Polymorphism of Oxidative Stress Genes in the Pathogenesis and Antioxidant Prevention of Contrast Induced Nephropathy
Primary Purpose
Nephropathy, Oxidative Stress
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Glutathione
saline
Sponsored by
About this trial
This is an interventional prevention trial for Nephropathy focused on measuring contrast medium induced nephropathy, polymorphism of oxidative stress genes, antioxidant prevention
Eligibility Criteria
Inclusion Criteria:
- receiving cardiovascular angiography;
- age 18 to 80 years ;
- signed informed consent.
Exclusion Criteria:
- baseline serum creatinine level > 8 mg / dL (707 μmol / L);
- an increase in serum creatinine of 0.5 mg / dL (44.2 μmol / L) or more in the 24 hours before angiography;
- dialysis;
- multiple myeloma;
- pulmonary edema;
- uncontrolled hypertension;
- emergency cardiac catheterization;
- exposure to radiographic contrast media within the preceding 2 days;
- allergy to radiographic contrast media; pregnancy and breast-feeding women; acceptance of mannitol and other anti-oxidant treatment.
Sites / Locations
- Department of cardiology and nephrology,Huashan Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
saline
Glutathione
Arm Description
saline hydration
Outcomes
Primary Outcome Measures
Serum creatinine
CIN is defined as a relative increase of the serum creatinine by 25% or as an absolute increase of 0.5mg/dl(44.2umol/l) from baseline within 48-72h after contrast exposure.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01142024
Brief Title
Polymorphism of Oxidative Stress Genes in the Pathogenesis and Antioxidant Prevention of Contrast Induced Nephropathy
Official Title
Polymorphism of Oxidative Stress Relative Genes in Contrast Medium Induced Nephropathy:Implications in the Pathogenesis and the Effect of Antioxidant prevention-a Prospective,Randomized,Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
December 2009
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
March 2011 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Huashan Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
With the wide use of contrast agents in clinical diagnosis and treatment, contrast induced nephropathy(CIN) accounts for 1/3 of hospital acquired acute renal failure.The mortality rate of patients with CIN is up to 35%,and about 30% patients with permanent renal dysfunction.Prevention and treatment of this iatrogenic complication and reducing morbidity has become an urgent task to every medical worker.
Now the pathogenesis of CIN is not clear,while the toxicity of renal tubular epithelial cell and the hypoxia of renal medullary is likely to be the main mechanism of CIN.Iodine contrast agent concentrate in the tubular and collecting duct and directly damage cells,leading to tubular cell death;also induce the release of renal vasoconstrictors,such as adenosine, endothelin, causing acute vasoconstriction.Furthermore,oxidative stress and the inflammatory response induced by ischemia may worsen kidney function.
Thus a large number of studies focus on oxidative stress in the pathogenesis of CIN.Recently,some studies have shown that oxidative stress proteins play an important role in acute renal injury(AKI),and have reported that these proteins of different genotypes related to the incidence and prognosis of AKI.
Therefore,the investigators speculate whether some patients have genetic potential of increased oxidative stress,and are more prone to contrast induced nephropathy? At present,there are a great number of researches about preventive measures of CIN.The firstly and widely used therapy is hydration.But it just dilutes iodine contrast medium in renal tubular and collecting duct,increases urine output to prevent the formation of tubular crystals.According to the pathogenesis of CIN,oxidative stress plays an important role in CIN,thereby several antioxidants,such as N-acetyl cysteine or Glutathione are also under study.But results are inconsistent.
As a result,the investigators designed this study to evaluate the oxidative stress in cardiovascular population on the impact of contrast medium nephropathy,and the relationship in antioxidant enzymes with genetic polymorphisms,to find clinical indicators predicting renal dysfunction and guiding individual treatment to prevent its occurrence.
Detailed Description
With the wide use of contrast agents in clinical diagnosis and treatment, contrast induced nephropathy(CIN) accounts for 1/3 of hospital acquired acute renal failure,leading to prolonged hospital stay and increased medical costs.The mortality rate of patients with CIN is up to 35%,and about 30% patients with permanent renal dysfunction.Prevention and treatment of this iatrogenic complication and reducing morbidity has become an urgent task to every medical worker.
