Mechanisms for the Effect of Acetylcysteine on Renal Function After Exposure to Radiographic Contrast Material
Status:
Completed
Trial end date:
2015-01-01
Target enrollment:
Participant gender:
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.