羟苯磺酸钙对肌氨酸氧化酶法检测肌酐的干扰

摘要

目的 分析肾功能不全患者服用羟苯磺酸钙后不同酶法血清肌酐存在较大差异的原因,探讨羟苯磺酸钙对肌氨酸氧化酶法检测肌酐的影响.方法 本研究是自身前-后对照研究.(1)体内干扰实验:选取2011年5月至10月黄石市第二医院10例慢性肾脏病患者,检测服用羟苯磺酸钙服用前及服用后1周血清肌氨酸氧化酶法肌酐(Scr1)、脱亚胺酶法肌酐(Scr2)、尿素(Urea)、半胱氨酸蛋白酶抑制剂C(Cystatin C),比较服药前后Scr1、Scr2、Urea、估算法GFR(eGFR)的差异.(2)体外干扰筛选实验:检测羟苯磺酸钙(100 mg/L)对Scr1及Scr2有无干扰.(3)干扰剂量效应实验:检测不同浓度羟苯磺酸钙(1.25 ～ 20.0 mg/L)对肌氨酸氧化酶法低浓度肌酐(65.9 μmol/L)样品及高浓度肌酐(404.5 μmol/L)样品的干扰效应.以肌酐偏差3.5％或6.63 μmol/L作为干扰临床可接受标准(dmax),配对样本比较用Wilcoxonz秩和检验.结果 (1)体内干扰实验:患者服药后Scr1浓度148.0 μmol/L低于服药前273.5 μmol/L(Z=-2.803,P＜0.01),服药前、后Scr2浓度(269.5 μmol/L与266.0 μmol/L,Z=-0.614,P＞0.05)、Urea浓度(14.2 mmol/L与14.4 mmol/L,Z=-0.563,P＞0.05)及eGFR[18.95 ml· (min· 1.73 m2)-1与19.35 ml·(min·1.73 m2)-1,Z=-0.570,P＞0.05]差异均无统计学意义.(2)干扰筛选实验:Scr1对照样品均值404.0μmol/L,实验样品干扰值(dobs)95％置信区间(CI)为(-173.90±2.86)μmoL/L,显示严重负干扰,Scr2无干扰.(3)干扰剂量效应实验:低浓度肌酐样品,干扰剂量效应回归方程Y=0.0263X2-1.6394X-0.2754(R2=0.996,F=2546.7,P＜0.05),羟苯磺酸钙在3.5 mg/L浓度下干扰小于预设的dmax；高浓度肌酐样品,干扰剂量效应回归方程Y=-2.7649X-0.0782(R2=0.998,F=7943.4,P＜0.05),羟苯磺酸钙在4.4 mg/L浓度下干扰小于预设的dmax.结论 羟苯磺酸钙对肌氨酸氧化酶法检测肌酐有负干扰,是肾功能不全患者用药后不同酶法结果差异的原因,建议服用羟苯磺酸钙的肌酐结果在临床评价时需加以高度警惕,有条件时选用其他原理的肌酐测定法复核.%Objective To investigate the interference effect of calcium dobesilate on serum creatinine levels by Sarcosine oxidase-based assay.Methods 1.Interference test in vivo:Ten patients with chronic renal diseases from Huangshi second hosptial were recruited.Serum creatinine (sarcosine oxidase method,Scr1 ; deiminase method,Scr2),urea,and cystatin C were detected and compared before and after one week administration of calcium dobesilate; 2.Interference test in vitro:to detect whether 100 mg/L calcium dobesilate has any interference with Scr1 and Scr2; 3.Dose-dependent interference test:To detect the interference effect of different concentrations of calcium dobesilate (1.25-20.0 mg/L) on different creatinine concentrations (404.5 μmol/L or 65.9 μmoL/L) measured by sarcosine oxidase assay.Bias within 3.5％ or 6.63 μmol/L of creatinine levels was clinically acceptable.Statistical comparisons were made using Wilcoxon rank-sum test.Results There was significant difference of sarcosine oxidase-based serum creatinine levels between before and after one week administration of calcium dobesilate (P ＜ 0.05),while no significant differences were observed for deiminase-based serum creatinine levels,urea and estimated GFR values (P ＞ 0.05).Interference test showed that 95％ confidence interval of interventional value (Dobs) of calcium dobesilate (100 mg/L) was (-173.9 ± 2.86) μmol/L for the sarcosine oxidase assay and (1.21 ± 3.14) μmol/L for deiminase method,indicating that calcium dobesilate caused a significant negative effect on the former enzymatic assay but not the latter one.In the dose effect interference test of calcium dobesilate,the regression equations were:Y =-2.7649X-0.0782 (R2 =0.998,F =7943.4,P =0.000) for high creatinine levels and Y =0.0263X2-1.6394X-0.2754 (R2 =0.996,F =2546.7,P =0.000) for low creatinine levels.The interference effect was less than the predetermined d with the calcium dobesilate concentrations of 4.4 mg/L in high concentration specimen and 3.5 mg/L in low concentration specimen.Conclusions Calcium dobesilate has a significant negative interference with serum creatinine detected by the sarcosine oxidase method,which leads to the bias of creatinine in patients with renal insufficiency.Hence,sarcosine-oxidase-based creatinine levels should be cautious when calcium dobesilate was used,and further check with another assay is necessary if possible.