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.

• Klíčová slova
• Acute kidney injury, Gentamicin, Nephrotoxicity, Sepsis, Vancomycin, microRNA,
• MeSH
• akutní poškození ledvin * komplikace   MeSH
• antibakteriální látky terapeutické užití   MeSH
• cirkulující mikroRNA * MeSH
• dospělí MeSH
• gentamiciny MeSH
• interleukin-6 metabolismus   MeSH
• kreatinin MeSH
• lidé MeSH
• lipokalin-2 MeSH
• mikro RNA * genetika   MeSH
• prokalcitonin MeSH
• sepse * komplikace   MeSH
• vankomycin terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• cirkulující mikroRNA * MeSH
• gentamiciny MeSH
• interleukin-6 MeSH
• kreatinin MeSH
• lipokalin-2 MeSH
• mikro RNA * MeSH
• prokalcitonin MeSH
• vankomycin MeSH

Acute kidney injury is a common complication in critically ill patients with sepsis and/or septic shock. Further, some essential antimicrobial treatment drugs are themselves nephrotoxic. For this reason, timely diagnosis and adequate therapeutic management are paramount. Of potential acute kidney injury (AKI) biomarkers, non-protein-coding RNAs are a subject of ongoing research. This review covers the pathophysiology of vancomycin and gentamicin nephrotoxicity in particular, septic AKI and the microRNAs involved in the pathophysiology of both syndromes. PubMED, UptoDate, MEDLINE and Cochrane databases were searched, using the terms: biomarkers, acute kidney injury, antibiotic nephrotoxicity, sepsis, miRNA and nephrotoxicity. A comprehensive review describing pathophysiology and potential biomarkers of septic and toxic acute kidney injury in septic patients was conducted. In addition, five miRNAs: miR-15a-5p, miR-192-5p, miR-155-5p, miR-486-5p and miR-423-5p specific to septic and toxic acute kidney injury in septic patients, treated by nephrotoxic antibiotic agents (vancomycin and gentamicin) were identified. However, while these are at the stage of clinical testing, preclinical and clinical trials are needed before they can be considered useful biomarkers or therapeutic targets of AKI in the context of antibiotic nephrotoxicity or septic injury.

• Klíčová slova
• acute kidney injury, gentamicin, miRNA, nephrotoxicity, sepsis, vancomycin,
• MeSH
• akutní poškození ledvin chemicky indukované   diagnóza   etiologie   patofyziologie   MeSH
• antibakteriální látky škodlivé účinky   terapeutické užití   MeSH
• biologické markery analýza   MeSH
• gentamiciny škodlivé účinky   terapeutické užití   MeSH
• ledviny účinky léků   patofyziologie   MeSH
• lidé MeSH
• mikro RNA analýza   MeSH
• sepse komplikace   diagnóza   farmakoterapie   patofyziologie   MeSH
• vankomycin škodlivé účinky   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH
• biologické markery MeSH
• gentamiciny MeSH
• mikro RNA MeSH
• vankomycin MeSH