What is the role of N-acetylcysteine (NAC) in the prevention of acute tubular necrosis (ATN)?

Updated: Mar 15, 2021
  • Author: Sangeeta Mutnuri, MBBS; Chief Editor: Vecihi Batuman, MD, FASN  more...
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The use of N-acetylcysteine (NAC) as a prophylactic agent has gained popularity, on the basis of the theory that contrast media cause direct renal tubular epithelial cell toxicity via exposure to reactive oxygen species (ROS), and NAC is believed to have antioxidant properties that potentially counteract the effects of ROS. [34]  Studies have also suggested that pretreatment with oral NAC (600 mg or 1200 mg bid on the day before and the day of the contrast-requiring procedure) acts as an antioxidant, scavenging ROS and thereby reducing the nephrotoxicity of contrast media.

Based on what is currently known, making a strong, evidence-based recommendation for the use of NAC in the prevention of CIN is not possible. Recognizing that NAC is inexpensive and is not associated with significant complications, in the absence of other effective pharmacologic therapy, its use in clinical practice is not entirely inappropriate. Additional large randomized, controlled trials of NAC are needed to better define its proper role in preventing CIN. The recently published PRESERVE trial demonstrated no benefit of either sodium bicarbonate or NAC for prevention of CIN, compared to saline hydration. [35]

Theophylline, an adenosine antagonist with a similar mechanism of action as NAC, is viewed as another potential agent to prevent CIN, the main difference being the lower risk profile associated with the latter. Its use is based on the idea that contrast media cause local release of adenosine, a known vasoconstrictor considered by some to have a potential role in the pathogenesis of CIN, and theophylline is a known adenosine antagonist. Although theophylline appears to be promising, further randomized trials are required to confirm its benefit in the prevention of CIN.

Aside from the recommended prophylactic medications discussed above, other guidelines recommend withholding potential nephrotoxic agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs).

In patients with underlying volume depletion, withholding ACE inhibitors and/or angiotensin receptor blockers (ARBs) may even be necessary. The use of ACE inhibitors and ARBs is limited by the tendency to cause prerenal failure, especially in patients who are considered to be at high risk; risk factors include advanced age, underlying renovascular disease, concomitant use of diuretics or vasoconstrictors (eg, NSAIDs, COX-2 inhibitors, and calcineurin inhibitors), and elevated baseline serum creatinine.

Metformin should be withheld at least 48 hours before a contrast imaging procedure and if AKI develops.

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