Abstract

Objectives: For diagnosis of vitamin B12 deficiency, plasma methylmalonic acid (P-MMA) is considered superior to plasma vitamin B12 (P-B12). Reduced kidney function elevates P-MMA, hence, hampering P-MMA as a biomarker. We assessed whether correcting P-MMA for estimated glomerular filtration rate (eGFR) can affect the estimated prevalence of B12 deficiency. Methods: We included 115,245 patients with concomitant measurements of P-MMA, P-B12 and P-Creatinine. B12 deficiency was classified using P-MMA decision limits at >0.75 and >0.43 µmol/L. The non-linear relation between eGFR and P-MMA was estimated using spline regression. We calculated the percentage-wise reclassification of B12 deficiency by using an eGFR corrected P-MMA formula with eGFR reference points of 90 and 60 mL/min. Results: 6% with B12 deficiency were reclassified as non-deficient after adjusting for eGFR (reference point eGFR 90 mL/min) with both P-MMA decision limits. Overall B12 deficiency prevalence was reduced from 9.6% to 9.0% (P-MMA decision limit 0.43 µmol/L). With P-MMA decision limits at 0.75 and 0.43 µmol/L, 33.6% and 44.8% of B12 deficient patients with an eGFR <60 mL/min were reclassified as non-deficient. Conclusions: We have demonstrated that correcting P-MMA for eGFR can reclassify P-MMA levels across decision limits for diagnosing B12 deficiency, in particular for patients with reduced kidney function. This may have clinical implications for avoiding overdiagnosis of this chronic disease.

摘要

目的：对于维生素 B12 缺乏症的诊断，血浆甲基丙二酸 (P-MMA) 被认为优于血浆维生素 B12 (P-B12)。肾功能降低会升高 P-MMA，因此阻碍了 P-MMA 作为生物标志物。我们评估了校正估计肾小球滤过率 (eGFR) 的 P-MMA 是否会影响 B12 缺乏症的估计患病率。方法：我们纳入了 115,245 名同时测量 P-MMA、P-B12 和 P-肌酐的患者。B12 缺乏使用 P-MMA 决策限在 >0.75 和 >0.43 µmol/L 进行分类。使用样条回归估计 eGFR 和 P-MMA 之间的非线性关系。我们使用 eGFR 校正的 P-MMA 公式计算了 B12 缺乏的百分比重新分类，eGFR 参考点为 90 和 60 mL/min。结果： 6% 的 B12 缺乏症患者在调整了 eGFR（参考点 eGFR 90 mL/min）和 P-MMA 决策限后被重新归类为非缺乏症。总体 B12 缺乏患病率从 9.6% 降低到 9.0%（P-MMA 决定限值 0.43 µmol/L）。P-MMA 决定限分别为 0.75 和 0.43 µmol/L，33.6% 和 44.8% 的 B12 缺乏且 eGFR <60 mL/min 的患者被重新归类为非缺乏。结论：我们已经证明，针对 eGFR 校正 P-MMA 可以在诊断 B12 缺乏的决策范围内重新分类 P-MMA 水平，特别是对于肾功能降低的患者。这可能对避免过度诊断这种慢性疾病具有临床意义。