多项生物学标志物联合检测对心脏术后急性肾损伤早期诊断的价值
다항생물학표지물연합검측대심장술후급성신손상조기진단적개치
Value of joint detection of multiple biomarkers on early diagnosis of acute kidney injury after cardiac surgery
  • 万方数据
    中国医药 중국의약
    China Medicine
    2015年 11期 1613-1617 ,共5页

    王恒进%李楠%刘金春%万骋%蒋春明%葛敏%王笑云%何劲松%张苗

    왕항진%리남%류금춘%만빙%장춘명%갈민%왕소운%하경송%장묘

    急性肾损伤%心脏手术%生物学标志物 急性腎損傷%心髒手術%生物學標誌物
    급성신손상%심장수술%생물학표지물
    Acute kidney injury%Cardiac surgery%Biomarkers
    目的 探讨尿金属基质蛋白酶组织抑制剂2(TIMP-2)、胰岛素样生长因子结合蛋白7(IGFBP-7)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)联合检测在心脏术后急性肾损伤(AKI)早期诊断中的价值.方法 选择2014年1-12月于南京大学医学院附属鼓楼医院行心脏手术患者311例,根据心脏术后是否发生AKI分为AKI组和非AKI组.术前和术后0、2、6、12、24、48、72 h收集血、尿标本检测并比较2组各时点血清肌酐、尿TIMP-2 、IGFBP-7与NGAL水平;以改善全球肾脏疾病预后组织的AKI定义和分级标准将AKI分为3级,比较AKI组各分级尿TIMP-2、 IGFBP-7与NGAL水平.采用受试者工作特征(ROC)曲线下面积评价3项生物学标志物单独及联合检测对AKI的诊断价值.结果 AKI发生率为19.0％ (59/311).AKI组59例,1级33例、2级17例、3级9例;非AKI组患者252例.术前和术后24、48、72 h,AKI组血清肌酐水平明显高于非AKI组[(69±13) μmol/L比(62 ± 12) μmol/L, (112 ±10) μmol/L比(102±11) μmol/L, (125±12) μmol/L比(93±10)μmol/L,(148±15) μmol/L比(95±11) μmol/L],差异有统计学意义(P＜0.05),2组其余各时点比较,差异无统计学意义(P＞0.05).2组术前尿TIMP-2/尿肌酐、NGAL/尿肌酐、IGFBP-7/尿肌酐水平比较差异无统计学意义(P＞0.05).术后2、6、12、24、48、72 h,非AKI组尿NGAL/尿肌酐、IGFBP-7/尿肌酐、TIMP-2/尿肌酐水平与术前比较[0.93(0.24,1.70) 、1.12(0.50,2.31) 、1.03(0.41,2.30) 、1.24(0.53,2.58) 、1.17 (0.51,2.40) 、1.89(0.78,2.94) μg/mg比0.87(0.31,1.68) μg,/mg, 3.18(1.79,7.51) 、3.27(1.86,6.93) 、3.59(1.73,7.11) 、3.08(1.59,6.34) 、2.65(1.24,5.49)、2.42(1.15,4.83) μg/mg比2.38(0.93,4.98) μg/mg, 0.11 (0.06,0.37)、0.13 (0.07,0.42) 、0.21(0.10,0.49)、0.17(0.09,0.38)、0.09(0.03,0.20)、0.06(0.02,0.17) μg/mg比0.05(0.01,0.14) μg/mg],差异无统计学意义(P ＞0.05) ,AKI组明显高于术前[7.68(3.46,19.01) 、16.92 (7.63,40.68) 、12.04 (5.09,26.13) 、23.81(10.72,58.91) 、19.03(8.91,40.11)、28.96(13.07,62.35)μg/mg比0.94 (0.42,2.33) μg/mg, 19.84 (2.61,40.37) 、41.56 (5.18,75.04)、62.18 (8.59,131.29)、29.33(4.81,60.27)、21.85(3.47,43.68)、10.26(2.09,21.73) μg/mg比2.57(0.61,5.19)μg/mg,0.52(0.10,1.49) 、1.15 (0.32,2.16) 、1.73 (0.46,3.01) 、1.27(0.31,2.39) 、1.09(0.31,2.17)、0.41(0.15,1.03)μg/mg比0.07(0.02,0.18) μg/mg],且AKI组明显高于非AKI组,差异有统计学意义(P＜0.05).AKI组尿NGAL/尿肌酐、IGFBP-7/尿肌酐、TIMP-2/尿肌酐水平随着肾脏损伤程度的加重而明显升高,2、3级明显高于1级[16.04 (7.12,37.96) 、23.51(9.25,48.01) μg/mg比5.59(2.91,12.04)μg/mg,40.21(5.07,73.92) 、61.30(8.41,127.35) μg/mg比13.06(1.72,26.57) μg/mg,1.14 (0.28,1.99)、1.68 (0.39,3.17) μg/mg比0.34 (0.09,0.72) μg/mg],差异均有统计学意义(P＜0.05).术后2h尿TIMP-2、IGFBP-7、NGAL诊断心脏术后AKI的ROC曲线下面积分别为0.77、0.81、0.69;三者联合检测,诊断敏感度和特异度分别为0.871和0.866,ROC曲线下面积为0.85,明显高于单独检测,差异有统计学意义(P＜0.05).结论 尿TIMP-2、IGFBP-7与NGAL可以作为早期诊断心脏术后AKI的敏感指标,三者联合检测可提高诊断AKI的效能.
