Use of Urinary Cell-Cycle Arrest Biomarkers in Contrast-Associated Nephropathy After Coronary Angiography

August 16, 2021 updated by: Eva de Miguel Balsa

Prognostic Value of Urinary TIMP-2/ IGFBP7 in Intra-Arterial Contrast-Associated Acute Kidney Injury

Radiological examinations that require the administration of iodinated contrasts (IC) for diagnostic and therapeutic purposes are essential in current clinical practice, and their use in interventional procedures has been progressively increasing.

IC can cause kidney damage, so there is caution in their use in at-risk populations. This fact may limit its diagnostic use, with data on underutilization of interventional techniques in patients with renal insufficiency, which worsen their prognosis.

In addition, once the use of IC contrasts is decided, preventive measures, such as hyperhydration,are used and can have potential side effects, especially in patients at risk of heart failure (acute coronary syndrome, low left ventricular ejection fraction).

New biomarkers of kidney damage have recently been developed, based on the detection of molecules expressed by the kidney in situations of early damage. The quantitative determination of cell cycle arrest proteins (Tissue Inhibitor of metalloproteinase 2 (TIMP2) and Insulin-Like Growth Factor Binding Protein -7 (IGFBP7)) can be predictive of the development of moderate to severe contrast-associated acute kidney injury.

Urinary determination of [TIMP-2] x [IGFBP7] in patients with ACS (acute coronary syndromes) before cardiac catheterization would allow early identification of those patients vulnerable to IC-induced toxicity and adjustment of preventive measures.

Study Overview

Detailed Description

Urinary determination of [TIMP-2] x [IGFBP7] in patients with ACS undergoing cardiac catheterization would allow early identification of those patients vulnerable to IC-induced toxicity and adjustment of both appropriate preventive measures.

A prospective, descriptive observational study will be carried out to determine sensitivity and specificity of the urinary determination of TIMP2-IGFBP7 and predictive values in the early diagnosis of contrast-associated acute kidney injury (AKI) in patients admitted to the Coronary Care Unit (CCU) in a spanish hospital.

OBJECTIVES

  • PRIMARY OBJECTIVE: To determine the operational characteristics (sensitivity, specificity) of the TIMP2-IGFBP7 biomarker in routine clinical practice, in the early diagnosis of contrast-induced AKI (acute renal injury) in patients admitted to the CCU, exposed to iodinated contrasts. The established renal failure is defined as KDIGO (Kidney Disease Improving Global Outcomes) stage ≥ 2 in the 24 to 72 hours after the administration of contrasts.
  • SECONDARY OBJECTIVES

Evaluate these parameters according to the patient's initial risk level:

  • Estimated renal function upon admission
  • Initial severity estimated by GRACE score
  • Sex
  • Age
  • Contrast media type and volume
  • Patient weight
  • Dose of contrast
  • Diabetes

A single determination (10 ml of fresh urine) should be collected in a sterile container and the laboratory should centrifuge them within the time of collection. Neither the attending physicians nor the investigators will know the results, and the treatment will not be influenced.

The result is reported as a single value which is the concentration of TIMP-2 (ng / mL) multiplied by the concentration of IGFBP7 (ng / mL) divided by 1000. The result is reported without any unit or concentrations of individual biomarkers. As previously reported, a value of> 0.3 identifies patients with a high probability of presenting a moderate to severe AKI (acute kidney injury) in 12 hours, while a value of ≤ 0.3 identifies patients with a low risk of developing a moderate to serious AKI

An aliquot of urine will be stored at -80 ° C in the Clinical Analysis Department

Study Type

Observational

Enrollment (Actual)

194

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alicante
      • Elche, Alicante, Spain, 03203
        • Hospital General Universitario de Elche

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients older than 21 years, with moderate / high risk acute coronary syndrome according to GRACE score and exposed to intra-arterial iodinated contrast media

Description

Inclusion Criteria:

  • Patients older than 21 years exposed to intra-arterial iodinated contrast media for diagnostic / therapeutic purposes and who have signed the Informed Consent document.

Exclusion Criteria:

  • Patients who have been exposed to a previous dose of iodinated contrast within 72 hours prior to recruitment.
  • Patients with urgent radiodiagnostic intervention criteria, when it is not possible to obtain a previous urine sample without delaying the diagnosis and / or the intervention.
  • Patients in anuria.
  • Patients with chronic kidney disease, treated with hemodialysis (HD) or peritoneal dialysis.
  • Bilirubinuria: bilirubin concentrations in the urine> 7.2 g / dL interfere with the result.
  • Patients in terminal situations, in which diagnostic and therapeutic tests are limited.
  • Patients under 21 years.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with ACS undergoing cardiac catheterization

Adults with moderate / high risk acute coronary syndrome undergoing coronary intervention.

The sample will be selected consecutively, including patients admitted to the Cardiac Coronary Unit and who require a radiological test with intra-arterial IC administration, for diagnostic or diagnostic / therapeutic purposes

Urinary determination of TIMP2-IGFBP7 in the an urine sample obtained within 12 hours prior to contrast administration. A single determination will be made, which will be sent to the laboratory. The doctor who treats the patient will not know the result of the test, and the treatment will not be influenced by the result.

According to the manufacturer, 10 ml of fresh urine should be collected in a sterile container and the laboratory should centrifuge them within the time of collection.

The result is reported as a single value calculated as the concentration of TIMP-2 (ng / mL) multiplied by the concentration of IGFBP7 (ng / mL) divided by 1000. The result is reported without units.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Contrast-Associated Acute Kidney Injury
Time Frame: up to 72 hours of exposure
Absolute increase of 0.3 mg / dl in the creatinine value and / or a relative increase greater than 1.5 times the baseline creatinine value, measured at 48 and 72 hours after exposure to contrast.
up to 72 hours of exposure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: up to 30 days
Patients who die during their hospital stay for any reason
up to 30 days
Need of renal replacement techniques
Time Frame: From exposure to contrasts to three months
Hemodialysis, peritoneal dialysis or continuous renal replacement techniques,
From exposure to contrasts to three months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2019

Primary Completion (Actual)

March 30, 2021

Study Completion (Actual)

March 30, 2021

Study Registration Dates

First Submitted

November 10, 2019

First Submitted That Met QC Criteria

November 13, 2019

First Posted (Actual)

November 14, 2019

Study Record Updates

Last Update Posted (Actual)

August 17, 2021

Last Update Submitted That Met QC Criteria

August 16, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GV/2019/003

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Contrast-induced Nephropathy

Clinical Trials on Urinary determination of TIMP-2/ IGFBP7

3
Subscribe