Surgery-ComplicationsNCT05458063
The Effectiveness of Urine mtDNA and Beta 2-MG to Predict Acute Kidney Injury for Critically Ill Surgical Patients
An observational study of Surgery-Complications and Acute Kidney Injury, run by Wonju Severance Christian Hospital at 1 site in South Korea.
Trial summary
1. Research background 1. Research hypothesis The development of acute kidney injury (AKI) can be predicted using urine mitochondrial deoxyribonucleic acid (UmtDNA), serum and urine beta-2 microglobulin (β2-MG) in critically ill surgical patients 2. Basis of research hypothesis i. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Surgery-Complications, Acute Kidney Injury, Critical Illness
- How many people
- 113 participants
- Where
- 1 siteSouth Korea
- Study dates
- 25 Jul 2022to 10 Jun 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All surgical patients who planned to admit to surgical and trauma intensive care unit in emergency room
Who may be able to join
- All surgical patients who planned to admit to surgical and trauma intensive care unit in emergency room
Who cannot join
- Age ≤18 years
- Pregnancy in women
- Chronic kidney disease history
- Death at initial presentation of the case
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Wonju Severance Christian Hospital
Wŏnju, Gangwon-do, 26426
About this study
Official title: The Effectiveness of the Urine Mitochondrial Deoxyribonucleic Acid and, Serum Beta 2 Microglobulin as a Biomarker of Renal Function Impairment in Critically Ill Surgical Patients
- Research background
- Research hypothesis The development of acute kidney injury (AKI) can be predicted using urine mitochondrial deoxyribonucleic acid (UmtDNA), serum and urine beta-2 microglobulin (β2-MG) in critically ill surgical patients
- Basis of research hypothesis
- Correlation between mitochondria and renal function (Results of previous studies)
- 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.
Read the detailed description
- Research objective
- Demonstrate of the association between urine mitochondrial deoxyribonucleic acid copy number (UmtDNAcn), beta 2-microglobulin (β2-MG) and acute kidney injury in critically ill surgical patients
- Demonstrate of the effectiveness of UmtDNAcn and β2-MG as a biomarker to predict AKI development and recovery
- Contents of the research project.
- Analysis of correlation between UmtDNAcn, β2-MG and development of AKI
- Verifying the correlation between UmtDNAcn and blood β2-MG measured at the initial presentation and patients diagnosed AKI according to the Acute Kidney Injury Network (AKIN) criteria.
- Analysis of correlation between UmtDNAcn, β2-MG and recovery of AKI
- Verifying the correlation between UmtDNAcn and blood β2-MG measured at the initial presentation and AKI recovery
- AKI recovery was defined as 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.
- Comparison with other biomarkers (delta neutrophil index, creatinine, cystatin C) - Comparison of sensitivity and specificity of UmtDNAcn, β2-MG, and other biomarkers previously used such as creatinine, cystatin C, and delta neutrophil index.
- Strategies and methods for the research project
- subject: all surgical patients who planned to admit surgical and trauma intensive care unit in emergency room
- Study period and patient recruitment i. 1st and 2nd year
- 120 patients
- Measurement of UmtDNAcn, β2-MG i. urine and blood sampling: at the initial presentation and again on hospital say #1 and #3
- Analysis of correlation between UmtDNAcn, β2-MG and AKI development, recovery
- Statistical analysis of UmtDNAcn, β2-MG measured at the initial presentation, on hospital day #1, and #3 between patients with no AKI and AKI ii. Statistical analysis of UmtDNAcn, β2-MG measured at the initial presentation, on hospital day #1, and #3 between patients with no AKI recovery and AKI recovery ※ AKI recovery was defined as 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. iii. Comparison with other biomarkers (delta neutrophil index, creatinine, cystatin C)
- Comparison of sensitivity and specificity to predict AKI of UmtDNAcn, β2-MG, and other biomarkers previously used such as creatinine, cystatin C, and delta neutrophil index measure at the initial presentation, on hospital day #1 and #3. .
- Conditions
- Surgery-Complications, Acute Kidney Injury, Critical Illness
- Keywords
- Critically ill surgical patient, Acute kidney injury, Urine mitochondrial DNA, Beta 2-microglobulin, Biomarker
- Medical subject headings
- Acute Kidney Injury, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute kidney injury (dichotomous)
Acute kidney injury according to Acute Kidney Injury Network (AKIN) criteria
Measured: 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
Measured: Within 30 days after ICU admission
Secondary outcomes (3)
Mortality (dichotomous)
The number of deaths
Measured: Within 30 days after ICU admission
Hospital length of stay (continuous)
Measured in days from admission to discharge
Measured: 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)
Measured in days from ICU admission to ICU out
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2022
- Study start25 Jul 2022
- Primary completion10 Jun 2024
- Study completion10 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Surgery-ComplicationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wonju Severance Christian Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Research Foundation of Korea
- Responsible party
- Principal investigator, Kwangmin Kim, Wonju Severance Christian Hospital
- Investigators
- In Sik Shin, Principal investigator, Wonju Severance Christian Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05458063
- Sponsor's protocol ID
- BMPAS2022
- Other IDs
- 2022R1I1A1A01069511
- Status last verified
- Jun 2024
- First submitted
- 11 Jul 2022
- Last updated
- 11 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 18614015Chang 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.
