Cellular Uptake of Vitamin B12 in Patients with Chronic Renal Failure

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Abstract
Elevated concentration of plasma homocysteine (tHcy) is common in renal patients, however, the reason behind the resistance to vitamin B(12) and folate therapy are poorly understood. We investigated vitamin B12 uptake by mononuclear cells (MC) from predialysis patients (n = 19) as compared to healthy controls (n = 15). Serum levels of tHcy, methylmalonic acid and cystathionine, holotranscobalamin (holoTC), total vitamin B12 and folate were also measured. The uptake of vitamin B12 by MC from renal patients was lower than that by MC from controls (9.3 vs. 12.5 pg/3 x 10(6) cells; p = 0.001). Nonetheless, the receptor-binding capacity was comparable between patients and controls (6.1 vs. 6.5 pg/3 x 10(6) cells; p = 0.627). Average reduction of vitamin B12 uptake in patients as compared to the controls was 18.1%. Our results show that vitamin B12 uptake is impaired in MC from renal patients, with no evidence that the surface receptor is down-regulated. High serum concentrations of holoTC are common in renal patients and might be related to a generalized resistance to this vitamin. Serum concentrations of vitamin B12 within the reference range are not likely to ensure vitamin delivery into the cells. Supraphysiological doses of vitamin B12 may be necessary to deliver a sufficient amount of the vitamins to the cells via mechanisms largely independent of holoTC receptor.