Plasma folate conjugase activities and folate concentrations in patients receiving hemodialysis

Livant, E. J.; Tamura, Tsunenobu; Johnston, Kelley E.; Vaughn, William H.; Bergman, S. M.; Forehand, J.; Walthaw, J.

doi:10.1016/0955-2863(94)90031-0

Cited by 33 publications

(12 citation statements)

References 20 publications

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“…Recently, intravenous administration of 50 mg of folinic acid combined with 750 mg of pyridoxine per week has been shown to lead to a significant decrease (by 67%) in the mean plasma homocysteine concentration [27], while the use of 5-methyltetrahydrofolate, the readily available form of folate, at an oral dose of 105 mg/week also lowered significantly (by 70%) the homocysteine plasma concentration [28]. The greater effects observed with folinic acid and 5-methyltetrahydrofolate could be related to the presence of an abnormal metabolism of folate in uraemia, as suggested by Livant et al [29] who observed that plasma folate conjugase activities are reduced in haemodialysis patients by the presence of plasma inhibitors and by Retief et al [30] who observed that the intestinal absorption of 5-methyltetrahydrofolate is impaired in uraemia. Jennette and Goldman [31] also reported inhibition of the transmembrane folate transport in uraemia, probably mediated by anions which cumulate in this condition.…”

Section: Discussionsupporting

confidence: 52%

Reduction of the Homocysteine Plasma Concentration by Intravenously Administered Folinic Acid and Vitamin B<sub>12</sub> in Uraemic Patients on Maintenance Haemodialysis

et al. 2001

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Background: Hyperhomocysteinaemia is an independent cardiovascular risk factor which can induce vascular lesions, thus contributing to the early development of atherosclerosis. Low-dose folic acid supplementation reduces the pretreatment homocysteine plasma levels by 25–35%. Recent studies report that higher intravenous or oral administration of the active form of folic acid reduces the homocysteine plasma concentration by nearly 70%. The reduction could also be influenced by the thermolabile variant of methylenetetrahydrofolate reductase (tMTHFR) and by the dialysis modality. Methods: A cross-sectional clinical study was performed to evaluate the effect of a drug containing folinic acid and vitamin B₁₂ on the plasma homocysteine concentration and whether this variable could also be influenced by the presence of a genetic variant of the methionine pathway and the use of different dialysis modalities. The plasma homocysteine concentration was measured in 55 patients undergoing haemodialysis, 27 of whom have been treated intravenously for megaloblastic anaemia using a drug containing low concentrations of folinic acid and vitamin B₁₂ at the end of each dialysis session for 6 months. The presence of tMTHFR was sought by molecular analysis, and the role of the dialysis modality was also investigated. Results: The patients given the folic acid treatment had lower homocysteine plasma levels than those not so treated. The plasma homocysteine concentration was significantly higher in the tMRHFR homozygotes than in the patients with a normal genotype, significantly lower in the treated than in the untreated homozygotes, and significantly higher in the untreated homozygotes than in the untreated subgroup with a normal genotype. The homocysteine level was also significantly lower in the patients who underwent convective haemodialysis than in those who received standard bicarbonate dialysis. Conclusions: A drug containing low concentrations of folinic acid combined with vitamin B₁₂ using an intermittent intravenous regimen is effective in reducing the homocysteine plasma concentration in uraemic patients. The homocysteine levels seem also to depend on genotype and dialysis modality.

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Section: Discussionsupporting

confidence: 52%

Reduction of the Homocysteine Plasma Concentration by Intravenously Administered Folinic Acid and Vitamin B<sub>12</sub> in Uraemic Patients on Maintenance Haemodialysis

et al. 2001

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“…At present, most of the available data do not point to a major transsulphuration defect, but to a partly folate‐sensitive and a betaine‐insensitive homocysteine remethylation defect as the main cause of hyperhomocysteinaemia in ESRD patients. Additional findings that support this view are the demonstration of a decreased activity of folate conjugase in plasma of haemodialysis patients [ 27] and a defective membrane transport of folates in the presence of uraemic serum [ 28]. Studies with stable isotopes of methionine, which provide detailed information on homocysteine conversion rates, may be essential to elucidate the complex disturbances in homocysteine metabolism and the effects of vitamin therapies in patients with chronic renal failure.…”

Section: Discussionmentioning

confidence: 99%

Effect of folic acid and betaine on fasting and postmethionine‐loading plasma homocysteine and methionine levels in chronic haemodialysis patients

Guldener

Janssen

Meer

et al. 1999

Journal of Internal Medicine

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In chronic haemodialysis patients, fasting as well as postmethionine-loading plasma tHcy levels depend on folate status and decrease after folic acid therapy. Increased postload homocysteine levels in these patients therefore do not necessarily indicate an impaired transsulphuration capacity only; alternatively, folate may indirectly influence transsulphuration. The elucidation of the complex pathogenesis of hyperhomocysteinaemia in chronic renal failure requires further investigation.

