Contrast-induced nephropathy

Contrast-induced nephropathy is defined as either a greater than 25% increase of serum creatinine or an absolute increase in serum creatinine of 0.5 mg/dL^[1] after percutaneous coronary intervention (PCI) using a contrast agent. Despite extensive speculation, the actual occurrence of contrast-induced nephropathy in other patient populations has not been demonstrated in the literature.^[2]

Risk factors

To minimize the risk for contrast-induced nephropathy, various actions can be taken if the patient has predisposing conditions. These have been reviewed in a meta-analysis.^[3] A separate meta-analysis addresses interventions for emergency patients with baseline insufficient kidney function.^[4]

Three factors have been associated with an increased risk of contrast-induced nephropathy: preexisting decreased kidney function (such as creatinine clearance < 60 mL/min [1.00 mL/s] - online calculator), preexisting diabetes mellitus, and reduced intravascular volume.^[5][6]

A clinical prediction rule is available to estimate probability of nephropathy (increase ≥25% and/or ≥0.5 mg/dl in serum creatinine at 48 h):^[7]

Risk Factors:

• Systolic blood pressure <80 mm Hg - 5 points
• Intraarterial balloon pump - 5 points
• Congestive heart failure (Class III-IV or history of pulmonary edema) - 5 points
• Age >75 y - 4 points
• Hematocrit level <39% for men and <35% for women - 3 points
• Diabetes mellitus- 3 points
• Contrast media volume - 1 point for each 100 mL
• Decreased kidney function:
  • Serum creatinine level >1.5 g/dL - 4 points

or

• • Estimated Glomerular filtration rate (online calculator)

• • 2 for 40–60 mL/min/1.73 m2
  • 4 for 20–40 mL/min/1.73 m2
  • 6 for < 20 mL/min/1.73 m2

Scoring:
5 or less points

• Risk of CIN - 7.5
• Risk of Dialysis - 0.04%

6–10 points

• Risk of CIN - 14.0
• Risk of Dialysis - 0.12%

11–16 points

• Risk of CIN - 26.1*
• Risk of Dialysis - 1.09%

>16 points

• Risk of CIN - 57.3
• Risk of Dialysis - 12.8%

Choice of contrast agent

The osmolality of the contrast agent was previously believed to be an important factor in contrast-induced nephropathy. Today it has become increasingly clear that other physicochemical properties play a greater role, such as viscosity. Attention should be paid to use contrast agents of low viscosity. Moreover, sufficient fluids should be supplied to limit fluid viscosity of urine. Modern iodinated contrast agents are non-ionic, the older ionic types caused more adverse effects and are not used much anymore.

Treatment

Methylxanthines

Adenosine antagonists such as the methylxanthines theophylline and aminophylline, may help^[4] although studies have conflicting results.^[8]

N-acetylcysteine

N-acetylcysteine (NAC) 600 mg orally twice a day, on the day before and of the procedure if creatinine clearance is estimated to be less than 60 mL/min [1.00 mL/s]) may reduce nephropathy. Some authors believe the benefit is not overwhelming.^[9] A systematic review by Clinical Evidence concluded that NAC is "likely to be beneficial" but did not recommend a specific dose.^[10]

Ascorbic acid

Ascorbic acid may help according to a systematic review of randomized controlled trials.^[11]

Research

While there are currently no FDA-approved therapies for contrast-induced nephropathy, two therapies are currently being investigated. CorMedix, Inc. is currently in the latter part of phase II clinical trials with approved phase III Special Protocol Assessment for CRMD001 (unique formulation Deferiprone) to prevent contrast-induced acute kidney injury and to slow progression of chronic kidney disease. Dosing trials began in June 2010 in the sixty patient trial.^[12][13]

PLC Medical Systems, Inc. has begun a phase III clinical trial of RenalGuard Therapy to prevent contrast-induced nephropathy.^[14] The therapy utilizes the RenalGuard System, which measures the patient's urine output and infuses an equal volume of normal saline in real-time. The therapy involves connecting the patient to the RenalGuard System, then injecting a small dosage of furosemide to induce high urine rates.^[15] RenalGuard Therapy has already been studied in two Italian studies, both of which found the therapy to be superior to the current standard of care.^[15][16]

References