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

Contrast-induced Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04163250
• Other study ID #: GV/2019/003
• Status: Completed
• Start date: June 1, 2019
• Est. completion date: March 30, 2021

Study information

• Verified date: August 2021
• Source: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: March 30, 2021
• Est. primary completion date: March 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Contrast-induced Nephropathy
• Kidney Diseases

Intervention

Diagnostic Test:
• Urinary determination of TIMP-2/ IGFBP7
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.

Locations

Country	Name	City	State
Spain	Hospital General Universitario de Elche	Elche	Alicante

Sponsors (1)

Lead Sponsor	Collaborator
Eva de Miguel Balsa

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Contrast-Associated Acute Kidney Injury	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	Mortality	Patients who die during their hospital stay for any reason	up to 30 days
Secondary	Need of renal replacement techniques	Hemodialysis, peritoneal dialysis or continuous renal replacement techniques,	From exposure to contrasts to three months