Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Transplantation. 2019 May;103(5):1014-1023. doi: 10.1097/TP.0000000000002472.
Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP7) have been validated as biomarkers for acute kidney injury. We investigated the performance of both markers in predicting the occurrence and duration of functionally defined delayed graft function (fDGF) in donation after circulatory death (DCD) kidney transplant recipients.
Urine samples of 74 DCD recipients were analyzed. TIMP-2 and IGFBP7 were measured with ELISA on postoperative days 1 to 7, day 10, week 6, and month 6, and values were corrected for osmolality (mOsm). Immunosuppression consisted of anti-CD25 antibody induction and triple maintenance therapy (steroids, mycophenolate mofetil, and calcineurin inhibitor). Statistical analysis included receiver operating characteristic curves and multivariate logistic regression.
Fifty-one (69%) renal transplant recipients had fDGF, of which 14 experienced prolonged fDGF (≥21 days). TIMP-2/mOsm on day-1 and day-10 adequately identified patients with fDGF (area under the curve [AUC], 0.91) and prolonged fDGF (AUC, 0.80), respectively, whereas IGFBP7/mOsm did not (AUC, 0.63 and 0.60). Multivariate analysis on day 1 identified 24-hour urinary creatinine excretion and TIMP-2/mOsm as significant predictors of fDGF (AUC, 0.90, 95% confidence interval, 0.80-0.98). The best predictors of prolonged fDGF on day 10 were 24-hour urinary creatinine excretion, TIMP-2/mOsm, and total warm ischemia time with an AUC of 0.85 (95% confidence interval, 0.72-0.95). Consecutive TIMP-2/mOsm values showed a decrease in TIMP-2/mOsm before an increase in estimated glomerular filtration rate, enabling us to monitor fDGF and predict resolution of fDGF.
Urinary TIMP-2, but not IGFBP7, is a promising biomarker to predict the occurrence and duration of fDGF in DCD kidney transplant recipients.
尿组织抑制剂金属蛋白酶-2（TIMP-2）和胰岛素样生长因子结合蛋白-7（IGFBP7）已被验证为急性肾损伤的生物标志物。我们研究了这两种标志物在预测捐赠者循环死亡（DCD）肾移植受者中功能性定义的延迟肾功能恢复（fDGF）发生和持续时间的表现。
分析了 74 名 DCD 受者的尿样。术后第 1 至 7 天、第 10 天、第 6 周和第 6 个月用 ELISA 法测定 TIMP-2 和 IGFBP7，值经渗透压（mOsm）校正。免疫抑制包括抗 CD25 抗体诱导和三联维持治疗（类固醇、霉酚酸酯和钙调磷酸酶抑制剂）。统计分析包括受试者工作特征曲线和多变量逻辑回归。
51 名（69%）肾移植受者发生 fDGF，其中 14 名发生延长的 fDGF（≥21 天）。TIMP-2/mOsm 在第 1 天和第 10 天可以分别很好地识别出发生 fDGF（曲线下面积[AUC]，0.91）和延长的 fDGF（AUC，0.80）的患者，而 IGFBP7/mOsm 则不能（AUC，0.63 和 0.60）。第 1 天的多变量分析确定 24 小时尿肌酐排泄和 TIMP-2/mOsm 是 fDGF 的显著预测因素（AUC，0.90，95%置信区间，0.80-0.98）。第 10 天延长 fDGF 的最佳预测因素是 24 小时尿肌酐排泄、TIMP-2/mOsm 和总热缺血时间，AUC 为 0.85（95%置信区间，0.72-0.95）。连续的 TIMP-2/mOsm 值显示在估计肾小球滤过率升高之前 TIMP-2/mOsm 值下降，使我们能够监测 fDGF 并预测 fDGF 的缓解。
尿 TIMP-2，但不是 IGFBP7，是预测 DCD 肾移植受者 fDGF 发生和持续时间的有前途的生物标志物。
