Urinary exosomal activating transcriptional factor 3 as the early diagnostic biomarker for sepsis-induced acute kidney injury

BMC Nephrology

Research Article

Wiwat Chancharoenthana¹  Nattiya Hirankarn²  Asada Leelahavanichkul³  Tanaporn Panich⁴  Poorichaya Somparn⁵  Jiraphorn Issara-Amphorn⁵ 

[1] Division of Nephrology, Department of Medicine, Chulalongkorn University, 10330, Bangkok, Thailand;Division of Nephrology and Hypertension, Department of Medicine, Princess Chulabhorn College of Medical Sciences, Chulabhorn Royal Academy of Science (CRAS), 10210, Bangkok, Thailand;Immunology Unit, Department of Microbiology, Chulalongkorn University, 10330, Bangkok, Thailand;Immunology Unit, Department of Microbiology, Chulalongkorn University, 10330, Bangkok, Thailand;Division of Nephrology, Department of Medicine, Chulalongkorn University, 10330, Bangkok, Thailand;Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Chulalongkorn University, 10330, Bangkok, Thailand;Immunology Unit, Department of Microbiology, Chulalongkorn University, 10330, Bangkok, Thailand;Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand;Research Affairs, Faculty of Medicine, Chulalongkorn University, 10330, Bangkok, Thailand;

关键词: Activating transcriptional factor 3;    Acute kidney injury;    Biomarker;    Neutrophil gelatinase-associated lipocalin;    Urine exosome;   

DOI  :  10.1186/s12882-016-0415-3

 received in 2016-08-25, accepted in 2016-12-09,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAn early sepsis-induced acute kidney injury (sepsis-AKI) biomarker is currently in needed. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a candidate of sepsis-AKI biomarker but with different cut-point values. Urinary exosomal activating transcriptional factor 3 (uATF3) has been mentioned as an interesting biomarker.MethodsWe conducted experiments in mice and a prospective, multicenter study in patients as a proof of concept that urine exosome is an interesting biomarker. An early expression of ATF3 in kidney of CD-1 mice at 6 h after cecal ligation and puncture implied the possibility of uATF3 as an early sepsis-AKI biomarker. Increase serum creatinine (Scr) ≥0.3 mg/dL from the baseline was used as an AKI diagnosis and urine was analyzed for uATF3 and uNGAL. Patients with baseline Scr at admission ≥1.5 mg/dL were excluded.ResultsThe analysis showed higher Scr, uNGAL and uATF3 in patients with sepsis-AKI in comparison with patients with sepsis-non-AKI and healthy volunteers. A fair correlation, r2 = 0.47, between uATF3 and uNGAL was showed in sepsis-AKI group with Scr ≥2 mg/dL. To see if uATF3 could be an early sepsis-AKI biomarker, urine sample was collected daily during the first week of the admission. In sepsis-AKI and sepsis-non-AKI groups, uNGAL were 367 ± 43 ng/mL and 183 ± 23 ng/mL, respectively; and uATF3 were 19 ± 4 ng/mL and 1.4 ± 0.8 ng/mL, respectively. With the mean value of uNGAL and uATF3 in sepsis AKI as a cut-off level, AUROC of uNGAL and uATF3 were 64% (95% CI 0.54 to 0.74) and 84% (95% CI 0.77 to 0.91), respectively.ConclusionsUrine exosome is an interesting source of urine biomarker and uATF3 is an interesting sepsis-AKI biomarker.

【 授权许可】

CC BY   
© The Author(s). 2017