Using Preprocedural Urine NMR(Nuclear Magnetic Resonance) -Based Metabolomics Analysis

Using Preprocedural Urine NMR-Based Metabolomics Analysis to Prediction the Risk of Contrast Induced Nephropathy Following Elective Coronary Angiography

The use of coronary intervention has increased over the last decade. Contrast induced nephropathy (CIN) that develops as a result of procedures using intravenous or intra arterial contrast enhancement, or other diagnostic procedures, has been reported to be the third leading cause of acute renal failure in hospitalized patients. It has been hypothesized that this occurs as a result of direct toxicity, oxidative stress, and ischemic injury. Numerous studies have evaluated the incidence of CIN in patients undergoing angiography. There are limited studies in the acute care setting. Therefore, a tool that could identify early risk factors for CIN would be valuable for patient care.

Metabolomic profiling is the identification of small molecule metabolites that are altered in response to injury. We hypothetize that urine metabolomic profiles may differ in patients before and after contrast administration coronary intervention.We hypothesized that metabolomic profiles will differ between those patients who develop CIN and those who do not after contrast administration. In addition we believe that metabolomics profiles prior to angiography may identify subjects who will go on to develop CIN and are therefore at higher risk.

Study Overview

• Status: Completed
• Conditions: Contrast-induced Nephropathy; Coronary Angiography
• Intervention / Treatment: Procedure: Coronary Angiography

Detailed Description

The specific aim of this pilot study is to determine if metabolomics profiles differ in patients who develop CIN after contrast administration for coronary angiography versus those who do not. Additionally, our goal was to identify specific urinary metabolites that warrant further investigation.This is a pilot study of prospectively identified patients undergoing a coronary intervention with intraarterial contrast during their evaluation. The study was approved by the University of Shahid Beheshti, Medical institutional review boards.

100 number of patients were enrolled. To be eligible for the study, patients had to be >18 years old, undergoing coronary angiography and have at least 1 of the following high risk features for CIN: diabetes, coronary artery disease, congestive heart failure. Past medical history was confirmed by chart review if available, or patient report.

Patients were excluded from the study if they had an estimated glomerular filtration rate <15 mL/min/1.73 m2, a history of organ transplantation, were currently on immunosuppressive medications, were septic or on antibiotic therapy, had a history of or were currently receiving dialysis of any type, had an exposure to iodinated contrast within 3 days prior to the study, or had multiple doses of contrast given.

Patients were managed according to the treating provider recommendations. No intervention was requested as part of this study. There was no institutional standard for mandatory fluid administration or use of N-acetylcysteine prior to elective coronary angiography.All patients received approximately 60 mili Liter of intravenous iodinated contrast material that was administered via computer-controlled automated power injector at 4 mL per second.

data were collected prospectively after patients were identified as fulfilling inclusion and exclusion criteria, and informed consent was obtained. Data collection included , demographics, dietary history, medical history, physical examination, and electrocardiogram findings, as documented by the treating emergency physician. Medical history was confirmed through patient self-report and review of the medical record when available. Medications administered before arrival were also recorded. No additional laboratory tests were mandated as a part of the trial study and the treating physician ordered all tests, except urinary metabolomics analysis, according to their clinical judgment. Urine samples were collected as a midstream sample or via a foley bag prior to angiography and 12 hours post imaging. Samples were aliquoted into 2 mL samples and frozen at -80˚C.

Serum creatinine levels were recorded at presentation, and at 24 and 72 hours. The outcome measure was the presence CIN, which was defined as an increase in serum creatinine level of ≥0.5 mg/dL above baseline within 72 hours after contrast administration.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Nooshin Dalili

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients had to be >18 years old Undergoing elective coronary angiography

Exclusion Criteria:

• estimated glomerular filtration rate <15 mL/min/1.73 m2
• history of organ transplantation
• using immunosuppressive medications
• septic patients or on antibiotic therapy
• a history of receiving dialysis of any type
• an exposure to iodinated contrast within 3 days prior to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Developed Contrast Induced Nephropathy; Coronary Angiography	Procedure: Coronary Angiography; All patients received approximately 60 mL of intra arterial iodinated contrast material that was administered via computer-controlled automated power injector at 4 mL per second.
OTHER: Without CIN; Coronary Angiography	Procedure: Coronary Angiography; All patients received approximately 60 mL of intra arterial iodinated contrast material that was administered via computer-controlled automated power injector at 4 mL per second.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
developing CIN	an increase in serum creatinine level of ≥0.5 mg/dL above baseline within 48 hours after contrast administration	within 48 hours after contrast administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine Metabolomics	Finding differences between urine metabolites profile between patients develop CIN and without CIN	within 48 hours after contrast administration

Collaborators and Investigators

• Sponsor: Shahid Beheshti University of Medical Sciences
• Investigators: Principal Investigator: Dalili, Shahid Beheshti University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2018
• Primary Completion (ACTUAL): September 1, 2018
• Study Completion (ACTUAL): November 1, 2018

Study Registration Dates

• First Submitted: November 4, 2018
• First Submitted That Met QC Criteria: November 4, 2018
• First Posted (ACTUAL): November 6, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 7, 2018
• Last Update Submitted That Met QC Criteria: November 5, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Contrast Induced Nephropathy; Urine Metabolomics
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases
• Other Study ID Numbers: SBMU23567/J

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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