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

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ClinicalTrials.gov Identifier: NCT01142024
Recruitment Status : Completed
First Posted : June 11, 2010
Last Update Posted : June 27, 2011
Sponsor:
Information provided by:
Huashan Hospital

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.


Condition or disease Intervention/treatment Phase
Nephropathy Oxidative Stress Drug: Glutathione Drug: saline Not Applicable

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  (Clinical Trial)
Actual Enrollment : 1000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
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 Start Date : March 2010
Actual Primary Completion Date : March 2011
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Glutathione

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




Primary Outcome Measures :
  1. Serum creatinine [ Time Frame: 48-72h after coronary angiography ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01142024


Locations
China, Shanghai
Department of cardiology and nephrology,Huashan Hospital
Shanghai, Shanghai, China, 200040
Sponsors and Collaborators
Huashan Hospital
Investigators
Principal Investigator: Haiming Shi, Professor Huashan Hospital

Responsible Party: Department of cardiology and nephrology,Huashan Hospital, HMShi,FDing
ClinicalTrials.gov Identifier: NCT01142024     History of Changes
Other Study ID Numbers: KY2009-296
First Posted: June 11, 2010    Key Record Dates
Last Update Posted: June 27, 2011
Last Verified: December 2009

Keywords provided by Huashan Hospital:
contrast medium induced nephropathy
polymorphism of oxidative stress genes
antioxidant prevention

Additional relevant MeSH terms:
Kidney Diseases
Urologic Diseases
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs