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

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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.

TaalEngels
Pagina's685-692
TijdschriftAnnals of Clinical Biochemistry
Volume55
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - 1 nov 2018

Vingerafdruk

Methylmalonic Acid
Vitamin B Complex
Vitamin B 12
Testing
Data Mining
Data mining
Glomerular Filtration Rate
Linear regression

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    @article{dff65d7195754ee2aad7a6eea08420b9,
    title = "Improved testing for vitamin B12 deficiency: correcting MMA for eGFR reduces the number of patients classified as vitamin B12 deficient",
    abstract = "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.",
    keywords = "data mining, decision support, methylmalonic acid, personalized laboratory medicine, renal failure, Vitamin B",
    author = "{van Loon}, {Saskia L.M.} and Wilbik, {Anna M.} and Uzay Kaymak and {van den Heuvel}, {Edwin R.} and Volkher Scharnhorst and Boer, {Arjen Kars}",
    year = "2018",
    month = "11",
    day = "1",
    doi = "10.1177/0004563218778300",
    language = "English",
    volume = "55",
    pages = "685--692",
    journal = "Annals of Clinical Biochemistry",
    issn = "0004-5632",
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    }

    TY - JOUR

    T1 - Improved testing for vitamin B12 deficiency

    T2 - Annals of Clinical Biochemistry

    AU - van Loon,Saskia L.M.

    AU - Wilbik,Anna M.

    AU - Kaymak,Uzay

    AU - van den Heuvel,Edwin R.

    AU - Scharnhorst,Volkher

    AU - Boer,Arjen Kars

    PY - 2018/11/1

    Y1 - 2018/11/1

    N2 - 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.

    AB - 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.

    KW - data mining

    KW - decision support

    KW - methylmalonic acid

    KW - personalized laboratory medicine

    KW - renal failure

    KW - Vitamin B

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    DO - 10.1177/0004563218778300

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    IS - 6

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