Polymorphism of Oxidative Stress Genes in the Pathogenesis and Antioxidant Prevention of Contrast Induced Nephropathy

NCT ID: NCT01142024

Last Updated: 2011-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2011-03-31

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.

Conditions

Nephropathy; Oxidative Stress

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

saline

saline hydration

Group Type: PLACEBO_COMPARATOR

saline

Intervention Type: DRUG

NS 500ml intravenously guttae 1-1.5ml/kg per hour,30 minutes before and during coronary angiography

Glutathione

Group Type: EXPERIMENTAL

Glutathione

Intervention Type: DRUG

NS 500ml + Glutathione 1.8g intravenously guttae 1-1.5ml/kg per hour,30 minutes before and during coronary angiography

Interventions

Glutathione

NS 500ml + Glutathione 1.8g intravenously guttae 1-1.5ml/kg per hour,30 minutes before and during coronary angiography

Intervention Type: DRUG

saline

NS 500ml intravenously guttae 1-1.5ml/kg per hour,30 minutes before and during coronary angiography

Intervention Type: DRUG

Other Intervention Names

brand name:Gluthion; serial numbers:H20040005; manufacturer:Pharminvest SPA

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Huashan Hospital

OTHER

Sponsor Role: lead

Responsible Party

HMShi,FDing

Principal Investigators

Haiming Shi, Professor

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital

Locations

Department of cardiology and nephrology,Huashan Hospital

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

KY2009-296

Identifier Type: -

Identifier Source: org_study_id