Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol

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.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.Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.Radiographic contrast material has been used for over 70 years to enhance medical imaging in diagnostic and interventional procedures. While considered generally safe in healthy patients [1,2], it can lead to renal impairment particularly in the presence of co-morbidity [3]. Contrast-induced nephropathy (CIN) is typically defined as an increase in serum creatinine of 25% over baseline, or an absolute increase of 0.5 mg/dL (44.2 μmol/l), within 48 hours of contrast adminis