N-acetylcysteine prevents contrast-induced nephropathy

SEOUL, KOREA. Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired renal failure and associated mortality. Contrast agents (x-ray dyes) are used routinely to “amplify” the x-ray image of the heart and arteries during such procedures as coronary angiography and catheter ablation. Unfortunately, commonly used contrast agents are hard on the kidneys and their use can result in kidney failure in patients who already have impaired kidney function. Several studies have shown that the natural antioxidants N-acetylcysteine (NAC) and ascorbic acid (vitamin C) can reduce the risk of kidney failure in susceptible patients if administered in relatively large doses prior to and subsequent to the procedure.

A group of researchers from the Seoul National University Hospital recently carried out a controlled clinical trial to determine which of the two antioxidants, NAC or ascorbic acid (AA), is the most effective in preventing CIN. Their trial included 212 patients with renal impairment (basal creatinine clearance at or below 60 mL/min and/or serum creatinine level (SCr) of 1.1 mL/dL (100 mmol/L) or higher. The patients were all on statin drugs for elevated cholesterol levels. Over 60% had hypertension, about 40% had diabetes, and almost 50% were current smokers – not a healthy bunch!

The study participants were all scheduled to undergo coronary angiography with the use of the iodine-containing contrast agent iodixanol. They were randomized to receive either 1200 mg of NAC (orally) every 12 hours starting the evening prior to the procedure followed by another two 1200 mg doses (12 hours apart) starting the evening after the procedure, or to receive 3 grams and 2 grams of AA prior to the procedure and 2 grams twice following the procedure with all AA doses being given 12 hours apart. Serum creatinine levels were measured in the morning on the day prior to the angiography procedure and in the morning of days 1 and 2 following.

The researchers found that SCr levels tended to peak on day 2 at which time the average SCr level in the NAC group had decreased by 0.03 mg/dL (2.7 mmol/L) over baseline, while it had increased by 0.04 mg/dL (3.3 mmol/L) in the AA group. The protective effect of NAC was particularly impressive in a subgroup of patients with diabetes. Here NAC decreased SCr by an average of 0.05 mg/dL (4.4 mmol/L) over baseline, while members of the AA group saw an average increase in SCr of 0.09 mg/dL (8 mmol/L).

The incidence of CIN was 1.2% in the NAC group versus 4.4% in the AA group. Again, the protective effect of NAC was particularly impressive among diabetics where 0% experienced CIN as compared to 12.5% who experienced CIN (kidney damage) in the AA group. The Korean researchers conclude that NAC is more effective than ascorbic acid in preventing contrast-induced nephropathy, especially in patients with diabetes.

Jo, SH, et al. N-acetylcysteine versus ascorbic acid for preventing contrast-induced nephropathy in patients with renal insufficiency undergoing coronary angiography. American Heart Journal, Vol. 157, March 2009, pp. 576-83

Editor’s comment: The finding that n-acetylcysteine (NAC) is highly effective in preventing further kidney damage in patients with already impaired kidney function if highly important in its own right. However, the cut-off point of 1.1 mg/dL (100 mmol/L) above which kidney function is considered to be impaired is arbitrary. There is no reason to believe that if NAC protects a person with a SCr of 1.2 mg/dL (106 mmol/L) from kidney damage that it would not also protect a person with an SCr level of 0.9 mg/dL (80 mmol/L) or even lower. Thus, it would seem prudent for all afibbers scheduled to undergo a catheter ablation to ensure that they, along with the appropriate pre-procedure hydration regimen, receive two 1200 mg doses of NAC prior to the procedure (12 hours apart) followed by two 1200 mg doses following the procedure.