The Effectiveness of Urine mtDNA and Beta 2-MG to Predict Acute Kidney Injury for Critically Ill Surgical Patients

NCT05458063 | Completed

• 2 other identifiers: BMPAS20222022R1I1A1A01069511
• Study Type: observational
• Target: 113
• Locations: 1 country
• Sites: 1

Brief Summary

1\. Research background

• Mitochondria are involved in development and recovery of diabetic nephropathy.
• UmtDNA can be used as early marker to detect the development of AKI ※ Mitochondria
• As an organelle located within the cell, it is an organ that produces energy through adenosine triphosphate (ATP) through cellular oxidative phosphorylation.
• The kidney has the second most mitochondria after the heart. II. Correlation between elevation of β2-MG and renal function
• Circulating β2-MG infiltrates the glomerulus and is reabsorbed and metabolized in the proximal tubule of the kidney. Therefore, it increases in the blood due to a decrease in metabolism when renal function is abnormal. ※ Beta 2-microglobulin
• As the light chain of the class I major histocompatibility antigen, it is a protein distributed in nucleated cells (especially lymphocytes and monocytes) in the body. III. Mechanism of acute kidney injury in critically ill surgical patients
• Blood flow to the kidneys is reduced due to decreased cardiac output, vasoconstriction due to systemic inflammatory response, hemodynamic changes, and decreased body fluid. This leads to renal tubular injury along with ischemic reperfusion injury.
• Renal tubular injury increases the permeability of the transition pore that connects the outer and inner mitochondrial membranes, resulting in mitochondrial structural damage and oxidative injury. It causes a decrease of ATP in kidney cells and induces apoptosis of kidney cells.
• Urine mtDNA, a product of this kidney injury, could be used as a biomarker to predict impairment of renal function in critically ill surgical patients.
• Serum β2-MG maybe increase due to a decrease of metabolism of β2-MG in AKI.

Conditions

Surgery-Complications; Acute Kidney Injury; Critical Illness

Keywords

Critically ill surgical patient; Acute kidney injury; Urine mitochondrial DNA; Beta 2-microglobulin; Biomarker

Outcome Measures

Primary Outcomes (2)

• Acute kidney injury (dichotomous)

  Acute kidney injury according to Acute Kidney Injury Network (AKIN) criteria

  Within 30 days after ICU admission

• Acute kidney injury recovery (dichotomous)

  the case when the AKI stage according to the AKIN criteria on the 7th day of AKI onset was reduced from AKI stage measured at the beginning of the AKI onset

  Within 30 days after ICU admission

Secondary Outcomes (3)

• Mortality (dichotomous)

  Within 30 days after ICU admission

• Hospital length of stay (continuous)

  From date of the admission until the date of first discharge from the hospital, assessed up to 60 days

• Intensive care unit (ICU) stay (continuous)

  From date of ICU admission (in cases of ICU admission at the initial presentation) until the date of first discharge from ICU, assessed up to 60 days

Study Arms (1)

Patients admitted in Surgical intensive care unit and trauma intensive care unit

all surgical patients who planned to admit in surgical and trauma intensive care unit in emergency room

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All surgical patients who planned to admit to surgical and trauma intensive care unit in emergency room

You may qualify if:

• All surgical patients who planned to admit to surgical and trauma intensive care unit in emergency room

You may not qualify if:

• Age ≤18 years
• Pregnancy in women
• Chronic kidney disease history
• Death at initial presentation of the case

Sponsors & Collaborators

• Wonju Severance Christian Hospital: lead
• National Research Foundation of Korea: collaborator

Study Sites (1)

Wonju Severance Christian Hospital

Wŏnju, Gangwon-do, 26426, South Korea

Location

Related Publications (6)

• Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, Walford GA, Sugiana C, Boneh A, Chen WK, Hill DE, Vidal M, Evans JG, Thorburn DR, Carr SA, Mootha VK. A mitochondrial protein compendium elucidates complex I disease biology. Cell. 2008 Jul 11;134(1):112-23. doi: 10.1016/j.cell.2008.06.016.

  PMID: 18614015 BACKGROUND

• Chang CC, Chiu PF, Wu CL, Kuo CL, Huang CS, Liu CS, Huang CH. Urinary cell-free mitochondrial and nuclear deoxyribonucleic acid correlates with the prognosis of chronic kidney diseases. BMC Nephrol. 2019 Oct 28;20(1):391. doi: 10.1186/s12882-019-1549-x.

  PMID: 31660901 BACKGROUND

• Cha SW, Shin IS, Kim DG, Kim SH, Lee JY, Kim JS, Yang JW, Han BG, Choi SO. Effectiveness of serum beta-2 microglobulin as a tool for evaluating donor kidney status for transplantation. Sci Rep. 2020 May 15;10(1):8109. doi: 10.1038/s41598-020-65134-6.

  PMID: 32415140 BACKGROUND

• Whitaker RM, Stallons LJ, Kneff JE, Alge JL, Harmon JL, Rahn JJ, Arthur JM, Beeson CC, Chan SL, Schnellmann RG. Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal dysfunction in acute kidney injury. Kidney Int. 2015 Dec;88(6):1336-1344. doi: 10.1038/ki.2015.240. Epub 2015 Aug 19.

  PMID: 26287315 BACKGROUND

• Hu Q, Ren J, Ren H, Wu J, Wu X, Liu S, Wang G, Gu G, Guo K, Li J. Urinary Mitochondrial DNA Identifies Renal Dysfunction and Mitochondrial Damage in Sepsis-Induced Acute Kidney Injury. Oxid Med Cell Longev. 2018 Feb 26;2018:8074936. doi: 10.1155/2018/8074936. eCollection 2018.

  PMID: 29682165 BACKGROUND

• Trongtrakul K, Sawawiboon C, Wang AY, Chitsomkasem A, Limphunudom P, Kurathong S, Prommool S, Trakarnvanich T, Srisawat N. Acute kidney injury in critically ill surgical patients: Epidemiology, risk factors and outcomes. Nephrology (Carlton). 2019 Jan;24(1):39-46. doi: 10.1111/nep.13192.

  PMID: 29124867 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Cell free mitochondrial DNA in urine is released from renal parenchymal cells, and tubular cells

MeSH Terms

Conditions

Acute Kidney Injury; Critical Illness

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• In Sik Shin

  Wonju Severance Christian Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical assistant professor

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: July 14, 2022
• Study Start: July 25, 2022
• Primary Completion: June 10, 2024
• Study Completion: June 10, 2024
• Last Updated: June 11, 2024

Record last verified: 2024-06

Locations

KR (1)