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

基本信息

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

项目摘要

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

尽管急性肾脏损伤（AKI）是ICU领域治疗的患者预后的最重要预测指标，但在血清创造兴起之前，没有敏感的生物标志物可以诊断AKI。 Recently, several urinary biomarkers such as NGAL, IL-18, KIM-1, NHE3, KC, and L-FABP are reported as a candidate of new sensitive biomarkers of AKI.We reported that midkine(MK), a heparin-binding growth factor, was induced in the disseased kidneys and promoted chemotaxis of leukocytes in the animal models of an ischemic renal reperfusion伤害（Sato W.等，J Immunol 2001; 167：3463-3469）。缺血性损伤后主要在近端管中检测到MK的增强表达。在这里，我们评估了人类MK是否从肾小管上皮细胞中脱落到尿液中，并且可以作为人类急性肾脏损伤的潜在尿生物标志物。西方印迹分析表明，在培养物中，MK在培养培养基中的表达增加了……从培养物中发现了更多的ED ED ED ED ED ED ED -ED -ED -ED -ED -ED -HUMANE EPITHELIAL（HK2）细胞（HK2），而不是用Hkke hkk ber hkk，而不是HKK 2。细胞裂解物中MK表达没有差异。对于尿液MK的测量，583例患者，包括对照组（n = 33），患有不同形式的急性结核性坏死（n = 33）的患者（n = 33），以及其他慢性肾疾病的患者（n = 517），是研究的。通过酶联免疫测定确定尿MK水平。与其他慢性肾脏疾病或对照组的患者相比，ATN患者的尿MK水平明显更高。对于MK尿液的浓度，用于诊断ATN的接收器操作特征（ROC）曲线分析表明，敏感性为97.0％，特异性为91.1％，截止值为70.0 pg/ml.我们已经确认，尿液MK水平是一种敏感的生物标志物，可以在早期诊断中诊断为早期诊断。我们获得了专利（2008-048954，参考：K20070222），用于“ AKI早期诊断的临床检查：尿液MK测量”。较少的