    목적 탐토뇨금속기질단백매조직억제제2(TIMP-2)、이도소양생장인자결합단백7(IGFBP-7)화중성립세포명효매상관지질운재단백(NGAL)연합검측재심장술후급성신손상(AKI)조기진단중적개치.방법 선택2014년1-12월우남경대학의학원부속고루의원행심장수술환자311례,근거심장술후시부발생AKI분위AKI조화비AKI조.술전화술후0、2、6、12、24、48、72 h수집혈、뇨표본검측병비교2조각시점혈청기항、뇨TIMP-2 、IGFBP-7여NGAL수평;이개선전구신장질병예후조직적AKI정의화분급표준장AKI분위3급,비교AKI조각분급뇨TIMP-2、 IGFBP-7여NGAL수평.채용수시자공작특정(ROC)곡선하면적평개3항생물학표지물단독급연합검측대AKI적진단개치.결과 AKI발생솔위19.0％ (59/311).AKI조59례,1급33례、2급17례、3급9례;비AKI조환자252례.술전화술후24、48、72 h,AKI조혈청기항수평명현고우비AKI조[(69±13) μmol/L비(62 ± 12) μmol/L, (112 ±10) μmol/L비(102±11) μmol/L, (125±12) μmol/L비(93±10)μmol/L,(148±15) μmol/L비(95±11) μmol/L],차이유통계학의의(P＜0.05),2조기여각시점비교,차이무통계학의의(P＞0.05).2조술전뇨TIMP-2/뇨기항、NGAL/뇨기항、IGFBP-7/뇨기항수평비교차이무통계학의의(P＞0.05).술후2、6、12、24、48、72 h,비AKI조뇨NGAL/뇨기항、IGFBP-7/뇨기항、TIMP-2/뇨기항수평여술전비교[0.93(0.24,1.70) 、1.12(0.50,2.31) 、1.03(0.41,2.30) 、1.24(0.53,2.58) 、1.17 (0.51,2.40) 、1.89(0.78,2.94) μg/mg비0.87(0.31,1.68) μg,/mg, 3.18(1.79,7.51) 、3.27(1.86,6.93) 、3.59(1.73,7.11) 、3.08(1.59,6.34) 、2.65(1.24,5.49)、2.42(1.15,4.83) μg/mg비2.38(0.93,4.98) μg/mg, 0.11 (0.06,0.37)、0.13 (0.07,0.42) 、0.21(0.10,0.49)、0.17(0.09,0.38)、0.09(0.03,0.20)、0.06(0.02,0.17) μg/mg비0.05(0.01,0.14) μg/mg],차이무통계학의의(P ＞0.05) ,AKI조명현고우술전[7.68(3.46,19.01) 、16.92 (7.63,40.68) 、12.04 (5.09,26.13) 、23.81(10.72,58.91) 、19.03(8.91,40.11)、28.96(13.07,62.35)μg/mg비0.94 (0.42,2.33) μg/mg, 19.84 (2.61,40.37) 、41.56 (5.18,75.04)、62.18 (8.59,131.29)、29.33(4.81,60.27)、21.85(3.47,43.68)、10.26(2.09,21.73) μg/mg비2.57(0.61,5.19)μg/mg,0.52(0.10,1.49) 、1.15 (0.32,2.16) 、1.73 (0.46,3.01) 、1.27(0.31,2.39) 、1.09(0.31,2.17)、0.41(0.15,1.03)μg/mg비0.07(0.02,0.18) μg/mg],차AKI조명현고우비AKI조,차이유통계학의의(P＜0.05).AKI조뇨NGAL/뇨기항、IGFBP-7/뇨기항、TIMP-2/뇨기항수평수착신장손상정도적가중이명현승고,2、3급명현고우1급[16.04 (7.12,37.96) 、23.51(9.25,48.01) μg/mg비5.59(2.91,12.04)μg/mg,40.21(5.07,73.92) 、61.30(8.41,127.35) μg/mg비13.06(1.72,26.57) μg/mg,1.14 (0.28,1.99)、1.68 (0.39,3.17) μg/mg비0.34 (0.09,0.72) μg/mg],차이균유통계학의의(P＜0.05).술후2h뇨TIMP-2、IGFBP-7、NGAL진단심장술후AKI적ROC곡선하면적분별위0.77、0.81、0.69;삼자연합검측,진단민감도화특이도분별위0.871화0.866,ROC곡선하면적위0.85,명현고우단독검측,차이유통계학의의(P＜0.05).결론 뇨TIMP-2、IGFBP-7여NGAL가이작위조기진단심장술후AKI적민감지표,삼자연합검측가제고진단AKI적효능.
