Of Hypes and Hopes: N-Acetylcysteine and Cystatin C

doi:10.2214/AJR.07.3210

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Of Hypes and Hopes: N-Acetylcysteine and Cystatin C

Marcus J. Schultz, Annick A. N. M. Royakkers and Catherine S. C. Bouman

Academic Medical Center, University of Amsterdam Amsterdam, The Netherlands
Tergooi Hospitals Blaricum, The Netherlands
Academic Medical Center, University of Amsterdam Amsterdam, The Netherlands

WEB—This is a Web exclusive article.

There are several gold-standard methods for determining glomerular filtrationrate (GFR), including the inulin clearance and radionuclide clearancetechniques. Unfortunately, these techniques are expensive and laboriousand therefore not routinely used in clinical practice. Systemic creatinineconcentrations and clearance of creatinine on the basis of 24-hour urinecollections are frequently used alternative indicators of GFR.However, systemic creatinine concentrations are affected bymuscle mass [1] and diet [2] and vary with age and sex [3].Of importance, as systemic creatinine concentrations rise, tubularsecretion increases, leading to overestimation of GFR in patientswith moderate to severe decreases in renal function [4]. Moreaccurate and practical indicators, preferably an endogenousmarker of GFR, are needed.

In the AJR, Poletti et al. [5] studied the effect of IV administrationof N-acetylcysteine (NAC) on systemic creatinine and cystatinC concentrations in patients with renal insufficiency who underwent emergencycontrast-enhanced CT. Patients were randomized to two groups.In the first group, in addition to hydration, patients receivedNAC. Patients in the second group received hydration only. A25% or greater increase in systemic creatinine concentrationwas found in nine of 43 patients in the control group and intwo of 44 patients in the NAC group (p = 0.026). However, a 25%or greater increase in systemic cystatin C concentration wasfound in nine of 40 patients in the control group and in sevenof 41 patients in the NAC group (p = 0.59). The authors correctlyconclude that although NAC appears protective against contrast-inducednephrotoxicity when using systemic creatinine concentrationsto assess renal function, no effect is found when serum cystatinC concentrations are used.

The authors deserve compliments for their efforts. This studyextends a previous study by Hoffmann et al. [6]. In this study,volunteers with normal renal function who did not receive contrastmedium received NAC. Surrogate markers of renal function, includingsystemic creatinine and cystatin C concentrations were measuredimmediately before and 4 and 48 hours after administration ofNAC. There was a significant decrease in the mean systemic creatinineconcentration (p < 0.05). The cystatin C concentrations,however, did not change significantly. Thus, it may be that NAChas a direct effect on the systemic creatinine concentration,whereas it has no effect on preventing contrast-induced nephrotoxicity [6, 7].

Several reports now suggest cystatin C to be a reliable markerof GFR [8]. The study of Poletti et al. [5] adds to this suggestion.Before the protective effects of any agent against contrast material–inducednephrotoxicity are considered, the direct effects thereof oncreatinine levels should be assessed. In addition, future trials regardingprotective measures against contrast-induced nephrotoxicityshould preferentially be measured directly—or at leastadditional markers of the renal function (such as cystatin Cconcentrations) have to be assessed.

References

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