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

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

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.

Study Overview

• Status: Completed
• Conditions: Oxidative Stress; Nephropathy
• Intervention / Treatment: Drug: saline; Drug: Glutathione

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.

• Study Type: Interventional
• Enrollment (Actual): 1000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Department of cardiology and nephrology,Huashan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: saline; saline hydration	Drug: saline; NS 500ml intravenously guttae 1-1.5ml/kg per hour,30 minutes before and during coronary angiography
Experimental: Glutathione	Drug: Glutathione; NS 500ml + Glutathione 1.8g intravenously guttae 1-1.5ml/kg per hour,30 minutes before and during coronary angiography; Other Names: brand name:Gluthion; serial numbers:H20040005; manufacturer:Pharminvest SPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	48-72h after coronary angiography

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Investigators: Principal Investigator: Haiming Shi, Professor, Huashan Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: June 8, 2010
• First Submitted That Met QC Criteria: June 10, 2010
• First Posted (Estimate): June 11, 2010

Study Record Updates

• Last Update Posted (Estimate): June 27, 2011
• Last Update Submitted That Met QC Criteria: June 23, 2011
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: contrast medium induced nephropathy; polymorphism of oxidative stress genes; antioxidant prevention
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases
• Other Study ID Numbers: KY2009-296