Expression and 7-day time course of circulating microRNAs in septic patients treated with nephrotoxic antibiotic agents

Abstract

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 nonnephrotoxic 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.