Vitamin B12 deficiency: correction of P-methylmalonic acid for estimated glomerular filtration rate to improve diagnostic value – a confirmatory study

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.

Keywords:

• Vitamin B12
• methylmalonic acid
• estimated glomerular filtration rate
• kidney dysfunction
• vitamin B12 deficiency

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

J.F. Arendt has received a speaker’s fee on two occasions within the last 24 months from Teva Denmark A/S. These fees have no relation to the present study. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.