PubMed 31660901Cha 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.
PubMed 32415140Whitaker 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.
PubMed 26287315Hu 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.
PubMed 29682165Trongtrakul 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.
PubMed 29124867
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of the Urine Mitochondrial Deoxyribonucleic Acid and, Serum Beta 2 Microglobulin as a Biomarker of Renal Function Impairment in Critically Ill Surgical Patients
- ClinicalTrials.gov ID
- NCT05458063
- Acronym / sponsor ID
- BMPAS2022
- Conditions
- Surgery-Complications, Acute Kidney Injury, Critical Illness
- Keywords
- Critically ill surgical patient, Acute kidney injury, Urine mitochondrial DNA, Beta 2-microglobulin, Biomarker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Wonju Severance Christian HospitalUniversity, hospital or other
- Collaborators
- National Research Foundation of Korea
- Study start
- 25 Jul 2022 (actual)
- Primary completion
- 10 Jun 2024 (actual)
- Study completion
- 10 Jun 2024 (actual)
- First posted
- 14 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- Research background
- Research hypothesis The development of acute kidney injury (AKI) can be predicted using urine mitochondrial deoxyribonucleic acid (UmtDNA), serum and urine beta-2 microglobulin (β2-MG) in critically ill surgical patients
- Basis of research hypothesis
- Correlation between mitochondria and renal function (Results of previous studies)
- 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.
Detailed description
- Research objective
- Demonstrate of the association between urine mitochondrial deoxyribonucleic acid copy number (UmtDNAcn), beta 2-microglobulin (β2-MG) and acute kidney injury in critically ill surgical patients
- Demonstrate of the effectiveness of UmtDNAcn and β2-MG as a biomarker to predict AKI development and recovery
- Contents of the research project.
- Analysis of correlation between UmtDNAcn, β2-MG and development of AKI
- Verifying the correlation between UmtDNAcn and blood β2-MG measured at the initial presentation and patients diagnosed AKI according to the Acute Kidney Injury Network (AKIN) criteria.
- Analysis of correlation between UmtDNAcn, β2-MG and recovery of AKI
- Verifying the correlation between UmtDNAcn and blood β2-MG measured at the initial presentation and AKI recovery
- AKI recovery was defined as 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.
- Comparison with other biomarkers (delta neutrophil index, creatinine, cystatin C) - Comparison of sensitivity and specificity of UmtDNAcn, β2-MG, and other biomarkers previously used such as creatinine, cystatin C, and delta neutrophil index.
- Strategies and methods for the research project
- subject: all surgical patients who planned to admit surgical and trauma intensive care unit in emergency room
- Study period and patient recruitment i. 1st and 2nd year
- 120 patients
- Measurement of UmtDNAcn, β2-MG i. urine and blood sampling: at the initial presentation and again on hospital say #1 and #3
- Analysis of correlation between UmtDNAcn, β2-MG and AKI development, recovery
- Statistical analysis of UmtDNAcn, β2-MG measured at the initial presentation, on hospital day #1, and #3 between patients with no AKI and AKI ii. Statistical analysis of UmtDNAcn, β2-MG measured at the initial presentation, on hospital day #1, and #3 between patients with no AKI recovery and AKI recovery ※ AKI recovery was defined as 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. iii. Comparison with other biomarkers (delta neutrophil index, creatinine, cystatin C)
- Comparison of sensitivity and specificity to predict AKI of UmtDNAcn, β2-MG, and other biomarkers previously used such as creatinine, cystatin C, and delta neutrophil index measure at the initial presentation, on hospital day #1 and #3. .
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All surgical patients who planned to admit to surgical and trauma intensive care unit in emergency room
Key inclusion criteria (1 listed)
- All surgical patients who planned to admit to surgical and trauma intensive care unit in emergency room
Key exclusion criteria (4 listed)
- Age ≤18 years
- Pregnancy in women
- Chronic kidney disease history
- Death at initial presentation of the case
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Acute kidney injury (dichotomous)
Time frame: Within 30 days after ICU admission
Acute kidney injury according to Acute Kidney Injury Network (AKIN) criteria
Acute kidney injury recovery (dichotomous)
Time frame: Within 30 days after ICU admission
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
3 secondary outcomes
Mortality (dichotomous)
Time frame: Within 30 days after ICU admission
Hospital length of stay (continuous)
Time frame: 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)
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2024.
- Background: PubMed 18614015Pagliarini 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.
- Background: PubMed 31660901Chang 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.
- Background: PubMed 32415140Cha 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.
- Background: PubMed 26287315Whitaker 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.
- Background: PubMed 29682165Hu 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.
- Background: PubMed 29124867Trongtrakul 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
In Sik Shin principal investigator
Wonju Severance Christian Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Surgery-Complications and Acute Kidney Injury, run by Wonju Severance Christian Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute kidney injury (dichotomous) (time frame: Within 30 days after ICU admission). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05458063, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2024.