Inexpensive Drug Found Best for Renoprotection from Contrast Agent

By John Gever, Staff Writer, MedPage Today
Published: February 26, 2008

ANN ARBOR, Mich., Feb. 26 -- For patients at a high risk of contrast-induced
kidney failure, an inexpensive and widely available pill is the most
renoprotective agent of all, including hydration, found a meta-analysis
here.

A 25-cent N-acetylcysteine pill appeared to provide the most consistent
protection against nephropathy caused by iodine-based imaging contrast
agents, beating out hydration, theophylline, fenoldopam, iloprost, statins,
dopamine, trimetazidine, bicarbonate, ascorbic acid, furosemide, and
mannitol.

So showed the analysis of 41 randomized trials, reported by Aine M.
Kelly, M.D., and colleagues at the University of Michigan in the Feb. 19
issue of Annals of Internal Medicine. This analysis found that
N-acetylcysteine with IV saline hydration showed the most consistent benefit
in preventing contrast-induced nephropathy, as measured by serum creatinine levels when compared with saline hydration alone.

"This drug, which is quick, convenient, inexpensive, and widely available,
with no major side effects, appears to be the best choice to protect those
whose kidneys are most at risk," said Dr. Kelly. N-acetylcysteine is carried
in most pharmacies and costs about 25 cents for a 500-mg tablet, the
researchers said.

The trials involved a total of 6,379 patients and they all compared various
protective drugs with periprocedural hydration. Most patients in the studies
had chronic renal impairment.

Up to 10% of patients with normal renal function suffer kidney injury after
receiving iodine-containing contrast agents, with even higher rates in
patients with pre-existing kidney dysfunction or other risk factors, Dr.
Kelly and colleagues said. These agents are the third most common cause of
acute renal failure.

Those statistics were derived mainly from an earlier generation of
high-osmolar contrast agents. Saline hydration and the introduction of
iso-osmolar or low-osmolar contrast agents such as iodixanol have reduced
the rate of contrast-induced nephropathy, but not totally abolished it, Dr.
Kelly and colleagues said.

"Thus, protective agents must still be considered for patients with severe
renal impairment who are to receive large volumes of contrast agents," they
wrote.

Most of the studies were in the context of coronary angiography or CT scans
where the contrast agent was delivered intra-arterially.

The meta-analysis identified N-acetylcysteine as showing the best results
across 26 studies. The aggregated relative risk of nephropathy with this
agent was 0.62 (95% CI 0.44 to 0.48).

On the flip side, furosemide turned out to significantly increase risk of
nephropathy (RR 3.27, 95% CI 1.48 to 7.26) on the basis of two studies.

Fenoldopam, mannitol, and a combination including furosemide, dopamine, and mannitol all showed no sign of benefit, with nonsignificant increases in
risk of nephropathy.