Authors
Zhenghan Huang
Published in
Clinica chimica acta; international journal of clinical chemistry. Pages 122966. Nov 07, 2026. Epub Nov 07, 2026.
Abstract
Reflex methylmalonic acid (MMA) testing is usually guided by fixed B12 thresholds, which may fail when kidney function is impaired.
We analysed 10,174 NHANES 2011-2014 adults with complex-survey weighting. Four prespecified B12 cutoffs were compared with multivariable logistic models for elevated MMA (≥271 nmol/L) using decision curve analysis.
Weighted prevalence of elevated MMA was 8.9%. The 221 pmol/L cutoff had sensitivity 33.4% (9.4% at eGFR <45). Discrimination rose across a comparator ladder: dichotomised B12 0.623, continuous B12 0.690, B12 + eGFR 0.805, full model 0.819. ΔAUC over B12 alone was 0.128 (JKn 95% CI 0.100-0.157) overall and 0.052 (JKn 95% CI 0.032-0.071) with eGFR ≥60; post hoc temporal validation preserved discrimination (validation AUC 0.817). Grey-zone-refitted models retained discrimination (optimism-corrected AUC 0.71 for B12 + eGFR); frozen full-sample models were modest (AUC 0.651 two-variable, 0.669 full) and require local recalibration. At a 5% risk threshold the full model detected 83.2% of cases versus 33.4% for the cutoff-7.6 additional tests per additional case. Continuous-scale kidney-function interaction was sensitive to the test denominator (p = 0.028-0.096).
Single B12 thresholds had limited sensitivity and no kidney-stratified threshold system was supported or validated. A multivariable model-using only B12 and eGFR-showed better discrimination and apparent net benefit than fixed cutoffs. Post-hoc grey-zone refits showed gains, but the frozen full-sample model showed poor grey-zone calibration; external validation is required before clinical use.
PMID:
42998864
Bibliographic data and abstract were imported from PubMed on 08 Nov 2026.
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