No. Using N-acetylcysteine (NAC) routinely to prevent contrast-induced acute kidney injury is not supported by the evidence at this time.1,2 However, there is evidence to suggest using it for patients at high risk, ie, those with significant baseline renal dysfunction.3,4
INCIDENCE AND IMPACT OF ACUTE KIDNEY INJURY
Intraarterial use of contrast is associated with a higher risk of acute kidney injury than intravenous use. Most studies of NAC for the prevention of contrast-induced acute kidney injury have focused on patients receiving contrast intraarterially. The reported rates of contrast-induced acute kidney injury also vary depending on how acute kidney injury was defined.
Although the incidence is low (1% to 2%) in patients with normal renal function, it can be as high as 25% in patients with renal impairment or a chronic condition such as diabetes or congestive heart failure, or in elderly patients.5
The development of acute kidney injury after percutaneous coronary intervention is associated with a longer hospital stay, a higher cost of care, and higher rates of morbidity and death.6
RATIONALE FOR USING N-ACETYLCYSTEINE
Contrast-induced acute kidney injury is thought to involve vasoconstriction and medullary ischemia mediated by reactive oxygen species.5 As an antioxidant and a scavenger of free radicals, NAC showed early promise in reducing the risk of this complication, but subsequent trials raised doubts about its efficacy. 1,2 In clinical practice, the drug is often used to prevent acute kidney injury because it is easy to give, cheap, and has few side effects. Recently, however, there have been suggestions that giving it intravenously may be associated with adverse effects that include anaphylactoid reactions.7
THE POSITIVE TRIALS
Tepel et al3 performed one of the earliest trials that found that NAC prevented contrast-induced acute kidney injury. The trial included 83 patients with stable chronic kidney disease (mean serum creatinine 2.4 mg/dL) who underwent computed tomography with about 75 mL of a nonionic, low-osmolality contrast agent. Participants were randomized to receive either NAC (600 mg orally twice daily) and 0.45% saline intravenously or placebo and saline. Acute kidney injury was defined as an increase of at least 0.5 mg/dL in the serum creatinine level 48 hours after the contrast dye was given.
The rate of acute kidney injury was significantly lower in the treatment group (2% vs 21%, P = .01). None of the patients who developed acute kidney injury needed hemodialysis.
Shyu et al4 studied 121 patients with chronic kidney disease (mean serum creatinine 2.8 mg/dL) who underwent a coronary procedure. Patients were randomized to receive NAC 400 mg orally twice daily or placebo in addition to 0.45% saline in both groups. Two (3.3%) of the 60 patients in the treated group and 15 (24.6%) of the 61 patients in the control group had an increase in creatinine concentration greater than 0.5 mg/dL at 48 hours (P < .001).
Both of these single-center studies were limited by small sample sizes and very short follow-up. Further, the impact of the drug on important clinical outcomes such as death and progression of chronic kidney disease was not reported.
Marenzi et al8 randomized 354 patients undergoing coronary angioplasty as the primary treatment for acute myocardial infarction to one of three treatment groups:
- NAC in a standard dosage (a 600-mg intravenous bolus before the procedure and then 600 mg orally twice daily for 48 hours afterward)
- NAC in a high dosage (a 1,200-mg intravenous bolus and then 1,200 mg orally twice daily for 48 hours)
The two treatment groups had significantly lower rates of acute kidney injury than the placebo group. In addition, the hospital mortality rate and the rate of a composite end point of death, need for renal replacement therapy, or need for mechanical ventilation were significantly lower in the treated groups. However, the number of events was small, and a beneficial effect on the death rate has not been confirmed by other studies.5