Avoiding falsely low creatinine concentrations measured in patients treated with N-acetylcysteine for acetaminophen...

Circulating creatinine is a biomarker of paramount importance in clinical practice. In cases of acetaminophen (APAP) intoxication, the antidote, N-acetylcysteine (NAC), interferes with commonly used creatininase-peroxidase methods. This study aimed to assess whether creatininase-amperometric methods were affected in this context.

This study includes in vitro interference tests, involving four creatinine assays using NAC-spiked plasma pools and an in vivo retrospective study comparing creatininase-peroxidase and creatininase-amperometric measurements in patients presenting with NAC-treated APAP poisoning.

Creatininase-peroxidase method was impacted by NAC interference in a clinically-significant manner at therapeutic NAC levels (basal value recovery of 80 % and 70 % for 500 and 1000 mg.L^-1 of NAC, respectively), surpassing the desirable Reference Change Value (RCV%). Enzymo-amperometric methods were not impacted. Among patients, a mean bias of -45.2 ± 28.0 % was observed for the peroxidase detection method compared to the amperometric in those who received NAC prior plasma sampling and -2.7 ± 5.4 % in those who did not.

Our findings indicate that enzymo-amperometric creatinine assays remain unaffected by NAC interference due to the absence of the peroxidase step in the analytical process. Therefore, these methods are suitable to prevent spurious hypocreatininemia in APAP intoxicated patients undergoing NAC therapy.