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Ann Clin Lab Sci. 2013 Summer;43(3):243-9.

Serum methylmalonic acid and holotranscobalamin-II as markers for vitamin B12 deficiency in end-stage renal disease patients.

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VA Medical Center-San Diego, San Diego, CA 92161, USA.



Vitamin replacement, particularly B vitamins, remains an important concern in end-stage renal disease (ESRD) patients undergoing chronic hemodialysis. Serum markers such as methylmalonic acid (MMA) and holoTranscobalamin (holoTC) used to detect vitamin B12 deficiency are affected by impaired renal function which makes the interpretation of these biomarkers difficult in ESRD patients. We investigated the role renal failure has on MMA and holoTC concentrations and evaluated using MMA and/or holoTC to identify B12 deficient patients.


We evaluated the utility of serum MMA and holoTC for its role in the detection of vitamin B12 deficiency in dialysis patients (n=17) by using the reduction of MMA concentrations as a marker of the response to vitamin B12 treatment (1 mg, intramuscular injections once per month for 3 months). Nerve conduction studies (NCS) were done before and after vitamin B12 treatments to evaluate for any alteration in peripheral sensorimotor nerve function within a subset of the cohort.


Receiver operating characteristic curves for detection of vitamin B12 deficiency in dialysis patients showed that serum MMA concentrations had the greatest predictive potential (area under the curve = 0.792, p = 0.043) with an optimal cutoff of 750 nmol/L. Dialysis patients (n=10) with pre-MMA > 750 nmol/L and pre-HoloTC < 260 pmol/L showed a significant response to the vitamin B12 treatment (a mean MMA reduction of 461 nmol/L after B12 supplementation; p = 0.006).


MMA is viable marker of B12 deficiency in ESRD patients. Holo TC has potential as a supplementary marker with MMA to predict the response of vitamin B12 supplementation. Future studies on MMA and B12 should be done to confirm these findings in larger cohorts and to identify individuals who may benefit from vitamin B12 supplementation.


Methylmalonic acid; end-stage renal disease; holotranscobalamin; vitamin B12

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