Urinary Neutrophil Gelatinase-Associated Lipocalin: A Useful Biomarker for Tacrolimus-Induced Acute Kidney Injury in Liver Transplant Patients

被引：37

作者：

Tsuchimoto, Ayami ^{[1
]}

Shinke, Haruka ^{[1
]}

Uesugi, Miwa ^{[1
]}

Kikuchi, Mio ^{[1
,2
]}

Hashimoto, Emina ^{[1
]}

Sato, Tomoko ^{[1
]}

Ogura, Yasuhiro ^{[3
]}

Hata, Koichiro ^{[3
]}

Fujimoto, Yasuhiro ^{[3
]}

Kaido, Toshimi ^{[3
]}

Kishimoto, Junji ^{[4
]}

Yanagita, Motoko ^{[5
]}

Matsubara, Kazuo ^{[1
]}

Uemoto, Shinji ^{[3
]}

Masuda, Satohiro ^{[1
]}

机构：

[1] Kyoto Univ Hosp, Dept Clin Pharmacol & Therapeut, Kyoto 606, Japan

[2] Kagawa Univ Hosp, Dept Pharm, Miki, Kagawa, Japan

[3] Kyoto Univ, Grad Sch Med, Dept Surg, Div Hepatobiliary Pancreat Surg & Transplantat, Kyoto, Japan

[4] Kyushu Univ, Fac Med Sci, Dept Res & Dev Next Generat Med, Fukuoka 812, Japan

[5] Kyoto Univ, Grad Sch Med, Dept Nephrol, Kyoto, Japan

来源：

PLOS ONE | 2014年 / 9卷 / 10期

基金：

日本学术振兴会;

关键词：

ACID-BINDING PROTEIN; ACUTE-RENAL-FAILURE; INDUCED NEPHROTOXICITY; RISK-FACTORS; NGAL; EXPRESSION; FIBROSIS; CHILDREN; DISEASE; MARKER;

D O I：

10.1371/journal.pone.0110527

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication of liver transplantation. For early detection of AKI, various urinary biomarkers such as monocyte chemotactic protein-1, liver-type fatty acid-binding protein, interleukin-18, osteopontin, cystatin C, clusterin and neutrophil gelatinase-associated lipocalin (NGAL) have been identified. Here, we attempt to identify urinary biomarkers for the early detection of tacrolimus-induced AKI in liver transplant patients. Urine samples were collected from 31 patients after living-donor liver transplantation (LDLT). Twenty recipients developed tacrolimus-induced AKI. After the initiation of tacrolimus therapy, urine samples were collected on postoperative days 7, 14, and 21. In patients who experienced AKI during postoperative day 21, additional spot urine samples were collected on postoperative days 28, 35, 42, 49, and 58. The 8 healthy volunteers, whose renal and liver functions were normal, were asked to collect their blood and spot urine samples. The urinary levels of NGAL, monocyte chemotactic protein-1 and liver-type fatty acid-binding protein were significantly higher in patients with AKI than in those without, while those of interleukin-18, osteopontin, cystatin C and clusterin did not differ between the 2 groups. The area under the receiver operating characteristics curve of urinary NGAL was 0.876 (95% confidence interval, 0.800-0.951; P<0.0001), which was better than those of the other six urinary biomarkers. In addition, the urinary levels of NGAL at postoperative day 1 (p = 0.0446) and day 7 (p = 0.0006) can be a good predictive marker for tacrolimus-induced AKI within next 6 days, respectively. In conclusion, urinary NGAL is a sensitive biomarker for tacrolimus-induced AKI, and may help predict renal event caused by tacrolimus therapy in liver transplant patients.

引用

页数：10

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