DCD供肾灌注液生物标志物预测肾移植术后移植物功能延迟恢复的临床应用研究

Clinical application of biomarkers in DCD donor kidney perfusate for predicting delayed graft function after renal transplantation

目的探讨心脏死亡器官捐献(DCD)供肾静态冷保存(SCS)灌注液生物标志物预测肾移植受者术后发生移植物功能延迟恢复(DGF)的可行性。方法回顾性分析DCD供肾肾移植的64例受者和47例供者的临床资料。根据受者术后是否发生DGF分为DGF组(7例)与即刻肾功能恢复(IGF)组(57例),比较两组供肾SCS灌注液中4种生物标志物中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肝型脂肪酸结合蛋白(L-FABP)、白细胞介素-18(IL-18)、肾损伤分子-1(KIM-1)的水平并分析其与DGF的相关性,分析各生物标志物对肾移植受者术后发生DGF的预测价值。结果DCD供肾肾移植受者术后DGF的发生率为11%(7/64)。DGF组供肾灌注液的NGAL水平高于IGF组(P=0.009),供肾灌注液的NGAL水平与肾移植受者术后DGF的发生呈正相关(r=0.430,P<0.001)。受试者工作特征(ROC)曲线分析结果显示,灌注液中的NGAL和KIM-1水平升高对肾移植受者术后发生DGF具有一定的预测价值(均为P<0.05),当联合检测NGAL和KIM-1时,预测肾移植受者术后发生DGF的曲线下面积(AUC)为0.932[95%可信区间(CI)0.850~1.000],灵敏度为1.000,特异度为0.754(P<0.05)。结论DCD供肾SCS灌注液中的NGAL水平与肾移植受者术后DGF的发生存在相关性,联合检测灌注液中的NGAL和KIM-1水平可以较为准确地预测肾移植受者术后DGF的发生。

Objective To explore the feasibility of biomarkers in static cold storage(SCS)perfusate of donor kidney from donation after cardiac death(DCD)for predicting delayed graft function(DGF)after renal transplantation.Methods Clinical data of 64 recipients and 47 donors undergoing DCD renal transplantation were retrospectively analyzed.All recipients were divided into the DGF group(n=7)and immediate graft function(IGF)group(n=57)according to the incidence of postoperative DGF in the recipients.The levels of neutrophil gelatinase-associated lipocalin(NGAL),liver-type fatty acid-binding protein(L-FABP),interleukin-18(IL-18)and kidney injury molecule-1(KIM-1)in the SCS perfusate were statistically compared between two groups,and the correlation with DGF was analyzed.The predictive value of each biomarker in the occurrence of DGF in recipients after renal transplantation was analyzed.Results The incidence of DGF in the recipients undergoing DCD renal transplantation was 11%(7/64).The NGAL level in the donor kidney perfusate of the DGF group was significantly higher than that in the IGF group(P=0.009).The NGAL level in the donor kidney perfusate was positively correlated with the incidence of DGF in recipients after renal transplantation(r=0.430,P<0.001).The receiver operating characteristic(ROC)curve analysis showed that the increased levels of NGAL and KIM-1 in the perfusate yielded certain predictive value for DGF in recipients after renal transplantation(both P<0.05).The area under the curve(AUC)of combined detection of NGAL and KIM-1 for predicting DGF in recipients after renal transplantation was 0.932[95%confidence interval(CI)0.850-1.000].The sensitivity was calculated as 1.000 and 0.754 for the specificity(P<0.05).Conclusions The NGAL level in the SCS perfusate of DCD donor kidney is associated with the occurrence of DGF in recipients after renal transplantation.Combined detection of NGAL and KIM-1 levels in the perfusate may accurately predict the occurrence of DGF in recipients after renal transplantation.