中期因子参与与糖尿病肾病相关的肾小管间质炎症

• 发表时间: 2007
• 期刊: Lab Invest 87(9)
• 作者: Kosugi;T
• 通讯作者: T