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

• Published in: BMC nephrology Vol. 18; no. 1; p. 10
• Main Authors: Panich, Tanaporn, Chancharoenthana, Wiwat, Somparn, Poorichaya, Issara-Amphorn, Jiraphorn, Hirankarn, Nattiya, Leelahavanichkul, Asada
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07.01.2017; BioMed Central
• Subjects: Activating Transcription Factor 3 - urine; Acute kidney failure; Acute Kidney Injury - diagnosis; Acute Kidney Injury - etiology; Acute Kidney Injury - urine; Adult; Aged; Analysis; Case-Control Studies; Creatinine - blood; Diagnosis; Exosomes - metabolism; Female; Humans; Lipocalin-2 - urine; Male; Middle Aged; Nephrology; Prospective Studies; Risk factors; Sepsis - complications; Sepsis - urine; Transcriptional coactivators; Thailand; Activating transcriptional factor 3; Urine exosome; Biomarker; Neutrophil gelatinase-associated lipocalin; Acute kidney injury
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-016-0415-3

An 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. We 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. The 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, r  = 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. Urine exosome is an interesting source of urine biomarker and uATF3 is an interesting sepsis-AKI biomarker.