چکیده (انگلیسی):

Background: Contrast-induced nephropathy is a common complication of contrast administration in patients with
chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or
oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed
knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of
acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the
choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney
disease.
Methods/Design: We designed a 4-part study. We have set up randomised controlled cross-over studies to assess
the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral
acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in
normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group
randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic
kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood
flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and
oxidative balance.
Discussion: Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over
the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced
nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large
randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not
reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of
acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time
randomized controlled trials.