Specific miRNAs in Sepsis and Nephrotoxic Antibiotic Treatment

Differentiation of Acute Kidney Injury in Sepsis and Due to Nephrotoxic Antibiotic Treatment With Vancomycin and Gentamicin Based on Measurements of Specific miRNAs

Critically ill patients are prone to develop acute kidney injury due to sepsis itself and by administration of potentially nephrotoxic antibiotic treatment (vancomycin or gentamicin). Blood-specific miRNA levels associated with renal tubular damage change in patients treated with vancomycin or gentamicin compared to septic patients treated with other antimicrobials.

Sepsis is generally defined as a life-threatening and dysregulated reaction to infection (bacterial, fungal, or viral) leading to systemic inflammation and organ dysfunction including acute kidney injury [1]. Acute kidney injury in critically ill patients is a common and usually serious condition associated with increased patient morbidity and mortality. Critically ill patients are prone to develop acute kidney injury due to sepsis itself and by administration of potentially nephrotoxic antibiotic treatment (vancomycin or aminoglycoside-gentamicin). To prevent nephrotoxicity and avoid subtherapeutic dosing, drug serum concentrations are usually monitored, with adjustment of dose or dosing interval according to the pharmacokinetic model. However, renal tubular injury can occur even if the treatment is optimally set. In the quest for new preventive or therapeutic targets (biomarkers) in septic/nephrotoxic acute renal damage, a current research focus in microRNAs. Based on data from previously published experimental and human studies we identified specific miRNAs associated with biochemical pathways involved in inflammation, organ ischemia, and nephrotoxicity with their exact determination and time-changing detection during the seven days in studied patients. Blood-specific miRNA levels associated with renal tubular damage change in patients treated with vancomycin or gentamicin compared to septic patients treated with other antimicrobials.

Sampling method:

Whole blood samples were taken on the first, fourth, and seventh days of antibiotic treatment. The first 24 samples (8 patients) were extracted in duplicate for screening of the selected miRNAs. Blood samples were collected into 2.5 mL tubes (Vacutainer® PAXgene, PreAnalytiX® GmbH, A Qiagen/BD Company, Switzerland). Concomitant-ly, the blood samples for NGAL determination were collected into 2.6 or 2 mL neutral tubes (S-Monovette® K3 EDTA, 2.6 mL, red, Sartstedt AG & Co. KG, Germany; or Vacuette® K3 EDTA 2 mL, violet, Greiner Bio-One GmbH, Germany). The blood samples for biochemical (renal and inflammatory) parameters (serum creatinine, interleukin-6, procalcitonin, C-reactive protein) were collected concomitantly with other dai-ly routine biochemical parameters (S-Monovette® serum-gel, 4.9 mL, brown, Sartstedt AG & Co. KG, Germany in University Hospital Ostrava; or Vacuette® serum-gel, 5.0 mL, red, Greiner Bio-One GmbH, Germany in University Hospital Olomouc). The serum antibiotic concentrations (vancomycin and gentamicin) were monitored according to standard care in both cooperating hospitals without needing more blood samples for study.

Inclusion Criteria:

- Critically ill adult septic patients with or without acute kidney injury treated by antimicrobial therapy

Exclusion Criteria:

- Patients in the chronic dialysis program, with stage 4 and 5 chronic kidney disease, or concomitantly treated with another potentially severe nephrotoxic medication (cisplatin, colistin) or combination vancomycin/gentamicin.