Why is N-acetylcysteine a controversial prevention method for contrast-induced nephropathy (CIN)?

Updated: Feb 21, 2020
  • Author: Anita Basu, MD, FACP; Chief Editor: Vecihi Batuman, MD, FASN  more...
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A controversy relating to NAC therapy involves the parameter on which its effectiveness is assessed. It was suggested that the beneficial effect of NAC in CIN is related to its ability to lower serum creatinine (SCr) rather than to improve GFR. It was believed that NAC directly reduces SCr by increasing creatinine excretion (tubular secretion), decreasing its production (augments activity of creatine kinase), or interfering with its laboratory measurement, enzymatic or nonenzymatic (Jaffe method).

This was supported by a study that demonstrated a significant decrease in SCr after four doses of 600 mg of oral NAC in healthy volunteers with normal kidney function and no exposure to radiocontrast media. [51] This would cast doubt on the results of at least 13 randomized, controlled trials that showed NAC to be protective in CIN, with SCr used as the endpoint. However, Haase et al compared the effect of NAC on SCr by simultaneously studying its effect on cystatin C and found that NAC did not artifactually lower SCr when measured by the Jaffe method. [52]

The CIN Working Panel concluded that the existing data on NAC therapy in CIN is sufficiently varied to preclude a definite recommendation. [39] The KDIGO guidelines do recommend use of NAC in conjunction with hydration. In clinical practice, NAC therapy remains part of the standard of care; NAC is routinely administered because of its low cost, lack of adverse effects, and potential beneficial effect, as demonstrated by the relative risk reduction of CIN, ranging from 0.37-0.73, as reported in several meta-analyses.

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