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“…Thus, the recommendation for the treatment of hyperhomocysteinemia in patients with ESRD focuses on supplementation with folate either alone or in conjunction with other vitamins (24). An alternative disturbance in folate metabolism in ESRD might be an impaired transmembrane transport of folate and a decreased plasma folate conjugase activity (21,26). Folate conjugase cleaves polyglutamate forms of folate into biologically more active oligoglutamates or monoglutamates.…”

Section: Introductionmentioning

confidence: 98%

Homocysteine, Cystathionine, Methylmalonic Acid and B-Vitamins in Patients with Renal Disease

Herrmann

Schorr²,

Geisel³

et al. 2001

Clinical Chemistry and Laboratory Medicine

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Moderate hyperhomocysteinemia is very frequent in renal patients. Aside from homocysteine (HCY) itself, the metabolites methylmalonic acid (MMA) and cystathionine (CYS) supply further information about disturbances in HCY metabolism. In two groups of renal patients, transplant and hemodialysis patients, we measured HCY, MMA and CYS and evaluated their diagnostic value for impaired HCY metabolism due to vitamin deficiency and renal insufficiency. We investigated serum samples from 63 transplant patients and 38 patients undergoing hemodialysis. HCY, MMA and CYS were assayed by gas chromatography-mass spectrometry, vitamin B6 by HPLC, B12 and folate by chemiluminescence immunoassay. The determination of HCY, MMA, and CYS in renal patients provides specific information about intracellular disturbances of HCY metabolism. The frequency of increased metabolite levels in renal patients was much higher than the frequency of lowered vitamin concentrations in serum. Furthermore, the metabolite levels in transplant patients were only moderately increased, whereas they were strongly increased in patients on hemodialysis (HCY 19.2 vs. 28.8 micromol/l, MMA 292 vs. 1025 nmol/l, CYS 733 vs. 2711 nmol/l). Our findings may support the use of MMA determination in the diagnosis of vitamin B12 deficiency in renal patients. Compared to vitamin B12 deficiency, renal dysfunction itself appears to cause only a modest elevation in serum MMA. Regression analysis revealed that the moderate elevation of HCY and CYS in transplant patients is mainly a consequence of impaired remethylation of HCY to methionine with activated transsulfuration, whereas the mildly elevated MMA level is attributable to renal dysfunction. In patients on hemodialysis, all three metabolites were markedly elevated, indicating a strongly disturbed HCY metabolism. Based on a backward regression, we discovered that the HCY metabolism was strongly disturbed by renal insufficiency and vitamin deficiency. The markedly elevated HCY level was mainly attributable to functional vitamin B12 deficiency indicated by high MMA, and the strong CYS elevation was due to renal dysfunction and inhibition of this pathway by low levels of vitamin B6. In conclusion, besides HCY, the determination of MMA and CYS levels supports an early diagnosis of B-vitamin deficiency in renal patients. MMA is a more sensitive indicator of intracellular vitamin B12 deficiency than vitamin B12 in serum.

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Plasma folate conjugase activities and folate concentrations in patients receiving hemodialysis

Cited by 33 publications

References 20 publications

Reduction of the Homocysteine Plasma Concentration by Intravenously Administered Folinic Acid and Vitamin B<sub>12</sub> in Uraemic Patients on Maintenance Haemodialysis

Reduction of the Homocysteine Plasma Concentration by Intravenously Administered Folinic Acid and Vitamin B<sub>12</sub> in Uraemic Patients on Maintenance Haemodialysis

Effect of folic acid and betaine on fasting and postmethionine‐loading plasma homocysteine and methionine levels in chronic haemodialysis patients

Homocysteine, Cystathionine, Methylmalonic Acid and B-Vitamins in Patients with Renal Disease

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