Huang Johnny W, Lahey Brianna, Clarkin Owen J, Kong Jennifer, Clark Edward, Kanji Salmaan, McCudden Christopher, Akbari Ayub, J W Chow Benjamin, Shabana Wael, Hiremath Swapnil
The Ottawa Hospital, Ottawa, Ontario, Canada.
University of Ottawa, Ottawa, Ontario, Canada.
Kidney Int Rep. 2020 Dec 3;6(2):396-403. doi: 10.1016/j.ekir.2020.11.018. eCollection 2021 Feb.
N-acetylcysteine (NAC) is an antioxidant that can regenerate glutathione and is primarily used for acetaminophen overdose. NAC has been tested and used for preventing iatrogenic acute kidney injury or slowing the progression of chronic kidney disease, with mixed results. There are conflicting reports that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, we conducted a systematic review of the literature to determine whether there is an effect of NAC on kidney function as measured with serum creatinine and cystatin C.
A literature search was conducted to identify all study types reporting a change in serum creatinine after NAC administration. The primary outcome was change in serum creatinine after NAC administration. The secondary outcome was a change in cystatin C after NAC administration. Subgroup analyses were conducted to assess effect of creatinine assay (Jaffe vs. non-Jaffe and intravenous vs. oral).
Six studies with a total of 199 participants were eligible for the systematic review and meta-analysis. There was a small but significant decrease in serum creatinine after NAC administration overall (weighted mean difference [WMD], -2.80 μmol/L [95% confidence interval {CI} -5.6 to 0.0]; = 0.05). This was greater with non-Jaffe methods (WMD, -3.24 μmol/L [95% CI -6.29 to -0.28]; = 0.04) than Jaffe (WMD, -0.51 μmol/L [95% CI -7.56 to 6.53]; = 0.89) and in particular with intravenous (WMD, -31.10 μmol/L [95% CI -58.37 to -3.83]; = 0.03) compared with oral NAC (WMD, -2.5 μmol/L [95% CI -5.32 to 0.32]; = 0.08). There was no change in cystatin C after NAC administration.
NAC causes a decrease in serum creatinine but not in cystatin C, suggesting analytic interference rather than an effect on kidney function. Supporting this, the effect was greater with non-Jaffe methods of creatinine estimation. Future studies of NAC should use the Jaffe method of creatinine estimation when kidney outcomes are being reported. Even in clinical settings, the use of an enzymatic assay when high doses of intravenous NAC are being used may result in underdiagnosis or delayed diagnosis of acute kidney injury.
N-乙酰半胱氨酸（NAC）是一种抗氧化剂，可使谷胱甘肽再生，主要用于对乙酰氨基酚过量中毒。NAC已被测试并用于预防医源性急性肾损伤或减缓慢性肾病的进展，结果不一。有相互矛盾的报道称，NAC可能会人为降低测得的血清肌酐水平，而不改善肾功能，这可能是由于检测干扰所致。鉴于这些不一致的结果，我们对文献进行了系统综述，以确定NAC对血清肌酐和胱抑素C所测定的肾功能是否有影响。
进行文献检索，以确定所有报告NAC给药后血清肌酐变化的研究类型。主要结局是NAC给药后血清肌酐的变化。次要结局是NAC给药后胱抑素C的变化。进行亚组分析以评估肌酐检测方法（碱性苦味酸法与非碱性苦味酸法以及静脉注射与口服）的影响。
六项研究共199名参与者符合系统综述和荟萃分析的条件。总体而言，NAC给药后血清肌酐有小幅但显著的下降（加权平均差[WMD]，-2.80μmol/L[95%置信区间{CI}-5.6至0.0]；P = 0.05）。非碱性苦味酸法（WMD，-3.24μmol/L[95%CI -6.29至-0.28]；P = 0.04）的下降幅度大于碱性苦味酸法（WMD，-0.51μmol/L[95%CI -7.56至6.53]；P = 0.89），特别是静脉注射（WMD，-31.10μmol/L[95%CI -58.37至-3.83]；P = 0.03）与口服NAC（WMD，-2.5μmol/L[95%CI -5.32至0.32]；P = 0.08）相比。NAC给药后胱抑素C没有变化。
NAC导致血清肌酐下降，但胱抑素C没有变化，这表明是分析干扰而非对肾功能有影响。支持这一点的是，非碱性苦味酸法估算肌酐时这种影响更大。在报告肾脏结局时，NAC的未来研究应使用碱性苦味酸法估算肌酐。即使在临床环境中，当使用高剂量静脉注射NAC时采用酶法检测可能会导致急性肾损伤的漏诊或诊断延迟。
