Improved testing for vitamin B₁₂ deficiency: correcting MMA for eGFR reduces the number of patients classified as vitamin B₁₂ deficient

Background Methylmalonic acid (MMA) can detect functional vitamin B₁₂ 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 B₁₂, eGFR and MMA concentrations were collected ( n = 2906). The relationship between vitamin B₁₂, 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 B₁₂ deficient with and without adjustment in MMA. Results Adjusting measured MMA concentrations for eGFR in the group of patients with low-normal vitamin B₁₂ concentrations (90-300 pmol/L) showed that the use of unadjusted MMA concentrations overestimates vitamin B₁₂ deficiency by 40%. Conclusions Through a data mining approach, the influence of eGFR on the relation between MMA and vitamin B₁₂ 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 B₁₂ deficiency and corresponding treatment.