江潔龍，蘇克亮，袁園，蘭雷，黃珍珍，彭麗

(安徽醫(yī)科大學(xué)附屬省立醫(yī)院、安徽省立醫(yī)院腎內(nèi)科，合肥 230001)

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·論著·

尿腎損傷分子-1在急性腎損傷診斷中的價(jià)值

江潔龍，蘇克亮，袁園，蘭雷，黃珍珍，彭麗

(安徽醫(yī)科大學(xué)附屬省立醫(yī)院、安徽省立醫(yī)院腎內(nèi)科，合肥 230001)

[摘要]目的探討尿腎損傷分子-1(Kim-1)檢測(cè)在急性腎損傷(AKI)診斷中的價(jià)值。方法選擇確診的AKI患者71例作為AKI組，并選擇同時(shí)期健康體檢者30例為健康對(duì)照組，分別檢測(cè)尿Kim-1及血肌酐(Scr)水平。結(jié)果AKI組Scr、尿Kim-1較健康對(duì)照組明顯升高(P<0.01)，與健康對(duì)照組比較，Scr、尿Kim-1在AKI 1期、2期、3期均明顯升高(P<0.01)，與AKI 1期比較，Scr、尿Kim-1在AKI 2期、3期均明顯升高(P<0.01)，與AKI 2期比較，Scr及尿Kim-1在AKI 3期均明顯升高(P<0.01)；尿Kim-1與Scr之間具有明顯相關(guān)性(r=0.842，P<0.01)；尿Kim-1 ROC曲線下面積為0.915。結(jié)論尿Kim-1在AKI患者中排泄升高，對(duì)AKI具有診斷價(jià)值，可能為診斷AKI的敏感指標(biāo)。

[關(guān)鍵詞]急性腎損傷;診斷技術(shù),泌尿科;糖蛋白類

急性腎損傷(AKI)是一種由多種原因引起、以腎功能急劇惡化并導(dǎo)致腎臟無法排泄尿毒素和維持電解質(zhì)和水的平衡為特點(diǎn)的發(fā)病率高、臨床常見的綜合征[1]。在急性損傷早期進(jìn)行有效干預(yù)可以逆轉(zhuǎn)該病進(jìn)展[2]。因此，尋找早期診斷AKI的生物標(biāo)記物并對(duì)該病早期診斷、早期治療是目前研究的熱點(diǎn)。國(guó)外已有研究表明[3-6]，腎損傷分子-1(Kim-1)對(duì)急性腎損傷可能具有早期診斷價(jià)值。本文通過觀察不同時(shí)期AKI患者及非AKI患者中尿Kim-1變化情況，評(píng)價(jià)尿Kim-1對(duì)AKI的早期診斷價(jià)值。

1對(duì)象與方法

1.1研究對(duì)象選擇2011年1月至2012年12月在我院住院確診的急性腎損傷患者71例作為AKI組(AKI 1期23例、AKI 2期25例、AKI 3期23例)，其中男39例，女32例；年齡 19~76周歲，平均(43.7±14.0)歲。選擇同時(shí)期我院體檢中心健康體檢者30例為健康對(duì)照組，均無急慢性腎臟病、高血壓病、糖尿病及其他嚴(yán)重疾病，近期未服用腎毒性藥物，其中男18例，女12例；年齡19~68周歲，平均(40.3±13.5)歲。AKI組及健康對(duì)照組患者年齡及性別均差異無統(tǒng)計(jì)學(xué)意義。

1.2納入與排除標(biāo)準(zhǔn)納入標(biāo)準(zhǔn)即為AKI診斷標(biāo)準(zhǔn)：參照2005年9月荷蘭阿姆斯特丹國(guó)際急性腎損傷網(wǎng)絡(luò)(AKIN)第一次會(huì)議急性腎損傷專家共識(shí)小組制定的AKI標(biāo)準(zhǔn)。排除標(biāo)準(zhǔn)：(1)住院時(shí)間小于24 h；(2)終末期腎臟病行維持性透析患者；(3)腎移植患者；(4)再次住院患者；(5)年齡小于18周歲。

1.3標(biāo)本收集所有入選的研究對(duì)象均留取新鮮晨尿 10 mL，以 1000 r/min離心10 min后取上清液進(jìn)行檢測(cè)，同時(shí)留取血標(biāo)本5 mL送檢。

1.4主要儀器、試劑及檢測(cè)方法采用的儀器為上?？迫A KHB-ST-360酶標(biāo)儀、日本日立HITACHI7600-020全自動(dòng)生化分析儀。尿Kim-1采用酶聯(lián)免疫吸附法(ELISA)檢測(cè)，Kim-1試劑盒由上海信裕生物科技有限公司提供，實(shí)驗(yàn)方法按試劑盒說明書操作。

1.5統(tǒng)計(jì)學(xué)處理使用SPSS15.0軟件進(jìn)行數(shù)據(jù)分析,AKI組與健康對(duì)照組間比較采用t檢驗(yàn)，AKI各分期組及健康對(duì)照組組間比較采用One-way ANOVA分析；繪制受試者工作特征(ROC)曲線并計(jì)算選擇最佳的診斷界限值。計(jì)數(shù)資料組間比較采用χ2檢驗(yàn)。

