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中性粒细胞明胶酶相关脂质运载蛋白与延迟应用他克莫司的吗替麦考酚酯联合治疗的肝移植患者中他克莫司诱导的急性肾损伤无关。

Neutrophil Gelatinase-Associated Lipocalin Is Not Associated with Tacrolimus-Induced Acute Kidney Injury in Liver Transplant Patients Who Received Mycophenolate Mofetil with Delayed Introduction of Tacrolimus.

机构信息

Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

出版信息

Int J Mol Sci. 2019 Jun 25;20(12):3103. doi: 10.3390/ijms20123103.

Abstract

Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication. The urinary neutrophil gelatinase-associated lipocalin (NGAL) level has been linked to tacrolimus-induced AKI in patients starting tacrolimus treatment the morning after liver transplantation. Here we tested this association using a different immunosuppression protocol: Mycophenolate mofetil administration beginning on Postoperative Day 1 and tacrolimus administration beginning on Postoperative Day 2 or 3. Urine samples were collected from 26 living donor liver transplant recipients before (Postoperative Day 1) and after (Postoperative Day 7 or 14) tacrolimus administration. NGAL levels were measured via enzyme-linked immunosorbent assays, as were those of three additional urinary biomarkers for kidney diseases: Monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), and human epididymis secretory protein 4 (HE4). HE4 levels after tacrolimus administration were significantly higher in patients who developed AKI ( = 6) than in those who did not ( = 20), whereas NGAL, MCP-1, and L-FABP levels did not differ significantly before or after tacrolimus administration. These findings indicate that NGAL may not be a universal biomarker of AKI in tacrolimus-treated liver transplant recipients. To reduce the likelihood of tacrolimus-induced AKI, our immunosuppression protocol is recommended.

摘要

他克莫司被广泛用作肝移植中的免疫抑制剂,而他克莫司诱导的急性肾损伤(AKI)是一种严重的并发症。尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平与肝移植后开始接受他克莫司治疗的患者的他克莫司诱导的 AKI 有关。在这里,我们使用了不同的免疫抑制方案来检验这种关联:术后第 1 天开始给予霉酚酸酯,术后第 2 或第 3 天开始给予他克莫司。从 26 名活体供肝移植受者中采集了尿液样本,这些样本在开始他克莫司治疗之前(术后第 1 天)和之后(术后第 7 天或第 14 天)进行了收集。通过酶联免疫吸附试验测量了 NGAL 水平,以及另外三个用于肾脏疾病的尿液生物标志物的水平:单核细胞趋化蛋白-1(MCP-1)、肝型脂肪酸结合蛋白(L-FABP)和人附睾分泌蛋白 4(HE4)。在发生 AKI 的患者(n=6)中,他克莫司给药后 HE4 水平明显高于未发生 AKI 的患者(n=20),而 NGAL、MCP-1 和 L-FABP 水平在他克莫司给药前后无显著差异。这些发现表明,NGAL 可能不是接受他克莫司治疗的肝移植受者 AKI 的通用生物标志物。为了降低他克莫司诱导的 AKI 的可能性,我们建议采用这种免疫抑制方案。

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