Polymorphism of Oxidative Stress Genes in the Pathogenesis and Antioxidant Prevention of Contrast Induced Nephropathy
Condition: Nephropathy; Oxidative Stress
MeSH terms: Kidney Diseases
Study type: Interventional

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.
    

Intervention name(s): Glutathione; saline
Intervention type(s): Drug; Drug
Intervention description(s): NS 500ml + Glutathione 1.8g intravenously guttae 1-1.5ml/kg per hour,30 minutes before and during coronary angiography; NS 500ml intravenously guttae 1-1.5ml/kg per hour,30 minutes before and during coronary angiography
Other intervention name(s): brand name:Gluthion; serial numbers:H20040005; manufacturer:Pharminvest SPA
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: contrast medium induced nephropathy; polymorphism of oxidative stress genes; antioxidant prevention