尿胰岛素样生长因子结合蛋白7和金属蛋白酶2组织抑制剂联合检测对心脏术后急性肾损伤早期诊断及预后的价值

Value of combined measurement of urine insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinase 2 in the early diagnosis and prognosis of cardiac surgery-associated acute kidney injury

目的评估尿胰岛素样生长因子结合蛋白7(insulin-like growth factor binding protein 7,IGFBP7)联合尿金属蛋白酶2组织抑制剂(tissue inhibitor of metalloproteinase 2,TIMP-2)对心脏手术相关急性肾损伤(cardiac surgery-associated acute kidney injury,CSA-AKI)的早期诊断和预后预测的价值。方法前瞻性收集2018年3月至2018年6月入住南京医科大学第一附属医院心脏大血管外科的心脏手术患者术后尿液,并监测血肌酐,将患者分为心脏术后急性肾损伤(acute kidney injury,AKI)组及非AKI组。收集患者的基本资料,预后信息包括住院透析、住院死亡、出院时肾功能完全恢复、术后1年死亡、进展为慢性肾脏病。采用酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)检测术后6 h、24 h、48 h尿液中IGFBP7和TIMP-2的水平,并同时测定尿肌酐(Cr)。通过绘制受试者工作特征曲线(ROC)及计算曲线下面积(AUC)评价尿[TIMP-2]·[IGFBP7](简称T^(*)I)及尿T^(*)I/尿Cr2对AKI的早期诊断和预后预测的价值。结果本研究共纳入74例患者,年龄(58.43±10.91)岁,男性47例(63.5%);其中24例(32.4%)发生AKI,10例(13.5%)为2~3期AKI。心脏术后AKI组患者尿T^(*)I在6 h、24 h时明显高于非AKI组(均P<0.05)。心脏术后24 h尿T^(*)I预测AKI的AUC为0.71(95%CI 0.59~0.81,P=0.001,截断值为0.020,敏感度79.2%,特异度56.0%),而预测2~3期AKI的AUC为0.85(95%CI 0.75~0.92,P<0.001,截断值为0.083,敏感度70.0%,特异度90.6%);尿肌酐校正的尿T^(*)I没有显示出更优的预测价值。此外,24 h尿T^(*)I预测CSA-AKI患者的不良住院结局、肾功能恢复和术后1年死亡的AUC分别为0.82(95%CI 0.71~0.90,P=0.001)、0.80(95%CI 0.66~0.86,P<0.001)和0.81(95%CI 0.70~0.89,P=0.047)。结论尿液中TIMP-2与IGFBP7的联合检测有望成为早期诊断CSA-AKI的生物标志物,在预测CSA-AKI的预后中具有一定临床价值。

Objective To evaluate the value of combined measurement of urinary insulin-like growth factor-binding protein 7(IGFBP7)and urinary metalloproteinase inhibitor-2(TIMP-2)in the early diagnosis and prognosis of cardiac surgery-associated acute kidney injury(CSA-AKI).Methods From March 2018 to June 2018,cardiac surgery patients admitted to the cardiac macrovascular surgery department of the First Affiliated Hospital of Nanjing Medical University were prospectively included,and the blood creatinine was monitored to observe the presence of acute kidney injury(AKI).The prognostic information of the patients was collected,including in-hospital dialysis,in-hospital death,complete recovery of kidney function at discharge,death in one year after surgery,and progression to chronic kidney disease.The levels of urine IGFBP7 and TIMP-2 at 6 h,24 h and 48 h after cardiac surgery were detected by enzyme linked immunosorbent assay(ELISA),and the urine creatinine(Cr)was also measured.Moreover,receiver operating characteristic curves(ROC)were plotted and the areas under the curves(AUC)were calculated to evaluate the predictive value and prognostic value of urinary[TIMP-2]·[IGFBP7](T^(*)I for short)and urine T^(*)I/urine Cr2 in CSA-AKI.Results A total of 74 patients with age of(58.43±10.91)years old and 47 males,were enrolled in this study,of which 24 cases(32.4%)had AKI and 10 cases(13.5%)had stage 2-3 AKI.Compared with the non-AKI group,the AKI group had significantly higher levels of urine T^(*)I levels at 6 h and 24 h(both P<0.05).The AUC of T^(*)I at 24 h predicting for AKI was 0.71(95%CI 0.59-0.81,P=0.001,cutoff value 0.020,sensitivity 79.2%,specificity 56.0%),while the AUC for stage 2-3 AKI was 0.85(95%CI 0.75-0.92,P<0.001,cutoff value 0.083,sensitivity 70.0%,specificity 90.6%).Urinary T^(*)I normalized for urinary creatinine excretion did not show better predictive value.In addition,of T^(*)I at 24 h predicting for poor hospitalization outcome,renal recovery,and one year postoperative death,the AUC was 0.82(95%CI 0.71-0.90,P=0.001),0.80(95%CI 0.66-0.86,P<0.001),and 0.81(95%CI 0.70-0.89,P=0.047),respectively.Conclusion The combined detection of TIMP-2 and IGFBP7 in urine is expected to be a biomarker for early diagnosis of CSA-AKI and has certain clinical value in predicting the prognosis of CSA-AKI.