Guo Xiuzhi, Hou Li'an, Cheng Xinqi, Zhang Tianjiao, Yu Songlin, Fang Huiling, Xia Liangyu, Qi Zhihong, Qin Xuzhen, Zhang Lin, Liu Qian, Liu Li, Chi Shuling, Hao Yingying, Qiu Ling
From the Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academic Medical Science and Peking Union Medical College (XG, LH, XC, SY, HF, LX, ZQ, XQ, LZ, QL, LL, SC, YH, LQ); and Beijing Hospital, National Center for Clinical Laboratories, Ministry of Health, Beijing, PR China (TZ).
Medicine (Baltimore). 2015 Jun;94(23):e905. doi: 10.1097/MD.0000000000000905.
The vasoprotective drug calcium dobesilate is known to interfere with creatinine (Cr) quantifications in sarcosine oxidase enzymatic (SOE) assays. The aim of this study was to investigate this interference in 8 different commercially available assays and to determine its clinical significance. In in vitro experiments, interference was evaluated at 3 Cr levels. For this, Cr was quantified by SOE assays in pooled serum supplemented with calcium dobesilate at final concentrations of 0, 2, 4, 8, 16, 32, and 64 μg/mL. Percent bias was calculated relative to the drug-free specimen. For in vivo analyses, changes in serum concentrations of Cr, cystatin C (CysC; a renal function marker), and calcium dobesilate were monitored in healthy participants of group I before and after oral calcium dobesilate administration. In addition, variations in interference were also examined among different SOE assays using serum obtained from healthy participants of group II. Lastly, Cr levels from the 10 patients treated with calcium dobesilate were measured using 4 SOE assays and liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) for comparison. Our in vitro analyses indicated that the presence of 8 μg/mL calcium dobesilate resulted in a -4.4% to -36.3% reduction in Cr serum concentration compared to drug-free serum for 8 SOE assays examined. In vivo, Cr values decreased relative to the baseline level with increasing drug concentration, with the lowest Cr levels obtained at 2 or 3 hours after drug administration in participants of group I. The observed Cr concentrations for participants in group II were reduced by -28.5% to -3.1% and -60.5% to -11.6% at 0 and 2 hours after administration related to baseline levels. The Cr values of 10 patients measured by Roche, Beckman, Maker, and Merit Choice SOE assays showed an average deviation of -20.0%, -22.4%, -14.2%, and -29.6%, respectively, compared to values obtained by LC-IDMS/MS. These results revealed a clinically significant negative interference with calcium dobesilate in all sarcosine oxidase-based Cr assays, but the degree of interference varied greatly among the assays examined. Thus, extra care should be taken in evaluating Cr quantification obtained by SOE assays in patients undergoing calcium dobesilate therapy.
已知血管保护药物羟苯磺酸钙会干扰肌氨酸氧化酶法（SOE）检测中的肌酐（Cr）定量。本研究的目的是调查8种不同市售检测方法中的这种干扰情况，并确定其临床意义。在体外实验中，在3个Cr水平下评估干扰情况。为此，通过SOE检测法对添加了终浓度为0、2、4、8、16、32和64μg/mL羟苯磺酸钙的混合血清中的Cr进行定量。相对于无药物标本计算偏差百分比。对于体内分析，在第一组健康参与者口服羟苯磺酸钙前后监测血清中Cr、胱抑素C（CysC；一种肾功能标志物）和羟苯磺酸钙的浓度变化。此外，还使用从第二组健康参与者获得的血清检查了不同SOE检测方法之间干扰的差异。最后，使用4种SOE检测方法和液相色谱 - 同位素稀释串联质谱法（LC-IDMS/MS）测量了10例接受羟苯磺酸钙治疗患者的Cr水平以进行比较。我们的体外分析表明，对于所检测的8种SOE检测方法，与无药物血清相比，存在8μg/mL羟苯磺酸钙会导致Cr血清浓度降低4.4%至36.3%。在体内，随着药物浓度增加，Cr值相对于基线水平下降，在第一组参与者中，给药后2或3小时获得最低Cr水平。第二组参与者在给药后0和2小时观察到的Cr浓度相对于基线水平分别降低了28.5%至3.1%和60.5%至11.6%。通过罗氏、贝克曼、迈瑞和优利特SOE检测法测量的10例患者的Cr值与通过LC-IDMS/MS获得的值相比，平均偏差分别为20.0%、22.4%、14.2%和29.6%。这些结果表明，在所有基于肌氨酸氧化酶的Cr检测中，羟苯磺酸钙存在具有临床意义的负干扰，但在所检测的检测方法中干扰程度差异很大。因此，在评估接受羟苯磺酸钙治疗患者的SOE检测法获得的Cr定量时应格外小心。
