N-Acetylcysteine May Lower CIN Risk

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Reductions in albuminuria observed when the drug was administered prior to cardiac catheterization

Administering N-acetylcysteine (NAC) prior to cardiac catheterization may protect patients from contrast-induced nephropathy (CIN), according to a Canadian study.

The finding comes from a sub-analysis of data from a previously published randomized placebo-controlled study that had shown no protective effect in patients with renal dysfunction. That study, by the same researchers, measured kidney function using estimated glomerular filtration rate (GFR) based on serum creatinine.

For their sub-analysis—which focused on 125 of the original 474 participants—the investigators used urinary albumin excretion as a marker for renal function. Their study is the first to use albuminuria to assess the effects of NAC in patients receiving radiolographic contrast as part of a cardiac procedure, they noted. Serum creatinine, they observed, is not a reliable indicator of renal function.

Moreover, they cited a study suggesting that NAC administration itself temporarily reduces serum creatinine, a finding that they say casts doubt on the results of all studies using end points based on measures of serum creatinine as a surrogate marker for kidney damage.

The researchers, led by Adeera Levin, MD, of the University of British Columbia in Vancouver, explained that albuminuria is a direct consequence of renal glomerular and tubular injury and it increases as glomerular function worsens.

Dr. Levin's group restricted their analysis to patients who had urinalyses performed prior to cardiac catheterization and between three and seven days following the procedure. Of the 125 patients, 56 (mean age 71.6 years) received NAC and 69 (mean age 69.5 years) received placebo. The main outcome measure was change in the urine albumin:creatinine ratio (ACR), a reflection of 24-hour urinary albumin excretion. The two groups had similar baseline characteristics.

ACR improved in 10.7% of NAC-treated patients compared with only 4.3% of placebo recipients, according to a report in Nephrology Dialysis Transplantation (2007; published online ahead of print). ACR worsened in 7.1% of the NAC group compared with 21.7% of the placebo arm. These differences between the groups were statistically significant.

In addition, the change in ACR was not associated with change in kidney function as measured by calculated creatinine clearance or GFR. “This may be due to the fact that creatinine measurement is too insensitive to detect minor amounts of damage to the glomeruli or tubular reabsorption capacity,” the authors wrote.

Given the short half-life of NAC, the finding of a reduction in albuminuria in NAC recipients more than three days after catheterization argues against the effect being simply an artifact of NAC, the investigators observed.

If albuminuria truly reflects changes in glomerular permeability or tubular damage, “then this sub-analysis adds credence to the hypothesis that NAC may have an impact on this parameter, and thus may be protective against CIN,” the authors noted.
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