    Objective To assess the value of joint detection of urinary tissue inhibitor of matrix Metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP-7) and neutrophil gelatinase associated lipocalin (NGAL) in early diagnosis of acute kidney injury (AKI) after cardiac surgery.Methods A total of 311 patients who underwent cardiac surgery firom January to Decemeber in 2014 were enrolled and divided into AKI group and non-AKI group.The levels of serum creatinine (SCr), the levels of urinary creatinine (UCr), TIMP-2, IGFBP-7 and NGAL were measured 0, 2, 6, 12, 24, 48 and 72 h after cardiac surgery.According to the guideline of KDIGO (Kidney Disease : Improving Global Outcomes), the AKI was classified into stage 1, 2 and 3, the urinary TIMP-2, IGFBP-7 and NGAL were compared between different stages.The values of joint detection and single detection of above biomarkers in diagnosing AKI were analyzed through receiver operating characteristic curve (ROC).Results AKI occurred within 72 h after cardiac surgery in 59 patients, with incidence of 19.0％;there were 33 cases of stage 1, 17 cases of stage 2, and 9 cases of stage 3.The SCr in AKI group were significantly higher than that in non-AKI group before operation and 24, 48, 72 h after operation [(69 ± 13) μmol/L vs (62 ± 12) μmol/L, (112 ± 10) μmol/L vs (102 ± 11) μmol/L, (125 ± 12) μmol/L vs (93 ± 10) μmol/L, (148 ± 15) μmol/L vs (95 ± 11) μmol/L] (P ＜0.05), while it was not significantly different at other time points (P ＞ 0.05).The urinary TIMP-2/UCr, urinary NGAL/UCr, urinary IGFBP-7/UCr were no significantly different between groups before operation (P ＞ 0.05).Compared with those before operation, 2, 6, 12, 24, 48, 72 h after operation, the urinary NGAL/UCr, urinary IGFBP-7/UCr, urinary TIMP-2/UCr were not significantly changed in non-AKI group [0.93 (0.24, 1.70), 1.12 (0.50, 2.31), 1.03 (0.41, 2.30), 1.24 (0.53, 2.58), 1.17 (0.51, 2.40), 1.89 (0.78, 2.94) μg/mg vs 0.87 (0.31, 1.68) μg/mg, 3.18 (1.79, 7.51), 3.27 (1.86, 6.93), 3.59 (1.73, 7.11), 3.08 (1.59, 6.34), 2.65 (1.24, 5.49), 2.42 (1.15, 4.83) μg/mg vs 2.38 (0.93, 4.98) μg/mg, 0.11 (0.06, 0.37), 0.13 (0.07, 0.42), 0.21 (0.10,0.49), 0.17 (0.09, 0.38), 0.09 (0.03,0.20), 0.06 (0.02, 0.17) μg/mg vs 0.05 (0.01, 0.14) μg/mg] (P ＞ 0.05), while were significantly increased in AKI group [7.68 (3.46, 19.01), 16.92 (7.63, 40.68), 12.04 (5.09, 26.13), 23.81 (10.72, 58.91), 19.03 (8.91, 40.11), 28.96 (13.07, 62.35) μg/mg vs 0.94 (0.42, 2.33) μg/mg, 19.84 (2.61, 40.37), 41.56 (5.18, 75.04), 62.18 (8.59, 131.29), 29.33 (4.81, 60.27), 21.85 (3.47, 43.68), 10.26 (2.09, 21.73) μg/mg vs2.57 (0.61, 5.19) μg/mg, 0.52 (0.10, 1.49), 1.15 (0.32, 2.16), 1.73 (0.46, 3.01), 1.27 (0.31, 2.39), 1.09 (0.31, 2.17), 0.41 (0.15, 1.03) μg/mg vs 0.07 (0.02, 0.18) μg/mg], and they were significantly higher in AKI group than those in non-AKI group (P ＜ 0.05).In AKI group, the urinary NGAL/UCr, urinary IGFBP-7/UCr, urinary TIMP-2/UCr were increased with the severity of kidney damage, significantly higher in stage 2 and 3 compared with those in stage 1 [16.04 (7.12, 37.96), 23.51 (9.25, 48.01) μg/mg vs 5.59 (2.91, 12.04) μg/mg, 40.21 (5.07, 73.92), 61.30 (8.41, 127.35) μg/mg vs 13.06 (1.72, 26.57) μg/mg, 1.14 (0.28, 1.99), 1.68 (0.39, 3.17) μg/mg vs 0.34 (0.09, 0.72) μg/mg] (P ＜ 0.05).The area under ROC curves (AUC) of urinary TIMP-2, IGFBP-7 and NGAL was 0.77, 0.81,0.69, respectively.The sensitivity and specificity of joint detection in diagnosing AKI was 0.871 and 0.866;the AUC of joint detection was 0.85, significantly greater than that of single index detection (P ＜ 0.05).Conclusion The urine TIMP-2, IGFBP-7 and NGAL are sensitive in early diagnosing AKI after cardiac surgery;joint detection can improve the predictive value.
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