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Open Access Study protocol

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

Euan A Sandilands12, Sharon Cameron3, Frances Paterson3, Sam Donaldson3, Lesley Briody3, Jane Crowe3, Julie Donnelly3, Adrian Thompson2, Neil R Johnston2, Ivor Mackenzie4, Neal Uren5, Jane Goddard6, David J Webb2, Ian L Megson4, Nicholas Bateman12 and Michael Eddleston12*

Author Affiliations

1 National Poisons Information Service (Edinburgh), Royal Infirmary of Edinburgh, Edinburgh, UK

2 Clinical Pharmacology Unit, University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh, UK

3 Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh, Edinburgh, UK

4 Free Radical Research Facility, University of the Highlands & Islands, Inverness, UK

5 Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh, UK

6 Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK

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BMC Clinical Pharmacology 2012, 12:3  doi:10.1186/1472-6904-12-3

Published: 3 February 2012

Abstract

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.

Trial registration

Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.

Keywords:
Contrast-induced nephropathy; acetylcysteine; prevention; kidney; contrast media