Acetylcysteine and enzymatic creatinine: beware of laboratory artefact!
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- Lognard, M., Cavalier, E., Chapelle, J. et al. Intensive Care Med (2008) 34: 973. doi:10.1007/s00134-007-0972-9
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Sir: N-Acetylcysteine (NAC) is an antioxidant agent used as a mucolytic and to prevent acute hepatic failure following paracetamol poisoning . NAC has also been thought to prevent radiocontrast nephrotoxicity . Potential analytical interferences between NAC and creatinine measurement have been poorly studied. Tepel et al. showed no interference between their Jaffé creatinine and NAC in vitro . Enzymatic methods are more precise and specific for creatinine measurement than the classic Jaffé methods . Enzymatic assays are thus recommended. However, creatinine enzymatic assays are not free from interference, as has been described with flucytosine and high doses of dobutamine .
We have studied, in vitro, potential interferences between NAC and creatinine measurement by Jaffé and enzymatic methods. We decided to study three serum pools with creatinine concentrations around 1, 2 and 4.5 mg/dl. Each sample was analysed in duplicate before and directly after adding increasing doses of NAC from 500 to 10,000 μg/ml (ampoule at a concentration of 100,000 μg/ml), using both the Jaffé method (CREA Jaffé; Roche Modular, Mannheim, Germany) and the enzymatic method (CREA Plus; Roche Modular, Mannheim, Germany). Volumes of the samples were adjusted to avoid dilution interference. Interference was considered as significant when the difference between the values measured before and after NAC addition was over 10% . We performed the experiment in triplicate. The mean creatinine values of pools were thus 1.01 ± 0.24 mg/dl, 2.14 ± 0.07 mg/dl and 4.83 ± 0.49 mg/dl.
Interference of N-acetylcysteine (NAC) in enzymatic creatinine measurements (expressed in mg/dl)
Concentration of NAC added in vitro (μg/ml)
Three pools around 1 mg/dl (mean: 1.01 mg/dl): mean differences in % from baseline concentrations (standard deviation)
Three pools around 2 mg/dl (mean: 2.14 mg/dl): mean differences in % from baseline concentrations (standard deviation)
Three pools around 4.5 mg/dl (mean: 4.83 mg/dl): mean differences in % from baseline concentrations (standard deviation)
In this study, we show that NAC can interfere with the dosage of creatinine by enzymatic assay and lead to an underestimation of creatinine concentration. The enzymatic technique involves the liberation of hydrogen peroxide, which produces colour by oxidizing a chromogenic dye [3, 5]. As it has powerful antioxidant effect, NAC may thus theoretically interfere with the coloration. However, significant interference occurs only at high NAC concentration (over 1,000 μg/ml), whatever the initial serum creatinine concentration. As NAC is quickly metabolized by the organism (plasma concentration of 20 μg/ml at 2 h after injection of 600 mg), such analytical interference is of clinical importance only in specific circumstances. Even when NAC is administered at very high dosage in the case of paracetamol poisoning, the average plasma NAC concentration is 554 μg/ml after a loading dose of 150 mg/kg . At such plasma concentrations, our in vitro results confirm the absence of significant laboratory artefact of NAC in the enzymatic creatinine measurement. However, if the blood sample is drawn on a multiple-lumen catheter where NAC is perfused and which has not been correctly clamped before sampling, high concentrations of NAC may be present in the sample. In this case, a significant falsely low value of creatinine might be obtained with the enzymatic method, as has been described for dobutamine .