2結(jié)果

2.1健康對(duì)照組與AKI組各項(xiàng)指標(biāo)水平比較見表1。

表1　健康對(duì)照組與AKI組各項(xiàng)指標(biāo)水平比較±s)

注：與健康對(duì)照組比較，aP<0.01；與AKI 1期組比較，bP<0.01；與AKI 2期組比較，cP<0.01

2.2Kim-1與Scr相關(guān)性Kim-1與Scr相關(guān)系數(shù)為0.842，P<0.01，見圖1。

2.3尿Kim-1 ROC曲線下面積及診斷點(diǎn)尿Kim-1的ROC曲線下面積(AUC)為0.915，95% 的可信區(qū)間為0.853～0.978，以73.58 μg/L 作為AKI的診斷界限時(shí)，敏感性和特異性分別為93.0%和83.3%，見圖2。

圖1　尿與Scr相關(guān)性

圖2　尿Kim-1 ROC曲線下面積及診斷點(diǎn)

3討論

Kim-1是由腎臟近曲小管上皮細(xì)胞分泌一種跨膜1型糖蛋白，其中包含6-半胱氨酸域，屬于免疫球蛋白基因超家族。它在正常肝、腎、脾組織中微量表達(dá)，而在受損后再生的近曲小管上皮細(xì)胞中表達(dá)明顯增強(qiáng)。動(dòng)物研究表明，Kim-1的外功能區(qū)斷裂后產(chǎn)物能夠通過尿中排出，因此檢測(cè)尿中Kim-1水平可以間接評(píng)價(jià)腎臟損傷的情況，且已有研究表明，Kim-1對(duì)急性腎損傷具有早期診斷價(jià)值[7-10]。本研究發(fā)現(xiàn)，尿Kim-1在AKI組較健康對(duì)照組明顯升高，且在AKI 1期、2期、3期逐漸升高，其兩兩相互比較差異均有統(tǒng)計(jì)學(xué)意義；尿Kim-1與Scr具有明顯相關(guān)性(r=0.842，P<0.01)；尿Kim-1的ROC AUC為0.915，以73.58 μg/L 作為AKI的診斷界限時(shí)，敏感性和特異性分別為93.0% 和83.3%，故尿Kim-1可能為診斷AKI的敏感指標(biāo)。

同時(shí)，已有研究表明，目前常用的生物學(xué)標(biāo)記物診斷AKI效能不同。Liangos等[11]比較了Kim-1、N-乙酰-β-D-氨基葡萄糖苷酶、中性粒細(xì)胞明膠酶相關(guān)脂質(zhì)運(yùn)載蛋白、白細(xì)胞介素-18、胱抑素C 、α1-微球蛋白等6種生物學(xué)標(biāo)記物對(duì)AKI的診斷價(jià)值，發(fā)現(xiàn)Kim-1診斷AKI的AUC最大，為 0.78，其 95% 可信區(qū)間 0.64~0.91。

綜上所述，尿Kim-1在AKI患者中明顯升高，且在AKI不同分期患者中差異有統(tǒng)計(jì)學(xué)意義，結(jié)合其ROC AUC及診斷敏感性及特異性，其對(duì)AKI可能具有診斷價(jià)值。

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The diagnostic value of urinary Kim-1 detection in acute kidney injury

JiangJielong,SuKeliang,YuanYuan,LanLei,HuangZhenzhen,PengLi

(DepartmentofNephrology,AnhuiProvincialHospitalAffiliatedtoAnhuiMedicalUniversity,Hefei230001,China)

[Abstract]ObjectiveTo explore the diagnostic value of urinary Kidney injury molecule-1 (Kim-1) detection in patients with acute kidney injury (AKI). MethodSeventy-one patients with AKI were selected as the study group (AKI group), and 30 healthy individuals were enrolled as the control group. The levels of urinary Kim-1 and serum creatinine (Scr) were measured respectively.ResultsThe urinary Kim-1 and Scr were increased significantly (P<0.01) in AKI group when compared with the control group. The urinary Kim-1 and Scr increased significantly (P<0.01) in AKI stage 1, 2 and 3 in AKI group when compared with control group. The urinary Kim-1 and Scr were increased significantly (P<0.01) in AKI stage 2 and 3 when compared with stage 1. The urinary Kim-1 and Scr were increased significantly (P<0.01) in AKI stage 3 when compared with AKI stage 2. There was significant relationship between the urinary Kim-1 and Scr. The area under the receiver operating characteristics curve in the urinary Kim-1 was 0.915. ConclusionThe urinary Kim-1 excretion increases significantly in AKI group. It maybe has diagnostic value in AKI and used as a sensitive target diagnostic criteria for AKI.

[Key words]Acute kidney injury;Diagnostic techniques,urological;Glycoproteins

(收稿日期：2014-07-16)

Corresponding author:Su Keliang, Email：sukl8@163.com

中圖分類號(hào)：R692.5

文獻(xiàn)標(biāo)識(shí)碼：A

DOI:10.3969/J.issn.1672-6790.2015.03.008

通信作者：蘇克亮，博士，副主任醫(yī)師，Email：sukl8@163.com

作者簡(jiǎn)介：江潔龍，博士，主治醫(yī)師，Email：jiangjl2013@126.com

基金項(xiàng)目：安徽省科技計(jì)劃項(xiàng)目(10021403082)