N-Acetylcysteine Molecule. Source: www.ganfyd.org

N-acetylcysteine is more renoprotective than hydration alone, and theophylline may reduce the risk for contrast-induced nephropathy, according to a new meta-analysis in the Feb. 18 issue of the Annals of Internal Medicine.

Clinicians use a variety of contrast agents to reduce the risk for contrast-induced nephropathy, including N-acetylcysteine, theophylline, fenoldopam, dopamine, furosemide, mannitol and bicarbonate.

Aine M. Kelly, MD, of the department of radiology, division of cardiothoracic at the University of Michigan and Veteran Affairs Ann Arbor Healthcare System in Ann Arbor, Mich., and colleagues set out to determine the effect of the agents on preventing nephropathy.

The researchers identified the relevant randomized, controlled trials by computerized searches in MEDLINE (1966 to Nov. 3, 2006), EMBASE (1980 to November 2006), PubMed, Web of Knowledge (Current Contents Connect, Web of Science, BIOSIS Previews and ISI Proceedings for the latest five years) and the Cochrane Library databases (up to November 2006).

The investigators selected randomized, controlled trials that administered N-acetylcysteine, theophylline, fenoldopam, dopamine, iloprost, statin, furosemide or mannitol to a treatment group; used intravenous iodinated contrast; defined contrast-induced nephropathy explicitly; and reported sufficient data to construct a 2 x 2 table of the primary effect measure.

In the 41 studies included, N-acetylcysteine (relative risk, 0.62) and theophylline (relative risk, 0.49) reduced the risk for contrast-induced nephropathy more than saline alone, whereas furosemide increased it (relative risk, 3.27), the authors wrote.

The remaining agents did not significantly affect risk, and significant subgroup heterogeneity was present only for N-acetylcysteine, according to the researchers.

“Millions of people receive contrast agent each year, including most heart patients who have angioplasties and stents, as well as those having a CT scan. Contrast agent helps physicians see the things we need to see, but it also does pose a hazard to some people,” Kelly said. “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.”

The limitations of the trial were that all trials evaluated the surrogate end point of contrast-induced nephropathy as the primary outcome; and the lack of a statistically significant renoprotective effect of theophylline may result from insufficient data or study heterogeneity, the authors wrote. They also cautioned that available studies examined laboratory end points (such as an increase in serum creatinine levels) rather than clinical end points (such as dialysis or death).

Kelly and colleagues found that theophylline may also reduce risk for contrast-induced nephropathy, although the detected association was not significant. They concluded that their data support the administration of N-acetylcysteine prophylaxis, particularly in high-risk patients, given its low cost, availability and few side effects.