BACKGROUND: Through regulation of signaling pathways, microRNAs (miRNAs) can be involved in sepsis and associated organ dysfunction. The aims of this study were to track the 7-day time course of blood miRNAs in patients with sepsis treated with vancomycin, gentamicin, or a non-nephrotoxic antibiotic and miRNA associations with neutrophil gelatinase-associated lipokalin (NGAL), creatinine, procalcitonin, interleukin-6, and acute kidney injury (AKI) stage. METHODS: Of 46 adult patients, 7 were on vancomycin, 20 on gentamicin, and 19 on another antibiotic. Blood samples were collected on days 1, 4, and 7 of treatment, and miRNAs were identified using quantitative reverse transcription PCR. RESULTS: The results showed no relationship between miRNA levels and biochemical variables on day 1. By day 7 of gentamicin treatment miR-15a-5p provided good discrimination between AKI and non-AKI (area under curve, 0.828). In patients taking vancomycin, miR-155-5p and miR-192-5p positively correlated with creatinine and NGAL values, and miR-192-5p and miR-423-5p positively correlated with procalcitonin and interleukin-6 in patients treated with a non-nephrotoxic antibiotic. In patients together we found positive correlation between miR-155-5p and miR-423-5p and all biochemical markers. CONCLUSION: The results suggest that these four miRNAs may serve as diagnostic or therapeutic tool in sepsis, renal injury and nephrotoxic treatment. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT04991376 . Registered on 27 July 2021.

Department of Anesthesiology and Resuscitation University Hospital Ostrava 70852 Ostrava Czech Republic

Department of Applied Mathematics Faculty of Electrical Engineering and Computer Science VSB Technical University of Ostrava 70800 Ostrava Czech Republic

Department of Epidemiology and Public Health Faculty of Medicine University of Ostrava 70300 Ostrava Czech Republic

Department of Immunodiagnostics BioVendor R and D Laboratory Medicine Corp 621 00 Brno Czech Republic

Department of Internal Medicine 3 Nephrology Rheumatology and Endocrinology Faculty of Medicine and Dentistry Palacky University Olomouc 77900 Olomouc Czech Republic

Department of Internal Medicine 3 Nephrology Rheumatology and Endocrinology University Hospital Olomouc 77900 Olomouc Czech Republic

Department of Internal Medicine and Cardiology University Hospital Ostrava 70852 Ostrava Czech Republic

Department of Laboratory Diagnostics Institute of Clinical Biochemistry and Clinical Pharmacology University Hospital Ostrava 70852 Ostrava Czech Republic

Faculty of Medicine University of Ostrava 70300 Ostrava Czech Republic

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$a Petejova, Nadezda $u Department of Internal Medicine and Cardiology, University Hospital Ostrava, 70852, Ostrava, Czech Republic. petejova@seznam.cz $u Faculty of Medicine, University of Ostrava, 70300, Ostrava, Czech Republic. petejova@seznam.cz $u Department of Internal Medicine III-Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc, 77900, Olomouc, Czech Republic. petejova@seznam.cz

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$a Expression and 7-day time course of circulating microRNAs in septic patients treated with nephrotoxic antibiotic agents / $c N. Petejova, A. Martinek, J. Zadrazil, V. Klementa, L. Pribylova, R. Bris, M. Kanova, R. Sigutova, I. Kacirova, Z. Svagera, E. Bace, D. Stejskal

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$a BACKGROUND: Through regulation of signaling pathways, microRNAs (miRNAs) can be involved in sepsis and associated organ dysfunction. The aims of this study were to track the 7-day time course of blood miRNAs in patients with sepsis treated with vancomycin, gentamicin, or a non-nephrotoxic antibiotic and miRNA associations with neutrophil gelatinase-associated lipokalin (NGAL), creatinine, procalcitonin, interleukin-6, and acute kidney injury (AKI) stage. METHODS: Of 46 adult patients, 7 were on vancomycin, 20 on gentamicin, and 19 on another antibiotic. Blood samples were collected on days 1, 4, and 7 of treatment, and miRNAs were identified using quantitative reverse transcription PCR. RESULTS: The results showed no relationship between miRNA levels and biochemical variables on day 1. By day 7 of gentamicin treatment miR-15a-5p provided good discrimination between AKI and non-AKI (area under curve, 0.828). In patients taking vancomycin, miR-155-5p and miR-192-5p positively correlated with creatinine and NGAL values, and miR-192-5p and miR-423-5p positively correlated with procalcitonin and interleukin-6 in patients treated with a non-nephrotoxic antibiotic. In patients together we found positive correlation between miR-155-5p and miR-423-5p and all biochemical markers. CONCLUSION: The results suggest that these four miRNAs may serve as diagnostic or therapeutic tool in sepsis, renal injury and nephrotoxic treatment. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT04991376 . Registered on 27 July 2021.

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