miRNA in Septic Acute Kidney Injury

NCT06498336 | Completed

• 2 other identifiers: INT-01-sepsis-miRNARVO-FNOs/2024
• Study Type: observational
• Target: 211
• Locations: 1 country
• Sites: 2

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.

Conditions

Sepsis; Acute Kidney Injury; Acute Kidney Injury Due to Sepsis

Keywords

acute kidney injury; endothelial dysfunction; mitochondrial damage; Pentraxin 3; miRNA; sepsis; uromodulin

Outcome Measures

Primary Outcomes (3)

• Determination of serum expression of pentraxin 3 (PTX3) and uromodulin

  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).

  4 days

• Determination of expression and 4 days course investigation of miRNAs

  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).

  4 days

• Target genes of miRNAs and their association with endothelial dysfunction and mitochondrial injury in sepsis

  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.

  4 days

Study Arms (3)

Critically ill adult septic patients without acute kidney injury

The patients in this group will be screened clinically and by standard laboratory biochemical methods to determine sepsis diagnosis according to SEPSIS 3 (1). Blood samples for obtaining serum/plasma of the patients will be taken on the 1st and 4th day of sepsis diagnosis.

Diagnostic Test: Laboratory examination to determine the presence of sepsis

Critically ill adult septic patients with acute kidney injury

The patients will be screened clinically and by standard laboratory biochemical methods to determine sepsis diagnosis according to SEPSIS 3 and acute kidney injury according to KDIGO 2012 (2). Blood samples for obtaining serum/plasma of the patients will be taken on the 1st and 4th day of sepsis diagnosis.

Diagnostic Test: Laboratory examination to determine the presence of sepsis and acute kidney injury

Healthy volunteers

The blood samples for miRNA and biochemical parameters will be collected once, after randomization.

Diagnostic Test: Laboratory examination to determine miRNA and biochemical parameters

Interventions

Laboratory examination to determine the presence of sepsis DIAGNOSTIC_TEST

Standard laboratory biochemical methods will be used to determine sepsis diagnosis accord-ing to SEPSIS 3 (1). Blood samples for obtaining serum/plasma of the patients will be taken on the 1st and 4th day of sepsis diagnosis.

Critically ill adult septic patients without acute kidney injury

Laboratory examination to determine the presence of sepsis and acute kidney injury DIAGNOSTIC_TEST

Standard laboratory biochemical methods will be used to determine sepsis diagnosis according to SEPSIS 3 and acute kidney injury according to Guidelines Kidney Disease Improving Global Outcomes (KDIGO) 2012 (2). Blood samples for obtaining serum/plasma of the patients will be taken on the 1st and 4th day of sepsis diagnosis.

Critically ill adult septic patients with acute kidney injury

Laboratory examination to determine miRNA and biochemical parameters DIAGNOSTIC_TEST

Laboratory examination will be performed to determine miRNA and biochemical parameters.

Healthy volunteers

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Critically ill adult patients suffering from sepsis defined according to SEPSIS 3 definition, with or without acute kidney injury defined by KDIGO 2012 (2) and healthy volunteers

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Ostrava: lead
• University Hospital Olomouc: collaborator

Study Sites (2)

University Hospital Ostrava

Ostrava, Moravian-Silesian Region, 708 52, Czechia

Location

University Hospital Olomouc

Olomouc, Olomouc Region, 779 00, Czechia

Location

Related Publications (7)

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 BACKGROUND

• Chen J, Matzuk MM, Zhou XJ, Lu CY. Endothelial pentraxin 3 contributes to murine ischemic acute kidney injury. Kidney Int. 2012 Dec;82(11):1195-207. doi: 10.1038/ki.2012.268. Epub 2012 Aug 15.

  PMID: 22895517 BACKGROUND

• Lee HH, Kim SY, Na JC, Yoon YE, Han WK. Exogenous pentraxin-3 inhibits the reactive oxygen species-mitochondrial and apoptosis pathway in acute kidney injury. PLoS One. 2018 Apr 19;13(4):e0195758. doi: 10.1371/journal.pone.0195758. eCollection 2018.

  PMID: 29672566 BACKGROUND

• El-Achkar TM, Wu XR, Rauchman M, McCracken R, Kiefer S, Dagher PC. Tamm-Horsfall protein protects the kidney from ischemic injury by decreasing inflammation and altering TLR4 expression. Am J Physiol Renal Physiol. 2008 Aug;295(2):F534-44. doi: 10.1152/ajprenal.00083.2008. Epub 2008 May 21.

  PMID: 18495803 BACKGROUND

• LaFavers KA, Hage CA, Gaur V, Micanovic R, Hato T, Khan S, Winfree S, Doshi S, Moorthi RN, Twigg H, Wu XR, Dagher PC, Srour EF, El-Achkar TM. The kidney protects against sepsis by producing systemic uromodulin. Am J Physiol Renal Physiol. 2022 Aug 1;323(2):F212-F226. doi: 10.1152/ajprenal.00146.2022. Epub 2022 Jun 27.

  PMID: 35759740 BACKGROUND

• LaFavers KA, Macedo E, Garimella PS, Lima C, Khan S, Myslinski J, McClintick J, Witzmann FA, Winfree S, Phillips CL, Hato T, Dagher PC, Wu XR, El-Achkar TM, Micanovic R. Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel. Sci Transl Med. 2019 Oct 2;11(512):eaaw3639. doi: 10.1126/scitranslmed.aaw3639.

  PMID: 31578243 BACKGROUND

• Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024 Apr;105(4S):S117-S314. doi: 10.1016/j.kint.2023.10.018. No abstract available.

  PMID: 38490803 BACKGROUND

Related Links

• 2\. Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1-138.

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood samples

MeSH Terms

Conditions

Sepsis; Acute Kidney Injury

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Naděžda Petejová, Assoc.Prof.,MD,PhD,MSc

  University Hospital Ostrava

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2024
• First Posted: July 12, 2024
• Study Start: May 2, 2024
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: June 3, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (2)