Kilpatrick Eric S, Butler Alexandra E, Atkin Stephen L, Sacks David B
Department of Clinical Biochemistry, Manchester Royal Infirmary, Manchester, United Kingdom.
Department of Postgraduate Studies and Research, Royal College of Surgeons in Ireland, Busaiteen, Bahrain.
Clin Chem. 2023 Apr 28;69(5):519-524. doi: 10.1093/clinchem/hvad020.
Currently, no authoritative guidelines exist recommending the analytical performance specification (APS) of blood beta-hydroxybutyrate (BOHB) testing in order to meet the clinical needs of patients. This study has applied existing diabetic ketoacidosis (DKA) BOHB diagnostic thresholds and the recommended rates of fall in BOHB concentrations during DKA treatment to establish pragmatic APSs for BOHB testing.
Required analytical performance was based on 2 clinical requirements: (a) to reliably distinguish between non-adjacent DKA BOHB diagnostic categories of <0.6, 0.6 to 1.5, 1.6 to 2.9, and ≥3 mmol/L, and (b) to be assured that a measured 0.5 mmol/L reduction in BOHB indicates the true concentration is at least falling (meaning >0 mmol/L decline).
An analytical coefficient of variation (CV) of <21.5% could reliably distinguish all non-adjacent diagnostic categories with >99% certainty, assuming zero bias. In contrast, within-day CVs of 4.9%, 7.0%, and 9.1% at 3 mmol/L BOHB were required to assure truly falling ketone concentrations with 99% (optimal), 95% (desirable), and 90% (minimal) probability, respectively. These CVs are larger at lower BOHB concentrations and smaller at higher concentrations.
Reliable tracking of changes in BOHB during DKA treatment largely drives the requirement for analytical performance. These data can be used to guide minimal, desirable, and optimal performance targets for BOHB meters and laboratory assays.
目前，尚无权威指南推荐血β-羟基丁酸（BOHB）检测的分析性能规范（APS）以满足患者的临床需求。本研究应用现有的糖尿病酮症酸中毒（DKA）BOHB诊断阈值以及DKA治疗期间BOHB浓度推荐的下降速率，来建立BOHB检测实用的APS。
所需的分析性能基于两项临床要求：（a）可靠区分<0.6、0.6至1.5、1.6至2.9以及≥3 mmol/L的非相邻DKA BOHB诊断类别，（b）确保测得的BOHB下降0.5 mmol/L表明真实浓度至少在下降（即下降>0 mmol/L）。
假设零偏差，分析变异系数（CV）<21.5%能够以>99%的确定性可靠区分所有非相邻诊断类别。相比之下，在BOHB浓度为3 mmol/L时，日内CV分别为4.9%、7.0%和9.1%，才能分别以99%（最佳）、95%（理想）和90%（最低）的概率确保酮浓度真正下降。这些CV在较低BOHB浓度时较大，在较高浓度时较小。
DKA治疗期间对BOHB变化的可靠追踪在很大程度上推动了对分析性能的要求。这些数据可用于指导BOHB血糖仪和实验室检测的最低、理想和最佳性能目标。
