title: Urinary neutrophil gelatinase-associated lipocalin: a useful biomarker for tacrolimus-induced acute kidney injury in liver transplant patients.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Tsuchimoto
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Shinke
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Uesugi
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan; Department of Pharmacy, Kagawa University Hospital, Kagawa, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Emina
authors.initials: E
authors.lastname: Hashimoto
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sato
authors.affiliation: Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogura
authors.affiliation: Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Hata
authors.affiliation: Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Kaido
authors.affiliation: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kishimoto
authors.affiliation: Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Yanagita
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsubara
authors.affiliation: Division of Hepatobiliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D000328:Adult; D015415:Biomarkers / Q000652:urine; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine*; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D007166:Immunosuppressive Agents; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D016559:Tacrolimus