miRNA in Septic Acute Kidney Injury

Recruiting

• Conditions: Acute Kidney Injury Due to Sepsis; Acute Kidney Injury; Sepsis

• Registration Number: NCT06498336
• Lead Sponsor: University Hospital Ostrava

Brief Summary

Acute kidney injury is a common and serious complication of sepsis and septic shock, which may be associated with a worse outcome of the patient's condition. The exact pathophysiological mechanism of septic acute kidney injury remains a challenge. One of the possible causes appears to be endothelial dysfunction and mitochondrial damage of renal tubular cells. The aim of this study is to identify specific microRNAs associated with these pathophysiological events in sepsis and septic acute kidney injury. And to establish a new potential diagnostic or therapeutic target for the prevention or treatment of septic acute kidney injury.

Detailed Description

Sepsis is generally characterized as a life-threatening organ dysfunction and dysregulating host reaction to the infection (e.g., bacterial, viral, mycotic (1). Typical pathophysiological processes of sepsis include systemic inflammation, immune suppression, activation of the clotting cascade, and increase of endothelial vascular permeability with subsequent leak of fluids into the interstitial space. One of the most important organ damage due to ongoing sepsis is acute kidney injury (AKI), which is also a predictor of mortality in critically ill patients. The exact pathophysiology of septic AKI remains a challenging and poorly understood mechanism. A decrease of oxygen delivery to the tissues during the septic shock and usually high oxygen consumption of renal tubular cells make them prone to ischemia injury with consequences in tubular cell death. Among potential immune inflammatory response biomarkers in sepsis and septic shock might be promising pentraxin 3 (PTX3), which plays an important role in endothelial dysfunction with several pathogenic pathways' activation. Recently has been shown the positive effect of PTX3 on the inhibition of reactive oxygen species, mitochondrial injury, and apoptosis pathway in AKI (3,4). Another promising urinary or serum biomarker of AKI seems to be uromodulin, which is dynamically regulated in response to sepsis. Serum uromodulin concentrations decrease during septic human AKI development and are associated with increased renal and systemic oxidative damage (5,6,7). MicroRNAs are small non-coding RNAs, that have been reported to be useful biomarkers for AKI development or potential target for AKI treatment. Determination of serum PTX3 and uromodulin concomitantly with specific circulating miRNAs associated with PTX3 and uromodulin-specific signaling pathways in critically ill septic patients could bring new insights to septic AKI pathophysiology and contribute to future development of new preventive or therapeutic options in septic patients.

Study Timeline

• Study Start: 2024-05-02
• Study First Submitted: 2024-06-27
• Status Verified: 2024-07
• Study First Submitted QC: 2024-07-04
• Last Update Submitted: 2024-07-04
• Study First Posted: 2024-07-12
• Last Update Posted: 2024-07-12
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

The study group of patients with sepsis with or without acute kidney injury

• age > 18 years
• newly diagnosed sepsis or septic shock with or without acute kidney injury

Healthy volunteers

• no evidence of infection on clinical or laboratory examination
• age > 18 years
• signed informed consent

Exclusion Criteria

The study group of patients with sepsis with or without acute kidney injury

• age < 18 years
• chronic kidney disease at stage 4 or 5 according to KDIGO recommendations (KDIGO) for chronic kidney disease 2024
• patients on chronic dialysis treatment, or after renal transplantation

Healthy volunteers

• acute or chronic infection
• renal disease

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Determination of serum expression of pentraxin 3 (PTX3) and uromodulin	4 days	To determine the concentration of serum PTX3 and serum uromodulin in critically ill septic patients and their comparison to serum concentrations of creatinine and the acute kidney injury (AKI) stage as well as to the concentrations of procalcitonin (PCT) and interleukin-6 (IL-6) as inflammation markers on day 1 and 4 of study. The serum concentrations of PTX3 and uromodulin in ng/mL will be determined also in healthy volunteers to establish the laboratory reference ranges (values).
Determination of expression and 4 days course investigation of miRNAs	4 days	To determine the expression and 4-day time course investigation of 7 specific circulating miRNAs associated with sepsis and septic acute kidney injury from 352 miRNA targets using a two-tailed Quantitative reverse transcription polymerase chain reaction (RT-qPCR). All selected miRNAs will be determined also in healthy volunteers to establish the laboratory reference ranges (values).
Target genes of miRNAs and their association with endothelial dysfunction and mitochondrial injury in sepsis	4 days	To match the target genes (from miRNA database) of these specifically expressed miRNAs with biochemical pathways associated with serum PTX3 and uromodulin involved in endothelial dysfunction of renal microvasculature, the influence of mitochondrial injury/dysfunction with reactive oxygen species production and activation of cell apoptosis in septic acute kidney injury.

Trial Locations

Locations (2)

University Hospital Ostrava; 🇨🇿 Ostrava, Moravian-Silesian Region, Czechia

University Hospital Olomouc; 🇨🇿 Olomouc, Olomouc Region, Czechia