Now the pathogenesis of CIN is not clear,while the toxicity of renal tubular epithelial cell and the hypoxia of renal medullary is likely to be the main mechanism of CIN.Iodine contrast agent concentrate in the tubular and collecting duct and directly damage cells,leading to tubular cell death;also induce the release of renal vasoconstrictors,such as adenosine, endothelin, causing acute vasoconstriction.Furthermore,oxidative stress and the inflammatory response induced by ischemia may worsen kidney function.
Thus a large number of studies focus on oxidative stress in the pathogenesis of CIN.Recently,some studies have shown that oxidative stress proteins,such as the NADPH oxidase p22 phox subunits,promote oxidase,antioxidant enzymes catalase,hypoxia inducible factor-1(HIF-1),play an important role in acute renal injury(AKI),and have reported that these proteins of different genotypes related to the incidence and prognosis of AKI,such as the NADPH oxidase subunit p22 phox (position point of +242 T replaced C).
Therefore,the investigators speculate whether some patients have genetic potential of increased oxidative stress,and are more prone to contrast induced nephropathy? At present,there are a great number of researches about preventive measures of CIN.The firstly and widely used therapy is hydration.But it just dilutes iodine contrast medium in renal tubular and collecting duct,increases urine output to prevent the formation of tubular crystals.According to the pathogenesis of CIN,oxidative stress plays an important role in CIN,thereby several antioxidants,such as N-acetyl cysteine (NAC) or Glutathione are also under study.But results are inconsistent.
As a result,the investigators designed this prospective, randomized,controlled study to evaluate the oxidative stress in cardiovascular population on the impact of contrast medium nephropathy,and the relationship in antioxidant enzymes with genetic polymorphisms,to find clinical indicators predicting renal dysfunction and guiding individual treatment to prevent its occurrence.
Inclusion Criteria:
receiving cardiovascular angiography; age 18 to 80 years ; signed informed consent.
Exclusion Criteria:
serum creatinine level greater than 8 mg / dL (707 μmol / L); change in serum creatinine of 0.5 mg / dL (44.2 μmol / L) or more in the 24 hours before randomization; dialysis, multiple myeloma, pulmonary edema, uncontrolled hypertension, emergency cardiac catheterization, exposure to radiographic contrast media within the preceding 2 days, allergy to radiographic contrast media, pregnancy and breast-feeding women, acceptance of mannitol and other anti-oxidant treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephropathy, Oxidative Stress
Keywords
contrast medium induced nephropathy, polymorphism of oxidative stress genes, antioxidant prevention
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
1000 (Actual)
8. Arms, Groups, and Interventions
Arm Title
saline
Arm Type
Placebo Comparator
Arm Description
saline hydration
Arm Title
Glutathione
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Glutathione
Other Intervention Name(s)
brand name:Gluthion, serial numbers:H20040005, manufacturer:Pharminvest SPA
Intervention Description
NS 500ml + Glutathione 1.8g intravenously guttae 1-1.5ml/kg per hour,30 minutes before and during coronary angiography
Intervention Type
Drug
Intervention Name(s)
saline
Intervention Description
NS 500ml intravenously guttae 1-1.5ml/kg per hour,30 minutes before and during coronary angiography
Primary Outcome Measure Information:
Title
Serum creatinine
Description
CIN is defined as a relative increase of the serum creatinine by 25% or as an absolute increase of 0.5mg/dl(44.2umol/l) from baseline within 48-72h after contrast exposure.
Time Frame
48-72h after coronary angiography
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
receiving cardiovascular angiography;
age 18 to 80 years ;
signed informed consent.
Exclusion Criteria:
baseline serum creatinine level > 8 mg / dL (707 μmol / L);
an increase in serum creatinine of 0.5 mg / dL (44.2 μmol / L) or more in the 24 hours before angiography;
dialysis;
multiple myeloma;
pulmonary edema;
uncontrolled hypertension;
emergency cardiac catheterization;
exposure to radiographic contrast media within the preceding 2 days;
allergy to radiographic contrast media; pregnancy and breast-feeding women; acceptance of mannitol and other anti-oxidant treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haiming Shi, Professor
Organizational Affiliation
Huashan Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of cardiology and nephrology,Huashan Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
12. IPD Sharing Statement
Learn more about this trial
Polymorphism of Oxidative Stress Genes in the Pathogenesis and Antioxidant Prevention of Contrast Induced Nephropathy
We'll reach out to this number within 24 hrs