van Loon Saskia Lm, Wilbik Anna M, Kaymak Uzay, van den Heuvel Edwin R, Scharnhorst Volkher, Boer Arjen-Kars
1 Department of Clinical Chemistry, Catharina Hospital, Eindhoven, The Netherlands.
2 Expert Center Clinical Chemistry, Eindhoven, The Netherlands.
Ann Clin Biochem. 2018 Nov;55(6):685-692. doi: 10.1177/0004563218778300. Epub 2018 Jun 6.
Background Methylmalonic acid (MMA) can detect functional vitamin B deficiencies as it accumulates early when intracellular deficits arise. However, impaired clearance of MMA from blood due to decreased glomerular filtration rate (eGFR) also results in elevated plasma MMA concentrations. Alternative to clinical trials, a data mining approach was chosen to quantify and compensate for the effect of decreased eGFR on MMA concentration. Methods Comprehensive data on patient's vitamin B, eGFR and MMA concentrations were collected ( n = 2906). The relationship between vitamin B, renal function (eGFR) and MMA was modelled using weighted multiple linear regression. The obtained model was used to estimate the influence of decreased eGFR on MMA. Clinical impact was examined by comparing the number of patients labelled vitamin B deficient with and without adjustment in MMA. Results Adjusting measured MMA concentrations for eGFR in the group of patients with low-normal vitamin B concentrations (90-300 pmol/L) showed that the use of unadjusted MMA concentrations overestimates vitamin B deficiency by 40%. Conclusions Through a data mining approach, the influence of eGFR on the relation between MMA and vitamin B can be quantified and used to correct the measured MMA concentration for decreased eGFR. Especially in the elderly, eGFR-based correction of MMA may prevent over-diagnosis of vitamin B deficiency and corresponding treatment.
甲基丙二酸（MMA）可检测功能性维生素B缺乏，因为当细胞内出现缺乏时，它会早期蓄积。然而，由于肾小球滤过率（eGFR）降低导致MMA从血液中清除受损，也会导致血浆MMA浓度升高。作为临床试验的替代方法，选择了一种数据挖掘方法来量化和补偿eGFR降低对MMA浓度的影响。方法：收集了患者维生素B、eGFR和MMA浓度的综合数据（n = 2906）。使用加权多元线性回归对维生素B、肾功能（eGFR）和MMA之间的关系进行建模。所得模型用于估计eGFR降低对MMA的影响。通过比较调整MMA前后被标记为维生素B缺乏的患者数量来检查临床影响。结果：在维生素B浓度处于低正常范围（90 - 300 pmol/L）的患者组中，对测得的MMA浓度进行eGFR调整后发现，使用未调整的MMA浓度会使维生素B缺乏的估计值高估40%。结论：通过数据挖掘方法，可以量化eGFR对MMA与维生素B之间关系的影响，并用于校正因eGFR降低而测得的MMA浓度。特别是在老年人中，基于eGFR的MMA校正可能会防止维生素B缺乏的过度诊断及相应治疗。
