de Rooij Esther N M, van Duijl Tirsa T, Hoogeveen Ellen K, Romijn Fred P H T M, Dekker Friedo W, van Kooten Cees, Cobbaert Christa M, de Fijter Johan W
Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
Transpl Int. 2025 May 12;38:13818. doi: 10.3389/ti.2025.13818. eCollection 2025.
Recipients of donation after circulatory death (DCD) kidneys are at high risk for delayed graft function (DGF) due to severe ischemia-reperfusion injury. We compared urinary biomarkers in predicting the duration of DGF with the tubular function slope (TFS) as the gold standard. In 89 DCD kidney transplant recipients, urinary TIMP-2, IGFBP7, B2M, NGAL, KIM1, CXCL9, and UMOD were quantified by LC-MS/MS analysis on postoperative days (PODs) 1, 4 and 10. Interstitial fibrosis and tubular atrophy (IF/TA) were assessed with protocol biopsies at POD 10. TFS was calculated with Tc-MAG3 renography. Predictive performance was compared with AUCs from ROC analyses. Of all 89 recipients, 22% experienced no (<7), 22% mild (≥7-14), 29% moderate (≥14-<21) and 26% severe (≥21 days) fDGF. The OR for the presence of IF/TA was 1.9 (95% CI:0.4; 10.0) for mild to moderate and 15.0 (95% CI:2.7; 84.8) for severe compared to no fDGF. At POD 4, urinary NGAL and fractional NGAL excretion (FE-NGAL) outperformed TFS and other biomarkers in predicting fDGF with AUCs of 0.97, 0.98 and 0.92, respectively. At POD10, FE-NGAL and PCR best predicted severe vs mild to moderate fDGF, with AUCs of 0.74 and 0.76 versus 0.65 for TFS. Therefore, urinary NGAL and FE-NGAL may provide a viable alternative to TcMAG3 renography for monitoring fDGF clearance or guiding kidney transplant biopsy to exclude additional acute rejection.
由于严重的缺血再灌注损伤,心脏死亡后器官捐献(DCD)肾移植受者发生移植肾功能延迟恢复(DGF)的风险很高。我们将尿生物标志物预测DGF持续时间的能力与作为金标准的肾小管功能斜率(TFS)进行了比较。在89例DCD肾移植受者中,通过液相色谱-串联质谱(LC-MS/MS)分析法对术后第1、4和10天的尿基质金属蛋白酶组织抑制因子-2(TIMP-2)、胰岛素样生长因子结合蛋白7(IGFBP7)、β2微球蛋白(B2M)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤分子-1(KIM1)、CXC趋化因子配体9(CXCL9)和尿调节蛋白(UMOD)进行了定量分析。在术后第10天通过方案活检评估间质纤维化和肾小管萎缩(IF/TA)。用锝-巯基乙酰三甘氨酸(Tc-MAG3)肾动态显像计算TFS。通过ROC分析的曲线下面积(AUC)比较预测性能。在所有89例受者中,22%未发生(<7天)、22%轻度(≥7 - 14天)、29%中度(≥14 - <21天)和26%重度(≥21天)的功能性DGF。与无功能性DGF相比,轻度至中度IF/TA存在的比值比(OR)为1.9(95%置信区间:0.4;10.0),重度为15.0(95%置信区间:2.7;84.8)。在术后第4天,尿NGAL和尿NGAL排泄分数(FE-NGAL)在预测功能性DGF方面优于TFS和其他生物标志物,AUC分别为0.97、0.98和0.92。在术后第10天,FE-NGAL和PCR在预测重度与轻度至中度功能性DGF方面表现最佳,AUC分别为0.74和0.76,而TFS为0.65。因此,尿NGAL和FE-NGAL可能为TcMAG3肾动态显像提供一种可行的替代方法,用于监测功能性DGF清除或指导肾移植活检以排除额外的急性排斥反应。