Special reports from Qian Sun, PhD, DABCC, Technical Director of Automated Chemistry, Beaumont Health, Assistant Professor of Pathology, Oakland University William Beaumont School of Medicine; Jieli Shirley Li, MD, PhD, DABCC, NRCC. Co-Director of Clinical Chemistry and Toxicology Laboratory, Wexner Medical Center, Assistant Professor of Pathology, The Ohio State University.
Serum creatinine concentration is a primary component of Bedside Schwartz equation to provide the estimated glomerular filtration rate (eGFR) in children. To standardize creatinine measurement, most manufacturers have adopted calibration procedures that are traceable to isotope dilution mass spectrometry (IDMS) using the National Institute of Standards and Technology’s reference material [1, 2]. However, a reference material representing the much lower creatinine concentrations seen in children is not available, and it is unclear how well commercial creatinine assays perform at lower pediatric levels.
In a study led by Dr. Qian Sun at Beaumont Health, Dr. Shirley Li at the Ohio State University, and clinical chemists from the University of Michigan and the University of Chicago, the performance of six commercial creatinine assays was evaluated using IDMS traceable serum samples at concentrations seen in pediatric patients . The methods evaluated in the study include Roche Jaffe, Roche enzymatic, Abbott Jaffe, Abbott enzymatic, Siemens Jaffe, and Beckman Jaffe. Furthermore, creatinine measurements from 1971 pediatric patients were compared between the Abbott Jaffe and Abbott enzymatic methods. Using the IDMS traceable samples, the greatest inter-assay variability was seen in the sample with the lowest creatinine level (target value 0.273 mg/dL), where 67% of methods failed to reach the minimal bias specification of 8% (bias ranging from -7.5% to 86%). For the other samples with higher creatinine targets (0.440-0.634 mg/dL), two methods failed to meet the minimal bias specification, whereas the other four methods showed bias <8%. Substantial difference was also observed in creatinine measurements between Abbott Jaffe and Abbott enzymatic methods using patient samples.
The study showed that many commonly used creatinine assays remain inaccurate for the pediatric population after more than a decade of nationwide efforts to standardize creatinine measurements. When the creatinine-based eGFR is used for chronic kidney disease (CKD) staging in children, the large inter-assay variability can lead to disease misclassification, inappropriate diagnostic, and therapeutic interventions.
血清肌酐浓度是 Bedside Schwartz 方程的主要组成部分，用于估算儿童肾小球滤过率 (eGFR) 。为了使肌酐测量标准化，大多数制造商采用了可溯源至同位素稀释质谱 (IDMS) 的校准程序，使用美国国家标准与技术研究院提供的参考物质 [1, 2]。然而，这些参考物质没有涵盖儿童人群中较为常见的低肌酐浓度，并且目前临床肌酐检测在较低浓度上的精准度仍有待评估。
在 Beaumont Health 的孙倩博士、俄亥俄州立大学的李捷莉博士以及密歇根大学和芝加哥大学的临床化学家领导的一项研究中，他们使用 IDMS 可追溯血清样本用六种临床肌酐检测方法评估了儿童肌酐水平的精准度 。这些检测方法包括 Roche Jaffe、Roche enzymatic、Abbott Jaffe、Abbott enzymatic、Siemens Jaffe 和 Beckman Jaffe。此外，该研究还对 1971 名儿童患者的肌酐测量值在 Abbott Jaffe 和 Abbott 酶检测法之间进行了比较。用 IDMS 可追溯样品进行比较时，其中室间差在肌酐水平最低的样品（目标值 0.273 mg/dL）上表现最严重。 六种临床肌酐检测方法中，有67% 的方法肌酐检测未能满足 8% 的最小偏差要求（偏差范围从-7.5% 至 86%）。对于其他肌酐浓度较高的样本 (0.440-0.634 mg/dL) ，有两种检测方法也未能满足最小偏差要求，其余四种检测方法偏差均 <8%。用Abbott Jaffe 和 Abbott 酶检测法检测儿童患者血清样本时，两种方法之间也有着显著差异。
该研究表明，过去十多年，尽管行业内在全美范围努力把肌酐检测方法标准化，但是很多常用的肌酐检测法在儿童人群仍然不够精准。预估肾小球滤过率是基于肌酐值计算的， 当它用于儿童慢性肾病 (CKD) 分期时，这种不同检测方法间的差异可能会导致分期错误，从而影响诊断和治疗。
Myers GL, Miller GW, Coresh J, Fleming J, Greenberg N, Greene T, Hostetter T, Levey AS, Panteghini M, Welch M, Eckfeldt JH (2006) Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem 52(1): 5-18.
Killeen AA, Ashwood ER, Ventura CB, Styer P (2013) Recent trends in performance and current state of creatinine assays. Arch Pathol Lab Med 137(4): 496-502.
Lao, K., Sykes, E., van Wijk, X. M. R., Li, J., Williams, J., Gherasim, C., & Sun, Q. (2021). Large inter-assay difference of serum creatinine in pediatric population: a threat to accurate staging of chronic kidney disease. Pediatr Nephrol. doi:10.1007/s00467-021-05335-x