Biomarkers of Acute Kidney Injury Following Cardiac Surgery

Biomarkers of Acute Kidney Injury Following Cardiopulmonary Bypass Surgery-supported Cardiac Surgery

Acute kidney injury occurs in up to 30% of patients undergoing cardiac surgery. Cardiac surgery associated-acute kidney injury (CSA-AKI) is characterized by a sudden and sustained decrease in renal function with insufficient elimination waste products. The problem is that postoperative diagnosis of CSA-AKI is delayed because it relies solely upon the slow and unreliable rise in serum creatinine (SCr) levels that may lead to delayed start in treatment and increased risk of adverse outcomes. We hypothesize that Matrix Metalloproteins (MMPs) -2, -9 and Neutrophil gelatinase-associated lipocalin (NGAL) are associated with and earlier detectors of CSA-AKI compared to levels of SCr.

Study Overview

• Status: Unknown
• Conditions: Novel Biomarkers of Acute Kidney Injury Following Cardiac Surgery

Detailed Description

Cardiopulmonary bypass (CPB), although essential to the performance of most cardiac operations, has been shown to cause injury to other organs, particularly to the kidneys and brain. Matrix Metalloproteins (MMPs) are ubiquitous proteolytic enzymes that degrade extracellular matrix and have been shown to be involved in injury to transplant kidneys. To date, no interventions are available to decrease the risk of cardiac surgery associated-acute kidney injury (CSA-AKI).

NGAL is a known indicator of injury to kidney, thus making it a promising biomarker for CSA-AKI. It may be that a single biomarker will not be sensitive and specific across the spectrum of CSA-AKI. This research investigates MMP-2, -9 and Neutrophil gelatinase-associated lipocalin (NGAL) and their association with and earlier detection of CSA-AKI compared to levels of SCr.

We hypothesize that increased activity of MMPs are associated with CSA-AKI. Furthermore, MMP-2 and/ or -9 may be predictors and/ or biomarkers for the early detection of CSA-AKI compared to serum levels of creatinine.

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Erick D McNair, PhD; Phone Number: 306 966-7637; Email: erick.mcnair@usask.ca
• Study Contact Backup: Name: Mike Moser, MD; Phone Number: 306 655-5320; Email: mike.moser@usask.ca

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Recruiting
      • University of Saskatchewan
      • Contact: Erick D McNair, PhD; Phone Number: 306 966-7637; Email: erick.mcnair@usask.ca
      • Contact: Mike Moser, MD; Phone Number: 306 655-5320; Email: mike.moser@usask.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Approached as a prospective study male and female patients undergoing cardiopulmonary bypass-supported cardiac surgery were recruited and signed a written consent agreeing to participate in this research.

Description

Inclusion Criteria:

• The inclusion criteria consisted of both sexes, 18-85 years of age, undergoing elective or urgent cardiac surgery with a hemoglobin (Hgb) >100 g/L.

Exclusion Criteria:

• The exclusion criteria included were patients for emergent surgery, pre-existing chronic kidney disease (eGFR<30 mL/min) on dialysis or prescribed nephrotoxic mediations.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
CSA-AKI; Patients that developed cardiac surgery-associated Acute Kidney Injury
non CSA-AKI; Patients that did not developed cardiac surgery-associated Acute Kidney Injury

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increased MMP-2 and -9 in patients that develop CSA-AKI	Increased MMP-2 and -9 activity in serum and or urine in patients that develop CSA-AKI	Pre-CPB, 10 min post-CPB time point, 4 hours post-CPD

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increased NGAL levels in patients that develop CSA-AKI	Increased NGAL levels in serum and or urine in patients that develop CSA-AKI	Pre-CPB, 10 min post-CPB time point, 4 hours post-CPD

Collaborators and Investigators

• Sponsor: University of Saskatchewan
• Investigators: Principal Investigator: Erick D McNair, PhD, University of Saskatchewan

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2020
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): February 1, 2022

Study Registration Dates

• First Submitted: May 8, 2020
• First Submitted That Met QC Criteria: May 8, 2020
• First Posted (Actual): May 13, 2020

Study Record Updates

• Last Update Posted (Actual): May 13, 2020
• Last Update Submitted That Met QC Criteria: May 8, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: Bio 113

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No