Aging Biomakers and ConTrast Induced Nephropathy (ACTIN) Trial (ACTIN)

Biomarkers such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) have been used for the early diagnosis of AKI, although with no definitive results. The investigators explored the association between plasma aging biomakers such as sklotho and contrast induced nephropathy in patients undergoing percutaneous coronary intervention (PCI) with contrast injection.

Study Overview

• Status: Completed
• Conditions: Contrast Induced Nephropathy
• Intervention / Treatment: Drug: contrast

Detailed Description

Acute kidney injury represents an important clinical problem in hospitalized patients, with persistently high rates of mortality and morbidity. With an ever-increasing number of patients receiving intravascular injection of iodinated contrast media worldwide, contrast induced nephropathy (CIN) has become the third leading cause of hospital-acquired AKI. Approximately half of these cases are in patients undergoing cardiac catheterization procedures.

The prevention and early intervention of CIN has been hampered mainly by the lack of a consensus definition and the paucity of early predictive biomarkers to accurately identify high-risk patients. CIN is most frequently defined as an increase in serum creatinine (sCr) by 25-50% above the baseline, generally occurring within the first 24 h after contrast exposure, in the absence of other causes. However, sCr is an unreliable indicator during acute changes in kidney function, and alterations in sCr levels are not particularly sensitive or specific for small changes in the glomerular filtration rate (GFR)e, gender, race and intravascular volume. Biomarkers such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) have been used for the early diagnosis of AKI, although with no definitive results.

• Study Type: Observational
• Enrollment (Actual): 592

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Xiaodong Zhaung

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 18 years or older undergoing planed PCI at the institution of first affiliated hospital of SYSU were prospectively recruited between May 2014 and July 2015. The exclusion criteria were pregnancy, lactation, sepsis, the intravascular administration of a contrast medium within the past 7 days, nephroprotective drug treatment (e.g., N-acetylcysteine, theophylline, sodium bicarbonate, prostaglandin E1), nephrotoxic drug intake (e.g., non-steroidal anti-inflammatory drugs, metformin, aminoglycosides, cisplatin) within the past 7 days, a history of serious allergic to contrast media, renal transplantation, end-stage renal disease necessitating dialysis, and severe concomitant disease of other systems.

Description

Inclusion Criteria:

• Patients aged 18 years or older undergoing planed PCI were prospectively recruited

Exclusion Criteria:

• Pregnancy
• Lactation
• Sepsis
• The intravascular administration of a contrast medium within the past 7 days, nephroprotective drug treatment (e.g., N-acetylcysteine, theophylline, sodium bicarbonate, prostaglandin E1)
• Nephrotoxic drug intake (e.g., non-steroidal anti-inflammatory drugs, metformin, aminoglycosides, cisplatin) within the past 7 days
• A history of serious allergic to contrast media
• Renal transplantation
• End-stage renal disease necessitating dialysis
• Severe concomitant disease of other systems.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CIN proup; The occurrence of CIN was defined as an increase in serum creatinine of 0.5 mg/dL above the baseline value within 48-72 h after PCI. Follow-up SCr and BUN levels were measured 1, 2, and 3 days after the procedure.	Drug: contrast; a substance used to enhance the contrast of structures or fluids within the body in medical imaging. It is commonly used to enhance the visibility of blood vessels and the gastrointestinal tract; Other Names: low-osmolar, non-ionic contrast medium
control group; The occurrence of CIN was defined as an increase in serum creatinine of 0.5 mg/dL above the baseline value within 48-72 h after PCI. Follow-up SCr and BUN levels were measured 1, 2, and 3 days after the procedure.	Drug: contrast; a substance used to enhance the contrast of structures or fluids within the body in medical imaging. It is commonly used to enhance the visibility of blood vessels and the gastrointestinal tract; Other Names: low-osmolar, non-ionic contrast medium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between plasma aging biomakers and contrast induced nephropathy	The plasma concentrations human soluble a-Klotho levels were measured by Enzyme Linked Immunosorbent Assay (ELISA) (Immuno-Biologic Laboratories Co., Ltd. Japan). This novel method detects sklotho using a monoclonal antibody with high affinity to the human a-Klotho protein.Hs-CRP was tested with a Beckman Coulter Immage immunobiochemistry system (USA) using nephelometry (unit: mg/L). Creatinine clearance (CrCl) was calculated by applying the Cockcroft- Gault formula to the serum creatinine concentration.	48-72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between plasma aging biomakers and in-hospital MACE in patients undergoing percutaneous coronary intervention (PCI) with contrast injection.	In-hospital major adverse cardiovascular events (MACE):defined as (1) death, (2) nonfatal myocardial infarction, or (3) target vessel revascularization. Myocardial infarction was diagnosed by a rise in the creatine kinase level to more than twice the upper normal limit with an increased creatine kinase-MB. Target lesion revascularization was defined as a repeat intervention (surgical or percutaneous) to treat a luminal stenosis within the stent or in the 5-mm distal or proximal segments adjacent to the stent. Target vessel revascularization was defined as a reintervention driven by any lesion located in the same epicardial vessel. Thrombotic stent occlusion was angiographically documented as a complete occlusion (TIMI flow 0 or 1) or a flow-limiting thrombus (TIMI flow 1 or 2) of a previously successfully treated artery.	30 days, 1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: zhimin du, MD, fitst affiliated hospital of SYSU

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: January 3, 2016
• First Submitted That Met QC Criteria: January 6, 2016
• First Posted (Estimate): January 8, 2016

Study Record Updates

• Last Update Posted (Estimate): January 8, 2016
• Last Update Submitted That Met QC Criteria: January 6, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases
• Other Study ID Numbers: ACTIN-sysu

Plan for Individual participant data (IPD)

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