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

BMC Clinical Pharmacology

Michael Eddleston¹  Nicholas Bateman¹  Ian L Megson⁴  David J Webb¹  Jane Goddard⁵  Neal Uren³  Ivor Mackenzie⁴  Neil R Johnston¹  Adrian Thompson¹  Julie Donnelly²  Jane Crowe²  Lesley Briody²  Sam Donaldson²  Frances Paterson²  Sharon Cameron²  Euan A Sandilands¹ 

[1] Clinical Pharmacology Unit, University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh, UK;Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh, Edinburgh, UK;Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh, UK;Free Radical Research Facility, University of the Highlands & Islands, Inverness, UK;Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK

关键词: contrast media;    kidney;    prevention;    acetylcysteine;    Contrast-induced nephropathy;   

Others  :  860802
DOI  :  10.1186/1472-6904-12-3

 received in 2012-01-04, accepted in 2012-02-03,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Sandilands et al; licensee BioMed Central Ltd.

【 图 表 】

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