1. Urinary exosomal activating transcriptional factor 3 as the early diagnostic biomarker for sepsis-induced acute kidney injury
- Author
-
Wiwat Chancharoenthana, Tanaporn Panich, Poorichaya Somparn, Jiraphorn Issara-Amphorn, Asada Leelahavanichkul, and Nattiya Hirankarn
- Subjects
0301 basic medicine ,Nephrology ,Adult ,Male ,medicine.medical_specialty ,Urine exosome ,Urinary system ,030232 urology & nephrology ,Urine ,urologic and male genital diseases ,Exosomes ,Gastroenterology ,Sepsis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Lipocalin-2 ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Aged ,Kidney ,Creatinine ,Activating Transcription Factor 3 ,Neutrophil gelatinase-associated lipocalin ,business.industry ,Acute kidney injury ,Biomarker ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Activating transcriptional factor 3 ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Case-Control Studies ,Immunology ,Biomarker (medicine) ,Female ,business ,Research Article - Abstract
Background 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. Methods 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. Results 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, 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. Conclusions Urine exosome is an interesting source of urine biomarker and uATF3 is an interesting sepsis-AKI biomarker.
- Published
- 2016