尿中性粒细胞明胶酶相关载脂蛋白和肝型脂肪酸结合蛋白对肝移植术后急性肾损伤的早期诊断价值

目的 探讨尿中性粒细胞明胶酶相关载脂蛋白（NGAL）和肝型脂肪酸结合蛋白（L-FABP）在肝移植术后急性肾损伤（AKI）中的早期诊断价值。 方法 前瞻性收集2007至2008年间25例肝移植患者术前、门静脉开放后2、4、6、12、24、48、72和120 h的血液和尿液标本，检测Scr和尿NGAL及L-FABP水平。根据急性肾损伤网（AKIN）标准中的Scr标准将患者分为AKI组和非AKI组。观察两组各时间点尿NGAL、尿L-FABP和Scr水平的动态变化；运用受试者工作特征曲线（ROC）评价尿NGAL和L-FABP诊断AKI的精确性。 结果 25例患者中11例发生了术后AKI，两组患者术前、术中及术后情况差异无统计学意义。术后24 h AKI组与非AKI组的Scr差异有统计学意义(90.48±50.32) 比（59.84±14.72） μmol/L，P < 0.05]。AKI组与非AKI组术后2～120 h尿L-FABP均显著升高，4 h时差异有统计学意义2361.41（1036.89~4048.93） ng/mgCr比5246.97（2406.33~7688.21） ng/mgCr，P < 0.05]。AKI组术后2、4、6 h尿NGAL均显著高于非AKI组，差异有统计学意义 69.02（29.79~237.29）比22.94（8.69~46.23） ng/mgCr，29.34（16.06~536.91）比 12.66（8.91~22.78） ng/mgCr和34.23（11.47~81.26）比11.84（6.57~20.10） ng/mgCr，均P < 0.05]。ROC曲线下面积（AUC）结果显示，与尿L-FABP相比（当4 h截断点为3451.75 ng/mgCr时，AUC为0.760），尿NGAL对早期诊断AKI具有更高的敏感性和特异性（2、4、6 h的截断点分别为43.02、26.97和17.19 ng/mgCr时，AUC分别为0.766、0.773和0.773）。 结论 尿NGAL在肝移植术后早期AKI的诊断上表现出较高的敏感性和特异性，也许能作为肝移植术后AKI早期诊断的生物学标志物，但仍需要大样本的临床研究加以证实。

Value of urine NGAL and L-FABP in early diagnosis of acute kidney injury after liver transplantation

Objective To investigate the value of urinary neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding proteins (L-FABP) in early diagnosis of acute kidney injury (AKI) after liver transplantation. Methods During 2007-2008, 25 liver transplant recipients were recruited. Blood and urinary samples were collected before operation and at 2, 4, 6, 12, 24, 48, 72, 120 h after portal vein opening, and used to determine serum creatinine (Scr), as well as urinary NGAL and L-FABP, which were normalized to urinary creatinine. According to the Acute Kidney Injury Network(AKIN) criteria of AKI, all the patients were divided into AKI and non-AKI groups. Standard statistics were used along with ROC analysis to evaluate the diagnose value of selected markers. Results There were no significant differences in clinical parameters between non-AKI (n=14) and AKI (n=11) groups. Both groups had a transient rise in Scr 2-12 hours after surgery, but the rise lasted longer in AKI patients (2-24 hours). While urinary L-FABP rose transiently in both groups 2-120 hours following surgery, urinary NGAL was only slightly elevated at 2 h in the non-AKI group, but rose and stayed high from 2 to 6 h in the AKI group. ROC analysis revealed that NGAL (cut-off 43.02, 26.97 and 17.19 ng/mgCr, AUC 0.766, 0.773 and 0.773 at 2, 4 and 6 h, respectively) was better than L-FABP (cut-off 3451.75 ng/mgCr, AUC 0.760 at 4 h). Conclusion Urinary NGAL appears to be a sensitive and specific marker of AKI in liver transplant recipients, but these data need to be validated in larger prospective studies.