Mechanisms for the Effect of Acetylcysteine on Renal Function After Exposure to Radiographic Contrast Material

Detailed Summary

Millions of people receive radiographic contrast material for investigations like CT and coronary angiography. While considered safe in healthy patients, it can cause acute renal impairment. This is termed radiocontrast-induced nephropathy (RCIN) and is generally defined as an increase in serum creatinine over baseline of more than 25% or 0.5 mg/dL (44.2 μmol/l) within 48 hrs. RCIN occurs in less than 2% of patients with normal renal function but is more common in patients with pre-existing renal damage. The pathophysiology of RCIN is unclear. Possible mechanisms involve 1) reduced renal blood flow leading to acute tubular necrosis and 2) direct renal tubular injury by oxygen free radicals. Current prevention strategies focus on increasing renal blood flow and reducing oxidative stress. Patients at risk of RCIN currently receive fluids, a low dose of contrast, and variable and unproven doses of acetylcysteine. The evidence for acetylcysteine administration is unclear. A RCIN consensus working group reported in the American Journal of Cardiology in September 2006 that "N-acetylcysteine is not consistently effective in reducing the risk for contrast-induced nephropathy". The perception of a benefit from acetylcysteine administration that is unproven has disadvantages as some clinicians report giving larger amounts of radio-contrast to patients who have received acetylcysteine since they believe that it prevents RCIN. There is a need to determine how acetylcysteine might prevent RCIN and to identify the appropriate dose and route of administration. Since acetylcysteine is a vasodilator as well as an antioxidant, it may work in two distinct ways, by preventing reduction in renal blood flow (RBF) or contrast-induced oxidative damage. Previous studies have used changes in serum creatinine. In addition to being an insensitive marker of altered renal function, if contrast causes renal vasoconstriction and acetylcysteine vasodilatation, changes in serum creatinine will not be the ideal marker of effect. Finally the optimum dose and route of acetylcysteine administration is unclear, as illustrated by studies using a variety of doses and routes. We propose to study the mechanism of effects of acetylcysteine on healthy and diseased kidneys, both unstressed and stressed by radiocontrast administration. We hypothesise that acetylcysteine may exert a renoprotective effect in RCIN by a renal vasodilatation and/or antioxidant mechanism.

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