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

Oxidative Stress Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01142024
• Other study ID #: KY2009-296
• Status: Completed
• Phase: N/A
• First received: June 8, 2010
• Last updated: June 23, 2011
• Start date: March 2010
• Est. completion date: March 2011

Study information

• Verified date: December 2009
• Source: Huashan Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Kidney Diseases
• Nephropathy
• Oxidative Stress

Intervention

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

Locations

Country	Name	City	State
China	Department of cardiology and nephrology,Huashan Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Huashan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes