vitamin-b-12 and Kidney-Failure--Chronic

Increasingly, chronic kidney disease (CKD) is becoming an inevitable consequence of obesity, metabolic syndrome, and diabetes. As the disease progresses, and through dialysis, the need for and loss of water-soluble vitamins both increase. This review article looks at the benefits and possible risks of supplementing these vitamins with the treatment of CKD.. Data in the PubMed and Embase databases were analyzed. The keywords "chronic kidney disease", in various combinations, are associated with thiamin, riboflavin, pyridoxine, pantothenic acid, folates, niacin, cobalamin, and vitamin C. This review focuses on the possible use of water-soluble vitamin supplementation to improve pharmacological responses and the overall clinical condition of patients.. The mechanism of supportive supplementation is based on reducing oxidative stress, covering the increased demand and losses resulting from the treatment method. In the initial period of failure (G2-G3a), it does not require intervention, but later, especially in the case of inadequate nutrition, the inclusion of supplementation with folate and cobalamin may bring benefits. Such supplementation seems to be a necessity in patients with stage G4 or G5 (uremia). Conversely, the inclusion of additional B6 supplementation to reduce CV risk may be considered. At stage 3b and beyond (stages 4-5), the inclusion of niacin at a dose of 400-1000 mg, depending on the patient's tolerance, is required to lower the phosphate level. The inclusion of supplementation with thiamine and other water-soluble vitamins, especially in peritoneal dialysis and hemodialysis patients, is necessary for reducing dialysis losses. Allowing hemodialysis patients to take low doses of oral vitamin C effectively reduces erythropoietin dose requirements and improves anemia in functional iron-deficient patients. However, it should be considered that doses of B vitamins that are several times higher than the recommended dietary allowance of consumption may exacerbate left ventricular diastolic dysfunction in CKD patients.. Taking into account the research conducted so far, it seems that the use of vitamin supplementation in CKD patients may have a positive impact on the treatment process and maintaining a disease-free condition.

Topics: Ascorbic Acid; Dietary Supplements; Folic Acid; Humans; Kidney Failure, Chronic; Niacin; Renal Dialysis; Renal Insufficiency, Chronic; Thiamine; Vitamin B 12; Vitamin B Complex; Water

Patients with chronic kidney disease or end-stage renal disease experience tremendous cardiovascular risk. Cardiovascular events are the leading causes of death in these patient populations, thus the interest in non-traditional risk factors such as hyperhomocysteinemia, folic acid and vitamin B12 metabolism is growing. Hyperhomocysteinemia is commonly found in CKD patients because of impaired renal metabolism and reduced renal excretion. Folic acid, the synthetic form of vitamin B9, is critical in the conversion of homocysteine to methionine like vitamin B12. Folic acid has also been shown to improve endothelial function without lowering homocysteine, suggesting an alternative explanation for the effect of folic acid on endothelial function. Whether hyperhomocysteinemia represents a reliable marker of cardiovascular risk and cardiovascular mortality or a therapeutic target in this population remains unclear. However, it is reasonable to consider folic acid with or without methylcobalamin supplementation as appropriate adjunctive therapy in patients with CKD. The purpose of this review is to summarize the characteristics of homocysteine, folic acid, and vitamin B12 metabolism, the mechanism of vascular damage, and the outcome of vitamin supplementation on hyperhomocysteinemia in patients with CKD, ESRD, dialysis treatment, and in kidney transplant recipients.

Topics: Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Renal Dialysis; Vitamin B 12

Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo- or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection.

Topics: Betaine; Cardiovascular Diseases; Choline; Dietary Supplements; DNA Methylation; Eating; Epigenesis, Genetic; Folic Acid; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Methionine; Nutritional Physiological Phenomena; Renal Insufficiency, Chronic; Uremia; Vitamin B 12; Vitamin B 6

Homocysteine (Hcy) is methylated by methionine synthase to form methionine with methyl-cobalamin as a cofactor. The reaction demethylates 5-methyltetrahydrofolate to tetrahydrofolate, which is required for DNA and RNA synthesis. Deficiency of either of the cobalamin (Cbl) and/or folate cofactors results in elevated Hcy and megaloblastic anemia. Elevated Hcy is a sensitive biomarker of Cbl and/or folate status and more specific than serum vitamin assays. Elevated Hcy normalizes when the correct vitamin is given. Elevated Hcy is associated with alcohol use disorder and drugs that target folate or Cbl metabolism, and is a risk factor for thrombotic vascular disease. Elevated methionine and cystathionine are associated with liver disease. Elevated Hcy, cystathionine, and cysteine, but not methionine, are common in patients with chronic renal failure. Higher cysteine predicts obesity and future weight gain. Serum S-adenosylhomocysteine (AdoHcy) is elevated in Cbl deficiency and chronic renal failure. Drugs that require methylation for catabolism may deplete liver S-adenosylmethionine and raise AdoHcy and Hcy. Deficiency of Cbl or folate or perturbations of their metabolism cause major changes in sulfur amino acids.

Topics: Alcoholism; Amino Acids, Sulfur; Anemia, Megaloblastic; Biomarkers; Cardiovascular Diseases; Folic Acid; Folic Acid Deficiency; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Liver Diseases; Nutritional Status; Obesity; S-Adenosylhomocysteine; Vitamin B 12; Vitamin B 12 Deficiency

Patients affected by chronic kidney disease (CKD) or end-stage renal disease (ESRD) experience a huge cardiovascular risk and cardiovascular events represent the leading causes of death. Since traditional risk factors cannot fully explain such increased cardiovascular risk, interest in non-traditional risk factors, such as hyperhomocysteinemia and folic acid and vitamin B12 metabolism impairment, is growing. Although elevated homocysteine blood levels are often seen in patients with CKD and ESRD, whether hyperhomocysteinemia represents a reliable cardiovascular and mortality risk marker or a therapeutic target in this population is still unclear. In addition, folic acid and vitamin B12 could not only be mere cofactors in the homocysteine metabolism; they may have a direct action in determining tissue damage and cardiovascular risk. The purpose of this review was to highlight homocysteine, folic acid and vitamin B12 metabolism impairment in CKD and ESRD and to summarize available evidences on hyperhomocysteinemia, folic acid and vitamin B12 as cardiovascular risk markers, therapeutic target and risk factors for CKD progression.

Topics: Biomarkers; Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Risk Factors; Vitamin B 12

People with end-stage kidney disease (ESKD) have high rates of cardiovascular events. Randomised controlled trials (RCTs) of homocysteine-lowering therapies have not shown reductions in cardiovascular event rates in the general population. However, people with kidney disease have higher levels of homocysteine and may have different mechanisms of cardiovascular disease. We performed a systematic review of the effect of homocysteine-lowering therapies in people with ESKD.. To evaluate the benefits and harms of established homocysteine lowering therapy (folic acid, vitamin B6, vitamin B12) on all-cause mortality and cardiovascular event rates in patients with ESKD.. We searched Cochrane Kidney and Transplant's Specialised Register to 25 January 2016 through contact with the Information Specialist using search terms relevant to this review.. Studies conducted in people with ESKD that reported at least 100 patient-years of follow-up and assessed the effect of therapies that are known to have homocysteine-lowering properties were included.. Two authors independently extracted data using a standardised form. The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, incident cardiovascular disease (fatal and nonfatal myocardial infarction and coronary revascularisation), cerebrovascular disease (stroke and cerebrovascular revascularisation), peripheral vascular disease (lower limb amputation), venous thromboembolic disease (deep vein thrombosis and pulmonary embolism), thrombosis of dialysis access, and adverse events. The effects of homocysteine-lowering therapies on outcomes were assessed with meta-analyses using random-effects models. Prespecified subgroup and sensitivity analyses were conducted.. We included six studies that reported data on 2452 participants with ESKD. Interventions investigated were folic acid with or without other vitamins (vitamin B6, vitamin B12). Participants' mean age was 48 to 65 years, and proportions of male participants ranged from 50% to 98%.Homocysteine-lowering therapy probably leads to little or no effect on cardiovascular mortality (4 studies, 1186 participants: RR 0.93, 95% CI 0.70 to 1.22). There was no evidence of heterogeneity among the included studies (I² = 0%). Homocysteine-lowering therapy had little or no effect on all-cause mortality or any other of this review's secondary outcomes. All prespecified subgroup and sensitivity analyses demonstrated little or no difference. Reported adverse events were mild and there was no increase in the incidence of adverse events from homocysteine-lowering therapies (3 studies, 1248 participants: RR 1.12, 95% CI 0.51 to 2.47; I(2) = 0%). Overall, studies were assessed as being at low risk of bias and there was no evidence of publication bias.. Homocysteine-lowering therapies were not found to reduce mortality (cardiovascular and all-cause) or cardiovascular events among people with ESKD.

Topics: Aged; Cardiovascular Diseases; Cause of Death; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Renal Dialysis; Stroke; Venous Thrombosis; Vitamin B 12; Vitamin B 6; Vitamin B Complex

In the general population, increased homocysteine concentrations are a risk factor for cardiovascular disease and mortality. However, it is not known whether this also applies to patients with end-stage renal disease.. Meta-analysis of retrospective (11 studies including 1,506 individuals), prospective observational studies (12 studies including 1,975 individuals), and intervention trials (5 studies including 1,642 dialysis patients). Analyses were carried out separately, according to the study design.. Studies of patients with end-stage renal disease treated by means of hemodialysis or peritoneal dialysis.. Studies investigating the association between total homocysteine level and cardiovascular disease or total mortality or the influence of vitamin supplementation on cardiovascular or mortality risk.. In intervention studies, vitamin preparations with folic acid alone or in combination with other vitamins, such as vitamin B(12) and B(6), were used.. In retrospective studies, cases are patients with cardiovascular diseases. Outcomes for prospective observational and intervention studies are cardiovascular events and total mortality.. In retrospective studies, there was no significant overall difference in homocysteine concentrations between cases and controls (weighted mean difference in homocysteine, 2.82 micromol/L; 95% confidence interval [CI], -2.22 to 7.86; P = 0.3). The pooled overall risk estimate for prospective observational studies suggests no association between homocysteine level (5-micromol/L increase) and total mortality (hazard ratio [HR], 1.02; 95% CI, 0.93 to 1.12; P = 0.7), but there was an association with cardiovascular events (HR, 1.09; 95% CI, 1.03 to 1.14; P = 0.001). In subgroup analysis of patients not receiving vitamins, an increase in homocysteine level was associated with increased mortality (HR, 1.07; 95% CI, 1.02 to 1.13; P = 0.01). For intervention trials with B vitamins, there was a significant risk reduction for cardiovascular disease (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = 0.02), but no risk reduction for total mortality or the composite end point including total mortality (relative risk, 1.01; 95% CI, 0.88 to 1.15; P = 0.9).. Many studies are small, which may lead to the observed heterogeneity. Some intervention trials are neither placebo controlled nor randomized. Separate analyses for specific end points and patients treated by means of hemodialysis or peritoneal dialysis were not possible.. Total homocysteine level may be a risk factor for cardiovascular events and total mortality in patients with end-stage renal disease not receiving vitamin supplementation or folic acid food fortification. There may be a potential for reducing cardiovascular disease in this population by folic acid supplementation.

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Prospective Studies; Renal Dialysis; Retrospective Studies; Risk Factors; Vitamin B 12

Hyperhomocysteinemia is associated with CKD and increased cardiovascular risk. Treatment with folic acid and possibly vitamin B12 reduces homocysteine in renal insufficiency. At present there is no evidence of reduced mortality or morbidity following such treatment. This was confirmed in a recent study evaluating combined treatment with folic acid, B6 and B12 in chronic renal insufficiency and ESRD. While an ongoing study in renal transplant patients is anticipated, there is not sufficient evidence currently to recommend treatment of all chronic renal patients with folic acid, B6 or B12.

Topics: Drug Therapy, Combination; Evidence-Based Medicine; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Mecobalamin, one of the coenzyme forms of vitamin B(12), acts as an important cofactor in the activities of B(12)-dependent methyltransferases. Since the discovery of mecobalamin, it has been applied mainly in the treatment of hyperhomocysteinaemia and peripheral neuropathy. However, there is still lack of a systemic review on the clinical administration of mecobalamin and its potential mechanism.. To review the mechanism, clinical efficacy and safety of mecobalamin in the treatment of hyperhomocysteinaemia and peripheral neuropathy.. First, the potential mechanism, pharmacokinetics and metabolism of mecobalamin were clarified. In addition, the clinical administration including efficacy, safety and tolerability of mecobalamin as monotherapy or combined therapy in the treatment of hyperhomocysteinaemia and peripheral neuropathy were also detailed.. Although both monotherapy and combined therapy can lower plasma/serum homocysteine levels and improve the neuropathic symptoms, combined therapy with other B vitamins seems to be more effective. However, more precise, double-blind and randomised control studies are necessary to confirm the efficacy of mecobalamin on hyperhomocysteinaemia, peripheral neuropathy interaction, and cardiovascular, neurological and osteoporotic mortality or morbidity.

Topics: Aged; Alprostadil; Animals; Cobamides; Coenzymes; Diabetic Neuropathies; Drug Administration Routes; Drug Therapy, Combination; Female; Folic Acid; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Kidney Failure, Chronic; Male; Metformin; Methionine; Methyltransferases; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Renal Dialysis; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6

Studies of the general population have suggested that high homocysteine levels are associated with cardiovascular morbidity and mortality. In chronic kidney disease, homocysteine levels rise, and cardiovascular risk increases with declining kidney function. While some studies in this population have found an association between elevated homocysteine and cardiovascular risk, others have noted that this association is largely attenuated by adjustment for kidney function, and several studies of patients with kidney failure have found that lower homocysteine levels predict mortality. Homocysteine levels can be lowered with folate, vitamin B6 and vitamin B12. Three large, randomized, controlled trials of patients with pre-existing cardiovascular disease and two smaller, randomized, controlled trials of patients with kidney failure failed to detect any cardiovascular benefit from homocysteine-lowering vitamins. Several more interventional trials are ongoing, but the available data thus far do not support screening for or treatment of hyperhomocysteinemia.

Topics: Cardiovascular Diseases; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Risk Factors; Survival Rate; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Antimetabolites, Antineoplastic; Drug Administration Schedule; Folic Acid; Glomerular Filtration Rate; Glutamates; Guanine; Humans; Kidney Failure, Chronic; Neoplasms; Pemetrexed; Vitamin B 12

Topics: Humans; Kidney Failure, Chronic; Renal Dialysis; Vitamin B 12; Vitamin B 12 Deficiency

The importance of sulfur amino acid metabolism has become increasingly apparent in recent years. Methionine and cysteine are precursors of glutathione, which plays an important role in intracellular antioxidant/free radical defenses. Homocysteine is a non-protein-bound sulfur amino acid strongly implicated in the pathogenesis of several diseases. Both glutathione and homocysteine are affected by abnormalities in sulfur amino acid metabolism that occur in the clinical setting.. The Storch-Young model, which determines methionine turnover and homocysteine remethylation by means of a tracer methionine infusion, has been improved by using plasma homocysteine (rather than methionine) enrichment in the model. A complex new tracer method involving the use of tracer serine, methionine, and leucine has been described to determine the effects of folate or pyridoxine deficiency on sulfur amino acid-methyl transfer reactions in humans. The etiology of hyperhomocysteinemia in chronic renal failure is controversial; new concepts in this area are described. There is new interest in the subspecies of homocysteine in the circulation. A new method is described for measuring the extremely low plasma concentrations of reduced homocysteine, using gas chromatography-mass spectrometry. Plasma S-adenosylhomocysteine, measured by fluorescence high-performance liquid chromatography, has been suggested as being superior to homocysteine as a predictor of the risk of vascular disease.. This review highlights and critiques the above recent developments, and points out some of the complexities and pitfalls in designing and interpreting human metabolic studies involving the sulfur amino acids.

Topics: Amino Acids, Sulfur; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Glutathione; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Kinetics; Methionine; Methylation; Models, Biological; Radioisotope Dilution Technique; Vitamin B 12

Topics: Homocysteine; Humans; Kidney Failure, Chronic; Vitamin B 12

An elevated blood level of homocysteine (Hcy), a sulfur amino acid, is associated with increased cardiovascular risk. Hcy is generated from S-adenosylhomocysteine (AdoHcy), the demethylated product of S-adenosylmethionine (AdoMet) in transmethylation reactions. AdoHcy is a competitive inhibitor of AdoMet-dependent methyltransferases. AdoHcy accumulation is prevented by rapid metabolism of its products. Chronic renal failure (CRF) is almost constantly associated with hyperhomocysteinemia. It has been shown that: (1) AdoHcy concentration is significantly increased and the AdoMet-AdoHcy ratio is reduced in erythrocytes of patients with CRF; (2) erythrocyte membrane protein methyl esterification, catalyzed by the enzyme protein L-isoaspartyl O-methyltransferase (PCMT; EC 2.1.1.77), is reduced in CRF; PCMT catalyzes a repair reaction involved in the conversion of an isopeptide bond (detrimental to protein structure and function) into a normal peptide bond; (3) D-aspartate residues, a side product of protein methylation and repair, are significantly reduced in erythrocyte membrane proteins of patients with CRF; and (4) folate treatment significantly reduces plasma Hcy levels and improves AdoMet-AdoHcy ratios. Stable isotope studies recently confirmed that the rate of methyl transfer reactions is significantly reduced in uremia. Additional evidence, obtained by independent groups, is consistent with this interpretation. We recently found increased isoaspartyl content of circulating plasma protein levels, particularly albumin, which was only partially reduced after folate treatment, in uremia. This kind of molecular damage possibly is caused by protein increased intrinsic instability as a result of interference with the uremic milieu. In conclusion, Hcy is an uremic toxin involved in protein molecular damage through the inhibition of methylation reactions and protein PCMT-mediated repair.

Topics: Cardiovascular Diseases; Female; Glomerular Filtration Rate; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylation; Renal Dialysis; Risk Factors; Sex Factors; Uremia; Vitamin B 12; Vitamin B 6

Mild to moderate hyperhomocysteinemia (Hhcy) is observed in more than 90% of patients with end-stage renal disease (ESRD) undergoing maintenance dialysis and approximately 60% to 70% of chronic stable renal transplant recipients. The reported association between Hhcy and the development of arteriosclerotic cardiovascular disease may account, in part, for the disproportionate risk for cardiovascular morbidity and mortality in patients with chronic renal disease. Treatment with the recommended daily allowances of folic acid and vitamins B(6) and B(12), which consistently normalizes total homocysteine (tHcy) levels in the general population free of chronic renal disease, rarely results in the normalization of tHcy levels in patients with ESRD. A large number of investigations now have shown that even grossly supraphysiological doses of folic acid and vitamins B(6) and B(12) fail to normalize tHcy levels in more than 90% of dialysis-dependent patients with ESRD with baseline Hhcy. Conversely, such treatment consistently normalizes tHcy levels among hyperhomocysteinemic chronic stable renal transplant recipients or patients with mild to moderate renal insufficiency. A randomized, placebo-controlled, tHcy-lowering intervention trial involving approximately 4,000 chronic stable US renal transplant recipients (RO1 DK56486 01A2) will soon be underway to formally address the tenable hypothesis that tHcy-lowering treatment may reduce the risk for arteriosclerotic outcomes. Data from this trial should be applicable to patients with chronic renal insufficiency in general.

Topics: Folic Acid; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Kidney Transplantation; Tetrahydrofolates; Vitamin B 12; Vitamin B 6

Because of a potential association with cardiovascular disease, birth defects, and various other conditions, an elevation of tHcy plasma levels has gained broad interest. The majority of chronic renal failure patients present with hyperhomocysteinemia, the causes of which are not completely understood. An increasing number of studies addressed the treatment of hyperhomocysteinemia in chronic renal failure patients. Folic acid combined with vitamin B6 and vitamin B12 is more effective in lowering tHcy levels than either cofactor alone. The optimal dose of folic acid appears to be 1 mg orally per day. Intravenous application of vitamin B12, giving 1 to 1.5 mg per week may be more effective than therapy with 1 mg orally per day. The role of vitamin B6 is far from clear. It may play a role in combination with folic acid and/or vitamin B12. Finally, general screening for and treatment of hyperhomocysteinemia is not recommended.

Topics: Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Renal Replacement Therapy; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia refers to an elevated circulating level of the sulfur-containing amino acid homocysteine and has been shown to be a risk factor for vascular disease in the general population. In patients with renal failure, hyperhomocysteinemia is a common feature. The underlying pathophysiological mechanism for this phenomenon is unknown. Proposed mechanisms include reduced renal elimination of homocysteine and impaired nonrenal disposal, possibly because of inhibition of crucial enzymes in the methionine-homocysteine metabolism by the uremic milieu. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Several case-control and prospective studies have now indicated that hyperhomocystenemia is an independent risk factor for atherothrombotic disease in patients with predialysis and end-stage renal disease. In renal patients, plasma homocysteine concentration can be reduced by administration of folic acid in doses ranging from 1 to 15 mg per day. In more than 50% of the cases, however, the homocysteine concentration remains above 15 micromol/L. The effects of vitamin B12 or vitamin B6 are unclear. Large intervention trials are now needed to establish whether homocysteine-lowering therapy will reduce atherothrombotic events in patients with renal failure. These studies are now planned or are ongoing.

Topics: Adult; Arteriosclerosis; Cardiovascular Diseases; Case-Control Studies; Child; Endothelium, Vascular; Female; Folic Acid; Folic Acid Deficiency; Follow-Up Studies; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Life Tables; Male; Methionine; Peritoneal Dialysis; Prospective Studies; Pyridoxine; Renal Dialysis; Survival Analysis; Thrombophilia; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6 Deficiency

An elevated total homocysteine (tHcy) plasma concentration is associated with increased morbidity and mortality due to cardiovascular disease in the general population and in patients with impaired renal function. The prevalence of hyperhomocysteinaemia (plasma levels above 15 micromol/l) in the general population is less than 5% and can be as high as 50% in patients with vascular disease. In patients with renal insufficiency, elevated tHcy plasma levels are detected in 50 - 100% of the patients. Total homocysteine plasma levels can be lowered or normalised by folic acid and/or vitamin B(6) and vitamin B(12) supplementation. In patients with advanced chronic renal insufficiency or end-stage renal disease, hyperhomocysteinaemia is partially resistant to folic acid or vitamin therapy. However, higher tHcy plasma levels may also reflect tissue damage and the increase in Hcy after an acute incident such as stroke or myocardial infarction may be necessary for tissue repair mechanisms. This implies, that lowering tHcy may even be harmful to some patients. Currently, prospective studies are underway to clarify whether folate supplementation, with or without additional other vitamins, improves cardiovascular disease morbidity and mortality in the general population, as well as in renal failure patients. While population-wide screening for and treatment of hyperhomocysteinaemia is generally not recommended, treatment of high risk patients may be considered.

Topics: Animals; Cardiovascular Diseases; Clinical Trials as Topic; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Kidney Transplantation; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Pyridoxine; Renal Dialysis; Risk Factors; Vitamin B 12

Topics: Cardiovascular Diseases; Dietary Supplements; Folic Acid; Folic Acid Deficiency; Hematinics; Homocysteine; Humans; Kidney Failure, Chronic; Kidney Transplantation; Pyridoxine; Renal Dialysis; Vitamin B 12

Homocysteine is an intermediate amino acid formed during the metabolism of methionine, a sulfur-containing essential amino acid, and cleared by the kidneys. The two major acquired causes of increased homocysteine values are chronic renal failure and absolute or relative deficiencies of folate, vitamin B12 or vitamin B6, three vitamins involved in the normal metabolism of methionine. We studied 176 patients (97 men and 79 women with mean age 56.3 +/- 14.8 years) with end-stage renal disease on peritoneal or hemodialysis. Homocysteine concentrations averaged 26.6 +/- 1.5 mumol/liter in patients with renal failure as compared to 10.1 +/- 1.7 mumol/liter in normals. Abnormal values exceeded the 95th percentile for normal controls in 149 patients, giving an overall prevalence of homocysteinemia of 85%. There was preservation of the negative correlation between homocysteine and folate (r = -0.48), suggesting responsiveness in spite of impairment. Increased homocysteine concentrations were associated with an increased odds ration for atherosclerotic and thrombotic complications independent of other traditional risk factors and the length of time on dialysis. The odds ratio for vascular events with homocysteine levels was 2.9 (CI 1.4 to 5.8) for the upper two quintiles of homocysteine values compared to the lower three quintiles adjusted for age, gender, hypertension, diabetes, hypercholesterolemia, smoking and time on dialysis. These data indicate that plasma homocysteine values represent an independent risk factor for vascular events in patients on peritoneal and hemodialysis. The mechanism by which high homocysteine concentrations might cause vascular damage in patients with renal failure remains unclear.

Topics: Arteriosclerosis; Female; Folic Acid; Homocysteine; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Methionine; Middle Aged; Pyridoxine; Thrombosis; Vitamin B 12

Topics: Anemia; Bone Marrow; Erythrocytes; Erythropoiesis; Erythropoietin; Ferritins; Folic Acid; Hemoglobins; Hemorrhage; Hemostasis; Humans; Hypersplenism; Iron; Kidney Failure, Chronic; Kidney Transplantation; Renal Dialysis; Uremia; Vitamin B 12

The choice between hemodiafiltration (HDF) or high-flux hemodialysis (HD) to treat end-stage kidney disease remains a matter of debate. The duration of recovery time after treatment has been associated with mortality, affects quality of life, and may therefore be important in informing patient choice. We aimed to establish whether recovery time is influenced by treatment with HDF or HD.. Randomized patient-blinded crossover trial.. 100 patients with end-stage kidney disease were enrolled from 2 satellite dialysis units in Glasgow, United Kingdom.. 8 weeks of HD followed by 8 weeks of online postdilution HDF or vice versa.. Posttreatment recovery time, symptomatic hypotension events, dialysis circuit clotting events, and biochemical parameters.. Patient-reported recovery time in minutes, incidence of adverse events during treatments, hematology and biochemistry results, quality-of-life questionnaire.. There was no overall difference in recovery time between treatments (medians for HDF vs HD of 47.5 [IQR, 0-240] vs 30 [IQR, 0-210] minutes, respectively; P=0.9). During HDF treatment, there were significant increases in rates of symptomatic hypotension (8.0% in HDF vs 5.3% in HD; relative risk [RR], 1.52; 95% CI, 1.2-1.9; P<0.001) and intradialytic tendency to clotting (1.8% in HDF vs 0.7% in HD; RR, 2.7; 95% CI, 1.5-5.0; P=0.002). Serum albumin level was significantly lower during HDF (3.2 vs 3.3g/dL; P<0.001). Health-related quality-of-life scores were equivalent.. Single center; mean achieved HDF convection volume, 20.6L.. Patients blinded to whether they were receiving HD or HDF in a randomized controlled crossover study reported similar posttreatment recovery times and health-related quality-of-life scores.

Topics: Aged; Aged, 80 and over; beta 2-Microglobulin; Betaine; Cross-Over Studies; Female; Health Status; Hemodiafiltration; Humans; Hypotension; Interleukin-6; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Phosphates; Potassium; Quality of Life; Recovery of Function; Renal Dialysis; Single-Blind Method; Time Factors; United Kingdom; Urea; Vitamin B 12

Clinical studies have shown that hyper-homocysteinemia is a potent independent risk factor for cardiovascular diseases, and many different methods have been investigated for lowering it in hemodialysis (HD) patients. Our study investigated the effect of Vitamin B 12 supplementation on serum homocysteine levels in these patients. This randomized trial was conducted on 140 HD patients. They were randomly distributed by lottery method into two groups: intervention and control. In the intervention group, 100 μg/mL of Vitamin B 12 was intravenously injected two times a week, for eight weeks. No intervention was performed in the control group. Serum levels of homocysteine, hemoglobin (Hb), and hematocrit (Hct) were measured at the beginning and again after eight weeks (2 months) of treatment. About 91% of the patients had hyperhomocysteinemia (serum homocysteine >15 μmol/L). The median baseline levels of serum homocysteine in the intervention and control groups were 31.9 and 26.9 μmol/L, respectively (P = 0.1). After eight weeks, the median homocysteine level reduced significantly in the Vitamin B 12 group to 22.2 versus 28.4 μmol/L in control group (P = 0.006). The mean Hb and Hct also changed significantly during our study (12.3 vs. 11.4 g/dL; P = 0.003 and 37.9 vs. 35.3%; P = 0.02, respectively). Our results demonstrated the existence of a statistical negative relationship between Vitamin B 12 and serum levels of homocysteine. Detailed investigations with larger sample sizes and longer-term use of Vitamin B 12 are recommended.

Topics: Aged; Biomarkers; Dietary Supplements; Female; Hematocrit; Hemoglobins; Homocysteine; Humans; Hyperhomocysteinemia; Iran; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B Complex

Treatment with folic acid and vitamin B12 appears capable of reducing total plasma homocysteine levels (tHcy), but it is unknown whether vitamin B12 alone reduces tHcy values. In this study we investigate the effects of alternate vitamins supplementation on homocysteine levels in patients treated by diffusive and convective dialysis techniques.. 74 patients were randomized blindly into two groups of 37 subjects each. The first group was treated initially with vitamin B12 for 2 months and with folic acid for the following 2 months. The second group was treated initially with folic acid. A wash out period of 2 months followed the treatment in both groups.. Total homocysteine levels decreased in both groups following the alternate vitamins therapy and dialysis, without significant difference between diffusive and convective techniques. Surprisingly, after the wash-out period, tHcy increased remarkably, regardless of the dialysis procedure used. At the end of the study, folate levels showed a higher reduction with haemodialysis compared to haemodiafiltration. In contrast, vitamin B12 levels showed a significant increase using diffusive haemodialysis, confirming a decisive role of membrane performance.. In conclusion we show for the first time that, even if total homocysteine levels decreased in both dialysis procedures, the convective techniques demonstrate a superior capacity on the reduction of tHcy levels compared to the diffusive method. Moreover, the lower depletion of vitamin B12 by diffusive techniques could determine a higher reduction of folate levels, demonstrating the decisive role of the membrane performance in the treatment of this patients.

Topics: Adult; Aged; Aged, 80 and over; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Genotype; Hemodiafiltration; Homocysteine; Humans; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Renal Dialysis; Vitamin B 12; Vitamins; Young Adult

Serum asymmetric dimethylarginine (ADMA) levels are increased in maintenance hemodialysis patients, and this abnormality may increase cardiovascular risk. We investigated whether combined administration of oral folate and intravenous methylcobalamin in such patients is more beneficial than oral folate alone at decreasing circulating ADMA levels.. Randomized controlled trial.. Patients undergoing hemodialysis.. 40 patients were randomly assigned to 1 of 2 groups. For 3 weeks, they received supplementation with either folate alone (15 mg/d; n = 20; folate group) or coadministered folate (15 mg/d) and methylcobalamin (500 mug after each hemodialysis treatment 3 times weekly; n = 20; methylcobalamin group).. normalization of plasma homocysteine levels (<15 mumol/L), decrease in serum ADMA levels.. change in augmentation index in the carotid artery and ratios of S-adenosylmethionine to S-adenosylhomocysteine (as a transmethylation indicator) and dimethylamine to ADMA (as an indicator of ADMA hydrolysis).. Blood samples were collected under fasting conditions during the prehemodialysis procedure.. The proportion showing normalization of plasma homocysteine levels was much greater in the methylcobalamin group (18 of 20 patients; 90%) than in the folate group (6 of 20; 30%; P < 0.001). The percentage of decrease in ADMA levels was greater in the methylcobalamin than folate group (25.4% +/- 10.2% vs 13.2% +/- 11.2%; P < 0.001). The increase in ratio of S-adenosylmethionine to S-adenosylhomocysteine was not different between the 2 groups; however, the ratio of dimethylamine to ADMA was increased in only the methylcobalamin group (P = 0.04). Augmentation index was decreased in only the methylcobalamin group (P = 0.03).. This study had an open-label nature and did not examine long-term effects of homocysteine-normalizing therapy (no clinical end points).. Coadministration of intravenous methylcobalamin and oral folate in hemodialysis patients normalized hyperhomocysteinemia and decreased ADMA levels and arterial stiffness. We suggest that this regimen may have greater potential than folate alone to decrease cardiovascular risk in such patients.

Topics: Administration, Oral; Aged; Arginine; Cardiovascular Diseases; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Risk Factors; Vitamin B 12; Vitamin B Complex

Hemodialysis (HD) patients have a greatly increased risk of cardiovascular morbidity and mortality. For this reason, attempts are often made to normalize hyperhomocysteinemia. This randomized prospective study sought to determine which risk factors are predictors of mortality and whether high doses of folates or 5-methyltetrahydrofolate (5-MTHF) could improve hyperhomocysteinemia and survival in HD patients.. 341 patients were divided into two groups: group A was treated with 50 mg i.v. 5-MTHF, and group B was treated with 5 mg/day oral folic acid. Both groups received i.v. vitamin B(6) and B(12). By dividing patients into C-reactive protein (CRP) quartiles, group A had the highest survival for CRP <12 mg/l, whereas no survival difference was found for group B. CRP was the only predictive risk factor for death (RR 1.17, range 1.04-1.30, p = 0.02). Dialysis age, hyperhomocysteinemia, methylenetetrahydrofolate reductase polymorphism, albumin, lipoprotein (a) and folate did not influence mortality risk. Survival in group A was higher than that in group B, namely 36.2 +/- 20.9 vs. 26.1 +/- 22.2 months (p = 0.003).. Our results suggest that CRP, but not hyperhomocysteinemia, is the main risk factor for mortality in HD patients receiving vitamin supplements. Intravenous 5-MTHF seems to improve survival in HD patients independent from homocysteine lowering.

Topics: Aged; C-Reactive Protein; Female; Humans; Hyperhomocysteinemia; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Models, Biological; Risk; Risk Factors; Tetrahydrofolates; Vitamin B 12; Vitamin B 6

Elevated plasma homocysteine levels are reported to be associated with higher rates of vascular diseases. Plasma homocysteine increases in chronic kidney disease (CKD) and could contribute to the increased cardiovascular risk in CKD.. Participants aged 55 years or older with CKD, defined as estimated GFR<60 ml/min and at high cardiovascular risk, were randomly assigned to the combination of folic acid, 2.5 mg, vitamin B6, 50 mg and vitamin B12, 1 mg (n = 307) or placebo (n = 312) daily for 5 years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction and stroke.. Mean baseline plasma homocysteine was 15.9 +/- 7.3 micromol/l in the active treatment group and 15.7 +/- 5.7 micromol/l in placebo group and decreased to 11.9 +/- 3.3 micromol/l (P < 0.001) on active treatment (15.5 +/- 4.5 on placebo). Primary outcome events occurred in 90 participants (29.3%) on active therapy and in 80 (25.6%) on placebo (relative risk, 1.19; 95% confidence interval, 0.88-1.61; P = 0.25). There were no significant treatment benefits on death from cardiovascular causes (1.24; 0.84-1.83), myocardial infarction (1.10; 0.76-1.61) and stroke (1.00; 0.54-1.85). More participants in the active treatment group were hospitalized for heart failure (1.98; 1.21-3.26; P = 0.007) and for unstable angina (1.70; 1.02-2.83; P = 0.04). Incidence of primary outcome increased with decreasing GFR.. Active treatment with B vitamins lowered homocysteine levels in participants with CKD but did not reduce cardiovascular risk.

Topics: Aged; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Male; Vitamin B 12; Vitamin B 6

High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown.. To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease.. Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L).. Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo.. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients.. Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups.. Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease.. clinicaltrials.gov Identifier: NCT00032435.

Topics: Aged; Cause of Death; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Pyridoxine; Renal Insufficiency, Chronic; Vascular Diseases; Vitamin B 12; Vitamin B Complex

This phase I study was conducted to determine the toxicities, pharmacokinetics, and recommended doses of pemetrexed in cancer patients with normal and impaired renal function.. Patients received a 10-minute infusion of 150 to 600 mg/m2 of pemetrexed every 3 weeks. Patients were stratified for independent dose escalation by measured glomerular filtration rate (GFR) into four cohorts ranging from > or = 80 to less than 20 mL/min. Pemetrexed plasma and urine pharmacokinetics were evaluated for the first cycle. Patients enrolled after December 1999 were supplemented with oral folic acid and intramuscular vitamin B12.. Forty-seven patients were treated with 167 cycles of pemetrexed. Hematologic dose-limiting toxicities occurred in vitamin-supplemented patients (two; 15%) and non-supplemented patients (six; 18%), and included febrile neutropenia (four patients) and grade 4 thrombocytopenia (two patients). Nonhematologic toxicities included fatigue, diarrhea, and nausea, and did not correlate with renal function. Accrual was discontinued in patients with GFR less than 30 mL/min after one patient with a GFR of 19 mL/min died as a result of treatment-related toxicities. Pemetrexed plasma clearance positively correlated with GFR (r2 = 0.736), resulting in increased drug exposures in patients with impaired renal function. With vitamin supplementation, pemetrexed 600 mg/m2 was tolerated by patients with a GFR > or = 80 mL/min, whereas patients with a GFR of 40 to 79 mL/min tolerated a dose of 500 mg/m2.. Pemetrexed was well tolerated at doses of 500 mg/m2 with vitamin supplementation in patients with GFR > or = 40 mL/min. Additional studies are needed to define appropriate dosing for renally impaired patients receiving higher dose pemetrexed with vitamin supplementation.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Administration Schedule; Fatigue; Female; Folic Acid; Glutamates; Guanine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nausea; Neoplasms; Neutropenia; Pemetrexed; Thrombocytopenia; Vitamin B 12

Treatment with folic acid and vitamin B12 appears to be effective in lowering total plasma homocysteine (tHcy) concentrations, but whether vitamin B12 alone lowers tHcy in patients with normal vitamin B12 status is unknown. The aims of the present study were to explore the effect of individual supplementation with folic acid or vitamin B12 on tHcy concentrations in hemodialysis (HD) patients and to compare changes in tHcy concentrations with MTHFR genotype.. We recruited 200 HD patients (119 men) from the "Umberto I" Hospital (Frosinone, Italy) and the Dialysis Unit of University Hospital "Tor Vergata". These patients were randomized blindly into 2 groups of 100 each. Unfortunately, during the study, 36 patients in the first group and 16 in the second group died. The first group was treated initially with vitamin B12 for 2 months and with folic acid for a following 2 months. The second group was treated initially with folic acid and then with vitamin B12. Samples were drawn before administration of either, after the first and second periods, and again 2 months after treatment.. The concentrations of tHcy decreased in both groups after the consecutive vitamin therapies, and the decrease was genotype-dependent. The decrease was greater for the T/T genotype (P <0.05) and was more significant when the treatment was started with folic acid (P <0.01).. The alternating vitamin treatment demonstrated for the first time the importance of folate therapy and the secondary contribution of vitamin B12 in lowering tHcy in HD patients.

Topics: Aged; Female; Folic Acid; Genotype; Homocysteine; Humans; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Renal Dialysis; Vitamin B 12; Vitamin B Complex

Hyperhomocysteinemia is an independent risk factor for atherosclerotic vascular disease in chronic hemodialysis patients. This stratified randomized controlled trial was designed to measure the effect of high dose oral vitamin B6, vitamin B12, and folic acid on homocysteine levels, and to evaluate the effect on atherosclerosis as measured by Intima-Media Thickness (IMT) of carotid arteries.. Fifty-four chronic hemodialysis patients with hyperhomocysteinemia were randomized to receive oral 15 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12 daily (treatment group) or oral 5 mg folic acid alone (control group) for 6 months. Homocysteine level and IMT were measured in both groups.. At 6 months, homocysteine levels in the treatment group were significantly reduced from 27.94 +/- 8.54 to 22.71 +/- 3.68 mmol/l (p = 0.009) and were not significantly increased from 26.81 +/- 7.10 to 30.82 +/- 8.76 mmol/l in control group (p = 0.08). Mean difference between both groups was statistically significant (p = 0.002). There was no significant difference of IMT of carotid arteries, however, a tendency that the treatment group would have less thickness was observed (0.69 +/- 0.29 mm and 0.62 +/- 0.16 mm, p = 0.99).. Treatment of hyperhomocysteinemia in chronic hemodialysis patients with daily oral 15 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12 for 6 months decreases homocysteine levels and tends to reduce IMT of carotid arteries. A long term study for the prevention of atherosclerosis is warranted.

Topics: Atherosclerosis; Carotid Arteries; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Treatment Outcome; Ultrasonography; Vitamin B 12; Vitamin B 6

Plasma total homocysteine (tHcy) concentrations are markedly increased in end-stage renal disease and only partially corrected by folic acid supplementation. We and others have reported that cobalamin, administered parenterally, reduces plasma tHcy substantially below the lowest concentrations attainable with folic acid. We have now carried out a randomized controlled clinical trial to compare the plasma Hcy-lowering effect of 3 intravenous cyanocobalamin dose regimens in maintenance hemodialysis patients: 1 mg postdialysis every 28, 14, and 7 days in addition to routine oral vitamin B supplementation. All patients in the hemodialysis unit where the study was carried out routinely received 1 mg intravenous cyanocobalamin every month, so participants who were randomized to receive the vitamin every 28 days simply continued with their existing treatment program. Serum cobalamin and plasma tHcy concentrations in the control group did not change over the course of the study. As measured after 8 weeks of therapy, intravenous cyanocobalamin every 14 days increased serum cobalamin approximately 2.5-fold and reduced plasma tHcy by 11.5% ( P = .035) below the concentration previously attained with monthly administration, whereas treatment every 7 days increased serum cobalamin concentrations approximately 5-fold and reduced plasma tHcy by 11.0% ( P = .013). These results show that intravenous cyanocobalamin at 7- or 14-day intervals reduces plasma tHcy concentrations of hemodialysis patients below the levels brought about by prior long-term administration every 4 weeks and confirms that plasma tHcy lowering with parenteral cobalamin is a true pharmacological effect and not merely correction of a latent deficiency state.

Topics: Aged; Drug Administration Schedule; Homocysteine; Humans; Injections, Intravenous; Kidney Failure, Chronic; Middle Aged; Vitamin B 12

High levels of homocysteine (tHcy) are frecuent in MHD patients, and recognized as a risk factor for cardiovascular events. Vitamin supplements have been shown to lower serum Hcys, although optimal dose and efficacy is not well defined. Moreover, methylenetetrahydrofolate reductase (MTHFR) gene polymorphism can modulate its prevalence and response to treatment.. To evaluate efficacy and safety of two vitamin supplement regimens on Hcys serum levels over a 12 month period.. We conducted a prospective, randomised, double-blind trial in 60 stable MHD patients (68 +/- 13 years, 48% male, 50% diabetics). Patients were randomly assigned to one of two treatment regimens: 1) daily renal multivitamin containing folate (FA), vitamin B6 and B12 (5 mg, 10 mg and 0.4 mg respectively) (N = 27); and 2) supraphysiological daily doses (15 mg, 100 mg and 1 mg) (N = 33). These regimens were continued throughout the study period. Hcys levels were compared with a control group from the general population (N = 276) matched for age and gender.. demographic and clinical data, serum levels of Hcys, FA, B6, B12 at baseline and after 1, 3, 6 and 12 months of treatment; MTHFR gene polymorphism (PCRRT).. At baseline, global prevalence of hyperhomocysteinemia (tHcy > or = 15 micromol/L) was 100% in patients and 22% en controls. Hcys levels were significantly higher in patients versus controls (32.4 +/- 8.9 vs 12.9 +/- 6.8; P < 0.0001). Both regimens were equally effective in reducing Hcys levels. As a whole, Hcys levels were reduced by 23.6% (P < 0.001) after one month of treatment. The highest reduction was observed at the sixth month (28.3%, 32.4 +/- 8.9 vs 22.7 +/- 6.4, P < 0.001) and remained stable thereafter. However, only 12% of patients normalised their plasma levels after 12 months of therapy. The effect of treatment was not influenced by age, gender, diabetes, body weight or time on MHD. Reduction rate of tHcy levels was related to baseline tHcy level (r = 0.500, P < 0.001) and baseline FA levels (r = -0.332, P = 0.009). The MTHFR polimorfism did not significantly modified the effect of the treatment. No side effects were associated with either regimen.. Hyperhomocysteinemia is common in patients with conventional HD schedules and this is not related to vitamin deficiencies. Vitamin supplements significantly reduce Hcys levels in a sustained but suboptimal way. Supraphysiological doses did not improve the results. Further studies are requiered to demonstrate that this effect is associated with an improval in morbidity and mortality.

Topics: Aged; Aged, 80 and over; Cohort Studies; Diabetic Nephropathies; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Folic Acid; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Prospective Studies; Renal Dialysis; Treatment Outcome; Vitamin B 12; Vitamin B 6

End-stage renal disease (ESRD) is associated with marked hyperhomocysteinemia which is only partially corrected by folic acid and pyridoxine supplementation. We and others have reported that various forms of parenteral cobalamin reduce plasma total homocysteine (tHcy) concentrations of patients with ESRD substantially below the lowest levels attainable with folic acid. We here report a 16-week randomized controlled crossover trial which directly compared the Hcy-lowering effect of intravenous hydroxocobalamin (HC) with that of cyanocobalamin (CC). Folic acid- and vitamin B12-replete maintenance hemodialysis patients were randomly assigned to receive either 1 mg intravenous HC weekly for 8 weeks followed by CC for a further 8 weeks, or CC for 8 weeks followed by HC for 8 weeks. Hydroxocobalamin increased serum cobalamin concentrations 40-fold, whereas CC increased them only 10-fold, but both treatments reduced plasma tHcy concentrations similarly by 33% (P < .001). Crossover to the alternate form of the vitamin greatly affected the serum cobalamin concentration but was without further effect on the plasma tHcy concentration. These results confirm that weekly cobalamin injections lower plasma tHcy concentrations of hemodialysis patients well below the level attainable with folic acid. Hydroxocobalamin and CC are equipotent despite producing very different serum cobalamin concentrations.

Topics: Cross-Over Studies; Female; Homocysteine; Humans; Hydroxocobalamin; Kidney Failure, Chronic; Male; Vitamin B 12

Hyperhomocysteinemia is present in the majority of chronic hemodialysis patients. Treatment with folic acid, vitamin B12, and vitamin B6 cannot fully normalize plasma homocysteine concentrations (tHcy). Previously we have demonstrated the tHcy-lowering effect of creatine supplementation in an animal model of uremia (Kidney Int 64:1331-1337, 2003). The present study investigates the effects of creatine supplementation on tHcy in a vitamin-repleted chronic hemodialysis population.. Forty-five hemodialysis patients receiving folic acid and vitamin B6 and B12 were included. Patients were treated with creatine (2 g/day) or placebo during 2 treatment periods of 4 weeks, separated by a washout of 4 weeks. Plasma tHcy, creatine, Kt/V(urea), folic acid, vitamin B12, and routine biochemistry were determined, as well as the prognostic inflammatory and nutritional index.. All patients had elevated tHcy concentrations (21.2 +/- 5.6 micromol/L). Creatine treatment resulted in increased plasma and red blood cell creatine levels, documenting uptake of creatine. Creatine did not affect tHcy concentrations. There was no relationship between plasma creatine concentrations and tHcy concentrations. No changes in body weight, routine biochemistry, nutritional status, folic acid, or vitamin B12 were observed during the study.. Creatine supplementation at a rate of 2 g/day does not further decrease tHcy concentrations in chronic dialysis patients already treated with high dose folic acid, vitamin B6, and B12 supplementation.

Topics: Aged; Aged, 80 and over; Creatine; Cross-Over Studies; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Nutrition Assessment; Renal Dialysis; Vitamin B 12; Vitamin B 6

The genetic and environmental factors influencing catabolism of homocysteine in end-stage renal disease (ESRD) patients remain poorly understood. This study investigated how genetic and nutritional influences affect the response to high-dose vitamin B(12) and folate treatment in ESRD patients with hyperhomocysteinemia. We studied 81 hemodialysis patients with hyperhomocysteinemia (> 16 micromol/L) on varied doses of a multivitamin containing 1 mg of folic acid per day. After screening blood work, all patients were switched to daily multivitamin therapy including 1 mg of folic acid for 4 weeks. Vitamin B(12), 1 mg/d, was added for an additional 4 weeks. Patients were then randomized to receive folic acid or placebo. The influence of the 3 methylenetetrahydrofolate reductase (MTHFR) 677 C-->T genotypes on the efficacy of vitamin therapy was assessed. In addition, we investigated how the metabolic complications of ESRD, including the relationship between methylmalonic acid (MMA) and circulating glycine, may contribute to hyperhomocysteinemia. There was no significant difference in total homocysteine (tHcy) levels between the MTHFR 677 C-->T genotypes during the screening phase of the trial. Treatment with a daily multivitamin containing 1 mg folate significantly lowered tHcy levels in all patients by 19.2%. Further supplementation with 1 mg vitamin B(12) resulted in greater tHcy reduction among subjects with the MTHFR 677 T/T genotype (P<.01, T/T v C/C or C/T) while lowering MMA equally in all MTHFR genotypes. There was a significant positive correlation between plasma glycine levels and MMA (P <.05). High-dose vitamin therapy significantly lowers, but does not normalize, MMA and tHcy levels. The MTHFR genotype, while influencing homocysteine levels, was not responsible for the majority of the elevation in plasma tHcy.

Topics: Cysteine; Genotype; Glycine; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Methylenetetrahydrofolate Reductase (NADPH2); Methylmalonic Acid; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Threonine; Vitamin B 12

Plasma homocysteine is elevated in patients with end-stage renal disease (ESRD) and is a risk factor for cardiovascular disease. Folic acid has been shown to partially reduce homocysteine levels in dialysis patients. It is not known whether vitamin B12 reduces homocysteine independent of folic acid in patients who are not vitamin B12 deficient.. To determine whether 1 mg vitamin B12 lowers homocysteine in stable, chronic, haemodialysis patients independent of folic acid.. Twenty-eight haemodialysis patients were randomized to receive three doses of 1 mg vitamin B12 or 1 mL saline placebo in a double-blind fashion at 1-month intervals. Fasting plasma total homocysteine, folic acid, red-cell folate, vitamin B12 and haemoglobin levels were determined prior to each dose and 4 weeks after the final injection. The study was powered to detect a 30% reduction in homocysteine over the 3 months.. Both the two groups were well matched with respect to total homocysteine levels, folic acid, red-cell folate and vitamin B12 levels. Serum vitamin B12 levels were significantly higher in the treatment group compared to placebo (217.7 pmol/L; 95% confidence interval (CI) 103.0-332.5; P < 0.001) at the end of the trial but homocysteine levels were not significantly different (3.08 micromol/L; 95% CI -4.44-10.61; P= 0.406).. The administration of intramuscular vitamin B12 over a 3-month period does not result in any reduction of plasma homocysteine levels in haemo-dialysis patients independent of folate status, however reductions of <30% cannot be excluded by the present study. High-dose folic acid remains the treatment of choice in reducing homocysteine, but whether this results in a reduction in cardiovascular events remains to be determined.

Topics: Adult; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Injections, Intramuscular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Vitamin B 12

Renal failure causes hyperhomocysteinemia, an important risk factor for cardiovascular disease and venous access thrombosis in end-stage renal disease (ESRD). Folic acid is necessary for homocysteine (Hcy) metabolism, and therapy with 1 mg/d or more of folic acid reduces plasma total Hcy (tHcy) concentrations in ESRD, although seldom to normal. In contrast to folic acid, the Hcy-lowering effect of vitamin B(12) has not been well studied in ESRD. We performed a prospective randomized controlled clinical trial involving 24 maintenance hemodialysis patients with normal or supranormal serum folate and vitamin B(12) concentrations who received either standard therapy, which included 5 to 6 mg folic acid, 5 to 10 mg pyridoxine, and 6 to 10 microg oral vitamin B(12) per day, or standard therapy plus 1 mg hydroxocobalamin administered subcutaneously once per week after dialysis. Plasma tHcy and serum methylmalonic acid (MMA) concentrations were measured before and after 8 and 16 weeks of continuous treatment. Hydroxocobalamin reduced plasma tHcy by an average of 32% (P <.005) and serum MMA by an average of 19% (P <.001). The Hcy-lowering effect of hydroxocobalamin was independent of baseline serum vitamin B(12), folic acid, and MMA concentrations. Patients with higher baseline plasma tHcy concentrations had the greatest response (r = 0.80; P <.002). These results show that parenteral hydroxocobalamin reduces plasma tHcy dramatically in vitamin B(12)-replete hemodialysis patients. Persons with considerable persisting hyperhomocysteinemia despite high-dose folic acid therapy are likely to respond to the addition of hydroxocobalamin, irrespective of their serum vitamin B(12) concentrations.

Topics: Aged; Female; Folic Acid; Homocysteine; Humans; Hydroxocobalamin; Hyperhomocysteinemia; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Methylmalonic Acid; Middle Aged; Prospective Studies; Renal Dialysis; Treatment Outcome; Vitamin B 12

Ischemic heart disease and other complications of atherosclerosis are the usual cause of death in patients with chronic renal failure. Important factors associated with early onset of atherosclerosis in these patients are hyperhomocysteinemia, hyperfibrinogenemia, and elevated levels of lipoprotein(a) (Lp(a)). Folic acid (15 mg/d), pyridoxine (150 mg/d), and cyanocobalamin (1 mg/wk) were administered for 4 weeks in 21 patients receiving dialysis, and a simultaneous, statistically significant reduction in the concentration of homocysteine, fibrinogen, and Lp(a) was found. A positive correlation between decreasing homocysteine and fibrinogen levels was also noted. The parameters studied approached presupplementation values 6 months after vitamins were discontinued. The results suggest that vitamin supplementation has a favorable effect on risk factors of atherosclerosis in patients with renal failure and that interactions may exist between homocysteine, fibrinogen, and Lp(a).

Topics: Adult; Arteriosclerosis; Cholesterol; Creatinine; Drug Therapy, Combination; Female; Fibrinogen; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Lipoprotein(a); Male; Pyridoxine; Renal Dialysis; Risk Factors; Triglycerides; Urea; Uric Acid; Vitamin B 12; Vitamin B Complex

The authors found considerably lower plasma total homocysteine (tHcy) concentrations in patients with end-stage renal disease (ESRD) on maintenance hemodialysis, who routinely received high-dose parenteral vitamin B12, than in comparable patients receiving much higher doses of folic acid but only replacement-dose oral vitamin B12. They therefore sought prospective evidence that high-dose parenterally administered vitamin B12 may partially ameliorate renal failure-associated hyperhomocysteinemia.. Open phase 2 clinical trial.. Outpatient hemodialysis unit.. Fourteen clinically stable patients on maintenance hemodialysis with normal baseline serum vitamin B12 concentrations.. Three parenteral injections of 1 mg vitamin B12 given at 4-week intervals.. Plasma tHcy and serum vitamin B12 concentrations were measured before, during and 7 months after the termination of vitamin B12 therapy.. The mean (and standard error) baseline plasma tHcy was 26.5 (1.8) micromol/L. The plasma tHcy value fell successively after each vitamin injection to reach a value of 23.6 (1.6) micromol/L 1 month after the final injection (p < 0.05), while the serum vitamin B12 concentration increased from 471 (42) pmol/L to 890 (74) pmol/L (p < 0.05). Seven months after the final injection, the serum B12 concentration had fallen and tHcy had risen to near their original values.. Three monthly vitamin B12 injections modestly but distinctly reduced tHcy concentrations in hemodialysis patients whose prior vitamin B12 status was normal. Randomized placebo-controlled clinical trials of longer duration and using larger or more frequent parenteral doses are indicated to determine whether administration of this safe and inexpensive vitamin can improve hyperhomocysteinemia in ESRD.

Topics: Cysteine; Homocysteine; Humans; Hyperhomocysteinemia; Injections, Subcutaneous; Kidney Failure, Chronic; Methylmalonic Acid; Renal Dialysis; Vitamin B 12

Hyperhomocysteinemia occurs in nearly 100% of patients with end-stage renal disease (ESRD) and is associated with increased morbidity and mortality. Means to reduce elevated homocysteine concentrations is supplementation with folic acid, vitamin B6, and vitamin B12. However, doses of vitamins required for optimized treatment are subject of debate. Therefore, the effect of 2 different multivitamin preparations on the homocysteine concentrations in patients with ESRD were compared.. Patients received 3 times per week either 2 tablets of preparation A (800 microg folic acid, 6 microg vitamin B12, 10 mg vitamin B6), 2 tablets of preparation B (160 microg folic acid, no vitamin B12, 10 mg vitamin B6), or placebo for a period of 12 weeks with control of total homocysteine (tHcy) levels at baseline, and at 4, 8, and 12 weeks.. The study was performed at the University Hospital of Magdeburg, Germany in patients with ESRD treated with chronic intermittent maintenance hemodialysis.. Preparation A reduced the tHcy concentration significantly by nearly 50%, whereas preparation B did not change the tHcy concentration in comparison with placebo. However, tHcy was not normalized in the majority of patients receiving preparation A.. The reduction of tHcy achieved by a multivitamin containing 800 microg folic acid was substantial and even higher than the reduction reported in supplementation studies using higher doses of folic acid alone. Nevertheless, hyperhomocysteinemia in ESRD patients appears relatively refractory to vitamin supplementation, in contrast with results obtained in healthy volunteers.

Topics: Dietary Supplements; Dose-Response Relationship, Drug; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Pyridoxine; Renal Dialysis; Vitamin B 12

Hyperhomocyst(e)inemia is commonly accepted as an independent atherosclerotic risk factor. In most hemodialysis patients, serum homocyst(e)ine is markedly elevated and may contribute to premature atherosclerosis in these patients. Whereas the beneficial effect of folate supplementation on serum homocyst(e)ine has been extensively studied, there are less detailed studies on the effects of cobalamin and pyridoxal phosphate alone, or in combination with folate. We examined the effect of a four-week course of intravenous treatment with folate (1.1 mg), cobalamin (1.0 mg), and pyridoxal phosphate (5.0 mg), administered once (group 1), twice (group 2) or thrice (group 3) weekly in 33 hemodialysis patients divided in three groups of 11 patients. All patients were followed for a further four weeks after treatment was stopped. Serum homocyst(e)ine, cobalamin, folate and pyridoxal phosphate, as well as the metabolites of homocyst(e)ine, methylmalonate, 2-methylcitrate and cystathionine, were determined before, during and after treatment. Baseline serum homocyst(e)ine correlated significantly with serum folate (P=0.0149), cobalamin (P=0.0047) and pyridoxal phosphate (P=0.0408). Correlations independent from the other metabolites or vitamins were found for methylmalonate (P=0.003) and folate (P=0.029). All regimens increased serum cobalamin significantly (in group 1 from 444 +/- 215 to 17,303 +/- 11,989 pg/ml, P<0.01; in group 2 from 542 +/- 633 to 44,896 +/- 15,772 pg/ml, P<0.001; in group 3 from 548 +/- 394 to 77,961 +/- 31,546 pg/ml, P<0.001), but did not increase any of the other vitamin levels. Serum homocyst(e)ine was lowered significantly by 39.8% +/- 31.9% (P<0.05) with two and by 30.1% +/- 26.9% (P<0.05) with three vitamin dosages weekly, but not with one dosage weekly. Since methylmalonate is known to be a sensitive marker of cobalamin deficiency, the data support an important influence of cobalamin levels on baseline homocyst(e)ine levels. Increasing cobalamin levels and additional treatment with folate and pyridoxal phosphate 156 may decrease serum homocyst(e)ine in the same way as high doses of folate alone.

Topics: Female; Folic Acid; Hematinics; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pyridoxine; Regression Analysis; Renal Dialysis; Vitamin B 12; Vitamin B Complex

It is unclear whether total serum homocysteine (tHcy) and the C677T mutation of methylenetetrahydrofolate reductase (MTHFR) are associated with cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD).. A cross-sectional sample of 459 patients with ESRD on chronic dialysis was assessed to determine whether tHcy and the C677T mutation are associated with CVD prevalence in multiple logistic regression. As CVD mortality is high, we examined the relationship between homozygosity and duration of dialysis.. Mean tHcy was higher in patients without a history of CVD (35.2 micromol/L vs. 30.4 micromol/L, P = 0.02). In multivariate models, CVD was negatively associated with tHcy and positively associated with TT genotype, male gender, and body mass index. Mean tHcy levels were higher among those with the TT genotype compared with those with the CC genotype when adjusted for age, folate, creatinine, and albumin (37.9 micromol/L vs. 31.9 micromol/L, P = 0.005). Among whites, the prevalence of the TT genotype was higher in those having undergone less than one year of dialysis (P = 0.002).. The C677T genotype of MTHFR is associated with CVD in ESRD and may be a more meaningful marker than tHcy for abnormal homocysteine metabolism in ESRD. Prospective data from ongoing clinical trials are needed to improve our understanding of these findings. Screening for this polymorphism may help guide prevention measures.

Topics: Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Ethnicity; Female; Folic Acid; Genotype; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multivariate Analysis; Mutation; Oxidoreductases Acting on CH-NH Group Donors; Peritoneal Dialysis; Pyridoxine; Renal Dialysis; Risk Factors; Sex Factors; Vitamin B 12

Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 micromol/l vs 6.8 micromol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 micromol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B12 was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 micromol/l) than nondialyzed patients with the mutation (10.7 micromol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B12 less than 522 pmol/l. Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B12 status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are particularly at risk for hyperhomocysteinemia. Further studies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients.

Topics: Adolescent; Aging; Child; Child, Preschool; Diet; Female; Folic Acid Deficiency; Genotype; Homocysteine; Humans; Infant; Kidney Failure, Chronic; Kidney Function Tests; Male; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Reference Values; Renal Dialysis; Vitamin B 12

The excess of cardiovascular disease in end-stage renal disease (ESRD) patients is unexplained, but could relate to altered intrinsic vascular wall properties, such as increased arterial stiffness, which could be mediated by hyperhomocysteinemia. We investigated potential determinants of carotid artery stiffness in ESRD patients and the effect of long-term homocysteine-lowering treatment.. Fifty-four patients on maintenance dialysis treatment were studied at baseline. Fourty-one patients completed the treatment protocol, which consisted of a 12-week treatment with folic acid 5 mg daily with or without betaine 4 g per day, and of 1 or 5 mg of folic acid thereafter for 40 weeks. Both phases were randomized. Compliance and distensibility coefficients (CC and DC) and the stiffness index (beta) of the common carotid artery were determined at baseline and after 52 weeks of treatment using a non-invasive vessel wall movement detector system.. At baseline, plasma total homocysteine was elevated (44.1+/-33.7 micromol/l), but showed no relationship with CC, DC or beta. Age and mean arterial pressure (MAP) were the only independent determinants of CC and DC, whereas beta was associated with age only. Plasma homocysteine showed a sustained decrease after therapy (20.7+/-9.0 micromol/l at week 52). No significant changes occurred in CC (from 0.59+/-0.21 to 0.60+/-0.22 mm2/kPa; p = 0.47), in DC (from 14.9+/-6.1 to 15.3+/-6.2 10(-3)/kPa; p = 0.55), or in beta (from 10.9+/-4.7 to 11.2+/-4.4; p = 0.64). No independent determinants were detected for the change in CC, whereas the change in DC was inversely related to the change in MAP (stand. r = -0.58; p<0.0002). The decrease in MAP after therapy was significant (p = 0.003) and was related to the dialysis mode (p = 0.003) and smoking status (p = 0.02).. Folic acid treatment of hyperhomocysteinemia has no major effect on carotid artery stiffness in chronic dialysis patients. The results do, however, emphasize the importance of tight blood pressure control in these patients.

Topics: Age Factors; Analysis of Variance; Biomarkers; Blood Pressure; Brachial Artery; Carotid Artery, Common; Compliance; Endothelins; Homocysteine; Humans; Kidney Failure, Chronic; Pyridoxine; Regression Analysis; Renal Dialysis; Vasodilation; Vitamin B 12; von Willebrand Factor

Pharmacologic doses of folic acid are commonly used to reduce the hyperhomocysteinemia of end-stage renal disease (ESRD). Vitamin B12 acts at the same metabolic locus as folic acid, but information is lacking about the specific effects of high doses of this vitamin on homocysteine levels in renal failure. We therefore compared the plasma homocysteine concentrations of maintenance hemodialysis patients in two McGill University-affiliated urban tertiary-care medical centers that differed in the use of vitamin B12 and folic acid therapy. Patients in the first hemodialysis unit are routinely prescribed high-dose folic acid (HI-F, 6 mg/d), whereas those in the second unit receive high-dose vitamin B12 in the form of a monthly 1-mg intravenous injection, along with conventional oral folic acid (HI-B12, 1 mg/d). Predialysis homocysteine was 23.4 +/- 6.8 micromol/L (mean +/- SD) in the HI-F unit and 18.2 +/- 6.1 micromol/L in the HI-B12 unit (P < .002). Postdialysis homocysteine was 14.5 +/- 4.1 in the HI-F unit and 10.6 +/- 3.4 micromol/L in the HI-B12 unit (P = .0001). Multiple regression analysis indicated that high-dose parenteral vitamin B12 was associated with a lower homocysteine concentration even after controlling for the potential confounders of sex, serum urea, serum creatinine, urea reduction ratio, and plasma cysteine. Because this was a cross-sectional observational study, we cannot exclude the possibility that unidentified factors, rather than the different vitamin therapies, account for the different homocysteine levels in the two units. Careful prospective studies of the homocysteine-lowering effect of high-dose parenteral vitamin B12 in ESRD should be undertaken.

Topics: Aged; Chromatography, High Pressure Liquid; Cross-Sectional Studies; Cystine; Female; Fluorometry; Folic Acid; Hematinics; Hemodialysis Units, Hospital; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Regression Analysis; Vitamin B 12

High-flux haemodialysis (HD) has recently been vigorously promoted as a novel standard, and it can indeed efficiently reduce the occurrence of most uraemic symptoms due to middle molecular toxins and/or underdialysis. However, some symptoms remain problematical, particularly peripheral polyneuropathy (PPN). One of the possible reasons for this is that the patients may have low concentrations of some nutrients, e.g. vitamin B(6), necessary for normal peripheral neuron function.. Predialysis serum pyridoxal-5'-phosphate (P5P) level was determined in 36 chronic HD patients who were undergoing high-flux HD and receiving human recombinant erythropoietin. Among them, 26 patients suffered from PPN. Prior to supplementation, these 26 patients were examined and their neurological symptoms were ranked according to our PPN symptom score. Vitamin B(6) (60 mg/day) was randomly prescribed to 14 of them, and vitamin B(12) (500 microg/day) was prescribed to the others. After 4 weeks, all the patients were re-examined.. We found that predialysis serum P5P levels of HD patients with PPN were not significantly lower than those of matched HD patients without PPN. Nonetheless, it was demonstrated that supplementation with vitamin B(6) for 4 weeks significantly increased the predialysis level of P5P and dramatically attenuated PPN symptoms compared with initial symptoms. No improvement was observed in response to vitamin B(12) supplementation.. This result suggests that although vitamin B(6) deficiency could not be demonstrated in patients with chronic renal failure on high-flux HD, vitamin B(6) supplementation was effective in improving PPN symptoms of various aetiologies, possibly because of vitamin B(6) resistance to PPN in these patients.

Topics: Chronic Disease; Diabetic Neuropathies; Erythropoietin; Female; Glomerulonephritis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Polyneuropathies; Pyridoxal Phosphate; Pyridoxine; Recombinant Proteins; Renal Dialysis; Vitamin B 12

Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy.. Folic acid supplementation is only partially efficacious in correcting moderate elevation of plasma total homocysteine (tHcy) concentrations observed in hemodialysis (HD) patients. Experimental and clinical data have suggested that this partial efficacy may be due to impairment of folic acid metabolism to 5-methyltetrahydrofolate (MTHF) and of MTHF transmembrane transport as well. To bypass these difficulties, we assessed the efficacy of intravenous (i.v.) folinic acid, a ready precursor of MTHF, on reducing plasma tHcy concentrations in HD patients.. In a cohort of 37 patients on intermittent HD treatment, plasma tHcy concentrations were determined before and during i.v. supplementation of folinic acid (50 mg once per week), together with i.v. pyridoxine (250 mg 3 times per week), to prevent vitamin deficiency, particularly in those treated by recombinant erythropoietin.. Folinic acid and pyridoxine i.v. supplementation was given for 11.2 +/- 2.45 months (range 7.5 to 17 months). The mean plasma tHcy levels decreased significantly from 37. 3 +/- 5.8 microM at baseline to 12.3 +/- 5.4 microM on folinic acid treatment (P < 0.001). Moreover, 29 of the 37 patients (78%) had normal plasma tHcy levels at the end of follow-up (that is, <14.1 microM, mean 9.8 microM, range 6.2 to 13 microM). No adverse effects attributable to folinic acid treatment were observed during this time.. Intravenous folinic acid therapy (50 mg) once per week associated with pyridoxine supplementation appears to be an effective and safe strategy to normalize plasma tHcy levels in the majority of chronic HD patients.

Topics: Adult; Aged; Erythrocytes; Female; Humans; Hyperhomocysteinemia; Injections, Intravenous; Kidney Failure, Chronic; Leucovorin; Male; Middle Aged; Pyridoxine; Renal Dialysis; Tetrahydrofolates; Vitamin B 12

Topics: Erythropoietin; Folic Acid; Humans; Kidney Failure, Chronic; Radioimmunoassay; Renal Dialysis; Time Factors; Vitamin B 12

The handling of low, middle and high molecular weight markers was examined in seven stable dialysis patients during hemofiltration with different membranes. Four membranes were examined in a randomized, crossover order (polysulfone, polyamide, AN69 polyacrylonitrile, Asahi polyacrylonitrile) by measuring plasma and dialysate concentrations of phosphate, creatinine, vitamin B12, beta 2-microglobulin, furanic acid, hippuric acid, retinol-binding protein, alpha-1-antitrypsin, and albumin. Sieving coefficients and plasma clearances of beta 2-microglobulin or retinol-binding protein were markedly or slightly lower during hemofiltration with the Asahi polyacrylonitrile membrane than with the other membranes (highest removal with polysulfone/AN69 polyacrylonitrile membranes). No differences of obvious clinical relevance could be seen between the four membranes. A high beta 2-microglobulin removal rate might be important to prevent dialysis-associated amyloidosis.

Topics: Aged; beta 2-Microglobulin; Creatinine; Dialysis Solutions; Hemofiltration; Hippurates; Humans; Kidney Failure, Chronic; Membranes, Artificial; Middle Aged; Molecular Weight; Phosphates; Random Allocation; Renal Dialysis; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Serum Albumin; Vitamin B 12

Topics: Clinical Trials as Topic; Humans; Kidney Failure, Chronic; Kidneys, Artificial; Membranes, Artificial; Microscopy, Electron, Scanning; Sodium Chloride; Ultrafiltration; Uric Acid; Vitamin B 12

Cobalamin is an essential molecule for humans; it is exceptionally important for various body functions, including deoxyribonucleic acid synthesis and cellular energy production. Vegans are more vulnerable to vitamin B12 deficiency than natives with moderate consumption of animal dietary supplements or people with inadequate nutritional patterns. However, the long-term effects of sub-medical deficiency have not been thoroughly studied, but they may have a negative impact on the cardiovascular system, pregnancy outcomes, and vascular, renal, cognitive, bone, and eye health. Alongside the statin remedy, that is a powerful approach for CVD prevention. Another approach is related to the B nutrition substitution remedy with folic acid, and vitamins B6 and B12 are extensively practised nowadays. There is a tremendous interest in plasma homocysteine (tHcy) as a cardiovascular hazard factor. However, current research in the field of its prevention is more inclined toward confirming the benefit of tHcy-reducing remedy with vitamin B12. Thus, while folic acid fortification is primarily aimed at reducing neural-tube defects, it may also play a significant role in the primary prevention of CVD by lowering tHcy. Folate and B-vitamins play important roles in CVD prevention and nutrition policy implementation. Patients affected with Chronic Kidney Disease (CKD) or end-stage Stage Renal Disease (ESRD) experience a tremendous cardiovascular threat that may also further lead to death. As a result, routine monitoring of vitamin B12 levels is likely to be beneficial for the early detection and treatment of metabolic vitamin B12 deficiency, as well as the prevention of heart-related diseases.

Topics: Cardiovascular Diseases; Folic Acid; Humans; Kidney; Kidney Failure, Chronic; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

To present the very long-term follow up of patients with cobalamin A (cblA) deficiency.. A retrospective case series of adult (>16 years) patients with molecular or enzymatic diagnosis of cblA deficiency.. We included 23 patients (mean age: 27 ± 7.6 years; mean follow-up: 24.9 ± 7.6 years). Disease onset was mostly pediatric (78% < 1 year, median = 4 months) with acute neurologic deterioration (65%). Eight patients presented with chronic symptoms, and one had an adult-onset mild cblA deficiency. Most of the patients (61%) were initially classified as vitamin B12-unresponsive methylmalonic aciduria (MMA); in vitro B12 responsiveness was subsequently found in all the tested patients (n = 13). Initial management consisted of protein restriction (57%), B12 (17%), or both (26%). The main long-term problems were intellectual disability (39%) and renal failure (30%). However, 56.5% of the patients were living independently. Intellectual disability was equally distributed among the initial treatment groups, while renal failure (moderate and beginning at the age of 38 years) was present in only one out of seven patients initially treated with B12.. We provide a detailed picture of the long-term outcome of a series of adult cblA patients, mostly diagnosed before the enzymatic and molecular era. We confirm that about 35% of the patients do not present acutely, underlining the importance of measuring MMA in any case of unexplained chronic renal failure, intellectual disability, or growth delay. In addition, we describe a patient with a milder adult-onset form. Early B12 supplementation seems to protect from severe renal insufficiency.

Topics: Adult; Amino Acid Metabolism, Inborn Errors; Child; Humans; Intellectual Disability; Kidney Failure, Chronic; Methylmalonic Acid; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Long-term outcome is postulated to be different in isolated methylmalonic aciduria caused by mutations in the MMAA gene (cblA type) compared with methylmalonyl-CoA mutase deficiency (mut), but case definition was previously difficult.. Cross-sectional analysis of data from the European Registry and Network for Intoxication type Metabolic Diseases (Chafea no. December 1, 2010).. Data from 28 cblA and 95 mut patients in most cases confirmed by mutation analysis (including 4 new mutations for cblA and 19 new mutations for mut). Metabolic crisis is the predominant symptom leading to diagnosis in both groups. Biochemical disturbances during the first crisis were similar in both groups, as well as the age at diagnosis. Z scores of body height and body weight were similar in both groups at birth, but were significantly lower in the mut group at the time of last visit. Glomerular filtration rate was significantly higher in cblA; and as a consequence, chronic renal failure and related complications were significantly less frequent and renal function could be preserved even in older patients. Neurological complications were predominantly found in the mut subgroup. Methylmalonic acidemia (MMA) levels in urine and plasma were significantly lower in cblA. 27/28 cblA patients were reported to be responsive to cobalamin, only 86% of cblA patients were treated with i.m. hydroxocobalamin. In total, 73% of cblA and 98% of mut patients followed a calculated diet with amino acid supplements in 27% (cblA) and 69% (mut). During the study interval, six patients from the mut group died, while all cblA patients survived.. Although similar at first, cblA patients respond to hydroxocobalamin treatment, subsequently show significantly lower levels of MMA and a milder course than mut patients.

Topics: Amino Acid Metabolism, Inborn Errors; Child; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Metabolism, Inborn Errors; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Mitochondrial Membrane Transport Proteins; Mutation; Vitamin B 12

A new extracorporeal circuit for hemodialysis was designed with the goal of improving the middle and high molecular weight toxins removal. A recirculation pathway was added to the hemodialysis circuit and relevant pressure regulation was performed along the circuit in order to keep the ultrafiltration rate as zero. The influence of increasing the recirculation to dialysate flow rate ratio on the removal of urea, vitamin B12, and hemoglobin was investigated. This removal was also modeled by an analytical method and solved by MATLAB software. A significant increase in removal of vitamin B12 (34%) and especially hemoglobin (228%) was achieved using the recirculation flow in an adjusted hemodialysis circuit. The model showed an acceptable agreement with the experimental results which shows its applicability for prediction of different toxin removal in this circuit.

Topics: Dialysis Solutions; Equipment Design; Hemodiafiltration; Hemoglobins; Humans; Kidney Failure, Chronic; Models, Chemical; Molecular Weight; Toxins, Biological; Urea; Vitamin B 12

MMA is associated with chronic tubulointerstitial nephritis and a progressive decline in GFR. Optimal management of these children is uncertain. Our objectives were to document the pre-, peri-, and post-transplant course of all children with MMA who underwent liver or combined liver-kidney transplant in our centers.. Retrospective chart review of all cases of MMA who underwent organ transplantation over the last 10 years.. MMA is a complex metabolic disorder. Renal disease can continue to progress post-liver transplant and close follow-up is warranted. More research is needed to clarify best screening GFR method in patients with MMA. Whether liver transplant alone, continued protein restriction, or the addition of antioxidants post-transplant can halt the progression of renal disease remains unclear.

Topics: Amino Acid Metabolism, Inborn Errors; Carnitine; Child; Child, Preschool; Creatinine; Cystatin C; Disease Progression; Female; Glomerular Filtration Rate; Humans; Infant; Infant, Newborn; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Nephritis, Interstitial; Postoperative Complications; Renal Dialysis; Retrospective Studies; Ubiquinone; Vitamin B 12; Vitamin E

Methylmalonic acidemia (MMA) is an autosomal recessive disorder that can be classified into two types: (1) vitamin B12-responsive and (2) vitamin B12-non-responsive. In MMA cases with long-term survival, renal failure is often a problem, and timing for kidney transplantation for MMA is controversial. We encountered a vitamin B12-non-responsive MMA case for which regular hemodialysis for renal failure was initiated; the patient was 16 years old when she first received regular hemodialysis and 35 years old when she developed pulmonary artery hypertension (PAH). PAH can complicate regular hemodialysis; however, PAH in this case was considered to be a complication of MMA because it was responsive to medical treatment and reversible. In this report, we discuss the role of regular hemodialysis in MMA and the causal relationship between MMA and regular hemodialysis for PAH.

Topics: Adult; Amino Acid Metabolism, Inborn Errors; Female; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Renal Insufficiency; Vitamin B 12

Topics: Female; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Male; Vitamin B 12

Hyperhomocysteinemia (hyperHcy) is an important risk factor for atherosclerosis, which is currently a major cause of death in renal transplant patients (RTRs). The aim of this study was to determine the associated factors of hyperHcy in RTRs in northern Iran.. In 148 stable RTRs, total serum homocysteine (tHcy) level, folate, serum albumin and creatinine, creatinine clearance, lipid status, body mass index (BMI), and blood cyclosporine levels (C0 and C2) were determined. The mean doses of cyclosporine A (mg/kg/day) were recorded.. In this analytic cross-sectional study the prevalence of hyperHcy was 70.3%. Hyperhomocysteinemia was defined as total serum homocysteine of 12 μmol/L or greater. The comparison of the group of 44 patients with tHcy level less than 12 and the group of 104 patients with tHcy level of 12 μmol/L or greater revealed that those subjects with hyperHcy were mostly younger, male, with lower BMI, history of glomerulonephritis, higher serum level of uric acid, and blood cyclosporine trough level (C0) and used higher doses of cyclosporine A. Significant correlation was found between tHcy level and recipients age, serum creatinine, BUN, folate concentrations, and creatinine clearance. However, multivariate analysis indicated that serum folate (P=0.01), vitamin B12 (P=0.05), creatinine (P=0.03), and BUN (P=0.05), and blood cyclosporine trough level (C0, P=0.005) were independently associated with tHcy levels.. HyperHcy persists after successful kidney transplantation in the majority of RTRs. Serum creatinine, BUN, folate and vitamin B12, and blood cyclosporine trough level (C0) are independently associated with tHcy levels.

Topics: Adult; Biomarkers; Blood Urea Nitrogen; Chi-Square Distribution; Creatinine; Cross-Sectional Studies; Cyclosporine; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Immunosuppressive Agents; Iran; Kidney Failure, Chronic; Kidney Transplantation; Linear Models; Male; Middle Aged; Multivariate Analysis; Prevalence; Risk Factors; Time Factors; Vitamin B 12

Topics: Female; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Male; Vitamin B 12

Helicobacter pylori (HP) is a common infection worldwide and has been associated with severe morbidity. The level of vitamin B 12 in HP-infected chronic kidney disease (CKD) patients is reported to be lower than in the general population. The present study has been designed to evaluate the vitamin B 12 level in HP-infected CKD patients. We assessed the serum levels of vitamin B 12 in 50 CKD patients with positive HP serology, one and three months after the eradication of HP infection. There were significant differences between the serum levels of vitamin B 12 in the study patients before (806.98 ± 466.82) and after (760.36 ± 433.93) eradication treatment (P <0.001). We conclude that our study suggests the correlation between vitamin B 12 deficiency in CKD patients and the HP infection status.

Topics: Female; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Male; Middle Aged; Single-Blind Method; Vitamin B 12

Chronic renal failure is a well-known long-term complication of methylmalonic aciduria (MMA-uria), occurring even under apparently optimal metabolic management. The onset of renal dysfunction seems to be dependent on the type of defect and vitamin B12-responsiveness. We report on a patient with a vitamin B12-responsive cobalamin A type (cblA) MMA-uria caused by a homozygous stop mutation (p.R145X) in the cobalamin A gene (MMAA). She was diagnosed with chronic kidney disease (CKD) stage III at the age of 12 years. Following re-evaluation, the patient received vitamin B12 (hydroxocobalamin) treatment, resulting in a significant decrease in the concentration of methylmalonic acid (MMA) in urine and plasma. Until age 29 years glomerular filtration rate remained stable probably due to hydroxocobalamin treatment slowing down progression to end-stage renal failure. Kidney biopsies showed non-specific manifestations of chronic interstitial inflammation. The patient received a renal transplant at age 35 years. Under continuous treatment with hydroxocobalamin there is no evidence of kidney damage due to MMA-uria until the last follow-up 6 years after transplantation. This case report illustrates (i) a long-term follow-up of a patient with MMA-uria due to cblA deficiency, (ii) the involvement of the kidney as a target organ and (iii) the importance of early and adequate vitamin B12 substitution in responsive patients. Further investigation will be necessary to prove the protective effect of hydroxocobalamin in the kidney in vitamin B12-responsive patients.

Topics: Amino Acid Metabolism, Inborn Errors; Child; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hydroxocobalamin; Kidney Failure, Chronic; Kidney Transplantation; Mitochondrial Membrane Transport Proteins; Mutation; Vitamin B 12

Homocysteine (Hcy) is an intermediate in sulfur amino acid metabolism and may induce oxidative stress. Several studies have reported that elevated Hcy in end-stage renal failure may contribute to cardiovascular disease (CVD). The purpose of this study is to investigate whether the changes in Hcy levels correlate better with the CVD outcomes than baseline Hcy level.. A total of 187 patients on dialysis participated in the present prospective observational study and were followed up for 107 months. Baseline cross-sectional analysis of the relationship between Hcy and several factors related to its metabolism was performed, along with survival analysis for the occurrence of CVD. All subjects were divided into the Increase or Decrease of Hcy group on the basis of changes in Hcy from baseline to year 3.. The occurrence of CVD was higher in the Increase (30.1%) than in the Decrease group (9.0%). Greater change of Hcy was associated with risk of CVD (hazard ratio: 3.658) after adjusting basic factors and nutritional status. In stepwise multiple analyses, serum folate, vitamin B(12), cysteine, creatinine, and body mass index were considered to be independent predictors of Hcy.. These data show that increase in Hcy is a powerful predictor of the occurrence of CVD in patients on dialysis.

Topics: Body Mass Index; Cardiovascular Diseases; Creatinine; Cross-Sectional Studies; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Middle Aged; Prospective Studies; Renal Dialysis; Vitamin B 12

The aim of this retrospective cohort study was to identify early risk factors of mortality and develop a mortality risk stratification instrument for severely anaemic Jehovah's Witness patients. It has been shown that Jehovah's Witness patients with the Auckland Anaemia Mortality Risk Score (Auckland AMRS) of 0 to 3 had 4% mortality, Auckland AMRS 4 to 5 32%, Auckland AMRS 6 to 7 50% and Auckland AMRS 8 and above 83%. It is concluded that the Auckland AMRS predicts mortality of severely anaemic Jehovah's Witness patients.

Topics: Adolescent; Adult; Aged; Anemia; Cardiovascular Diseases; Erythropoietin; Factor VIIa; Female; Filgrastim; Folic Acid; Granulocyte Colony-Stimulating Factor; Hemorrhage; Hospital Mortality; Hospitals, Public; Humans; Infections; Iron; Jehovah's Witnesses; Kidney Failure, Chronic; Male; Middle Aged; New Zealand; Plasma; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors; Vitamin B 12; Young Adult

Unexplained macrocytic anemia was common in our hemodialysis (HD) unit. Vitamin B12 requirements may be higher in HD patients; therefore, patients may be deficient despite "normal" serum levels. We studied vitamin B12 status and the effect of parenteral vitamin B12 administration in macrocytic HD patients. A normocytic group was included for comparison.. Prospective cohort study of 62 HD patients (34 macrocytic, 28 normocytic) from November 2008 to March 2009. Patients were on stable doses of darbepoetin and iron replete. Vitamin B12 1,000 µg IV was given once weekly for 4 weeks and follow-up was 12 weeks. Methylmalonic acid (MMA) level was used as an indicator of vitamin B12 status. MCV and hemoglobin were also examined for an effect of B12 administration.. At baseline: all patients had serum B12 levels > 200 pmol/l; 97% had serum folate levels > 55 nmol/l; there was no difference in serum B12 levels between groups (504 vs. 571 pmol/l, p = 0.18); MMA was higher in the macrocytic group (0.56 vs. 0.48 µmol/l, p = 0.048) and hemoglobin (Hg) was lower (119 vs. 125 g/l, p = 0.03); median darbepoetin dose was equivalent (20 µg/week). Following IV vitamin B12, the macrocytic group had a greater and more sustained reduction in MMA (-0.064 vs. -0.0066 µmol/l/wk, p = 0.004). There was no improvement in hemoglobin (Hg), reticulocyte count or MCV in either group. Median darbepoetin dose was unchanged.. IV vitamin B12 led to a sustained decline in MMA levels in macrocytic patients, suggesting functional vitamin B12 deficiency at baseline. However, there were no significant changes in Hg or darbepoetin dose.

Topics: Aged; Aged, 80 and over; Anemia, Macrocytic; Biomarkers; Chi-Square Distribution; Erythrocyte Indices; Female; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Methylmalonic Acid; Middle Aged; Prospective Studies; Renal Dialysis; Statistics, Nonparametric; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

To evaluate the determinants of total plasma homocysteine levels and their relations with nutritional parameters, inflammatory status, and traditional risk factors for cardiovascular disease in renal failure patients on dialysis treatment.. The study was conducted on 70 clinically stable patients, 50 of them on hemodialysis (70% men; 55.3 ± 14.5 years) and 20 on peritoneal dialysis (50% men; 62 ± 13.7 years). Patients were analyzed in terms of biochemical parameters (serum lipids, creatinine, homocysteine [Hcy], creatine-kinase [Ck], folic acid, and vitamin B(12)), anthropometric data, markers of inflammatory status (tumor necrosis factor-alpha, C-reactive protein, interleukin-6), and adapted subjective global assessment.. The total prevalence of hyperhomocysteinemia (>15 μmol/L) was 85.7%. Plasma folic acid and plasma vitamin B(12) were within the normal range. Multiple regression analysis (r(2) = 0.20) revealed that the determinants of total Hcy were type of dialysis, creatinine, Ck, folic acid, and total cholesterol. Hcy was positively correlated with albumin and creatinine and negatively correlated with total cholesterol, high density lipoprotein cholesterol, folic acid, and vitamin B(12).. The determinants of total Hcy in the study sample were type of dialysis, creatinine, Ck, folic acid, and total cholesterol. Evidently, the small sample size might have had an effect on the statistical analyses and further studies are needed. However, Hcy in patients on dialysis treatment may not have the same effect as observed in the general population. In this respect, the association between malnutrition and inflammation may be a confounding factor in the determination of the true relationship between Hcy, nutritional status, and cardiovascular risk factors in this group.

Topics: Adult; Aged; Biomarkers; Brazil; C-Reactive Protein; Creatine Kinase; Creatinine; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Hyperhomocysteinemia; Inflammation; Interleukin-6; Kidney Failure, Chronic; Linear Models; Lipids; Male; Malnutrition; Middle Aged; Peritoneal Dialysis; Prevalence; Renal Dialysis; Risk Factors; Tumor Necrosis Factor-alpha; Vitamin B 12

To study atherogenesis markers in patients with stage 5D chronic kidney disease (CKD-5D) on hemodialysis to determine which parameters are modified and whether their behavior differ between male and female patients of similar age. Total cholesterol, triglycerides, glucose, total proteins, HDL-cholesterol, LDL-cholesterol, oxidative modification of low-density lipoprotein-cholesterol, autoantibodies against oxidized low-density lipoproteins-cholesterol, homocysteine (Hcy), folate, and vitamin B12 were measured in male and female controls and CKD-5D patients on hemodialysis for >6 months. The CKD-5D patients had significantly lower cholesterol, LDL-c and ox-LDL levels and significantly higher ox-LDL-AB and Hcy levels versus their respective controls. The reduction in ox-LDL in CKD patients does not imply a lower risk of atherosclerosis. In fact, the risk may be higher due to a greater capture of ox-LDL by macrophage scavenger receptors, which are increased in these patients. Elevated Hcy levels may also be a risk factor for atherosclerosis in male and female CKD-5D patients.

Topics: Aged; Atherosclerosis; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Lipids; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Risk Assessment; Risk Factors; Triglycerides; Vitamin B 12

Macrocytosis occurs in chronic hemodialysis (CHD) patients; however, its significance is unknown. The purpose of this study was to establish the prevalence and distribution of macrocytosis, to identify its clinical associations and to determine if macrocytosis is associated with mortality in stable, chronic hemodialysis patients.. We conducted a single-centre prospective cohort study of 150 stable, adult CHD patients followed for nine months. Macrocytosis was defined as a mean corpuscular volume (MCV) > 97 fl. We analyzed MCV as a continuous variable, in tertiles and using a cutoff point of 102 fl.. The mean MCV was 99.1 ± 6.4 fl, (range 66-120 fl). MCV was normally distributed. 92 (61%) of patients had an MCV > 97 fl and 45 (30%) > 102 fl. Patients were not B12 or folate deficient in those with available data and three patients with an MCV > 102 fl had hypothyroidism. In a logistic regression analysis, an MCV > 102 fl was associated with a higher Charlson-Age Comorbidity Index (CACI) and higher ratios of darbepoetin alfa to hemoglobin (Hb), [(weekly darbepoetin alfa dose in micrograms per kg body weight / Hb in g/L)*1000]. There were 23 deaths at nine months in this study. Unadjusted MCV > 102 fl was associated with mortality (HR 3.24, 95% CI 1.42-7.39, P = 0.005). Adjusting for the CACI, an MCV > 102 fl was still associated with mortality (HR 2.47, 95% CI 1.07-5.71, P = 0.035).. Macrocytosis may be associated with mortality in stable, chronic hemodialysis patients. Future studies will need to be conducted to confirm this finding.

Topics: Age Factors; Aged; Aged, 80 and over; Comorbidity; Darbepoetin alfa; Erythrocyte Indices; Erythrocytes, Abnormal; Erythropoietin; Female; Folic Acid; Hematinics; Hemoglobins; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; ROC Curve; Thyrotropin; Vitamin B 12

Vitamin status and role in end stage renal disease (ESRD) is controversial. This study was aimed at assessing vitamin A, E, B12, and folic acid status in Tunisian ESRD patients and testing their predictive value for overall mortality and cardiovascular events (CVE).. We examined plasma vitamin A, E, B12, and folic acid in 115 ESRD patients and looked for any correlation with all-cause mortality and CVE after a six year follow-up. Vitamin A and E were determined by HPLC and vitamin B12 and folic acid were determined by enzyme immunoassay.. At enrolment, plasma vitamin A was higher in patients than controls, while plasma vitamin B12 was higher in HD patients. No significant differences were observed for plasma vitamin E and folic acid concentrations between patients and controls. Folic acid and vitamin B12 levels were higher in supplemented patients. During the follow-up period, 17 patients were lost, 15 died, and 36 presented a CVE. Survival analysis showed that mortality and/or CVE trend to be lower for high folic acid levels (Log Rank = 0.098). Cox's regression analysis showed that high levels of folic acid are inversely related to all-cause mortality and/or CVE [Hazard ratio (95% confidence interval), 0.255 (0.08 - 0.740); p = 0.012].. Plasma vitamins A, E, B12, and folic acid concentrations are usually normal in Tunisian ESRD patients. High folic acid levels are associated with fewer CVE and better survival. However, as uremia could be associated with functional vitamin deficiency, maintaining high plasma vitamin levels by adequate nutrition and tolerable supplementation would be beneficial in ESRD patients.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Cause of Death; Comorbidity; Female; Folic Acid; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Prognosis; Proportional Hazards Models; Smoking; Tunisia; Vitamin A; Vitamin B 12; Vitamin E; Young Adult

Genetic polymorphisms that are found among factors of the coagulation cascade are factor V leiden mutation (FVL), prothrombin (PT), and methylenetetrahydrofolate reductase (MTHFR), reported for thrombotic complications. We have investigated the associations of these gene polymorphisms in patients with end-stage renal disease (ESRD).. We genotyped 258 patients for FV G1691A, PT G20210A, and MTHFR (C677T, A1298C) gene by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and were compared with 569 healthy controls. Serum folate, total homocysteine (tHcys), and vitamin B(12) were measured in both patients with ESRD and controls.. No homozygous individuals for the mutant AA genotype of FVL G1691A were observed in this study. The frequency of the heterozygous genotypes was (11.2%), which was nearly 3 times higher than that observed in controls (3.2%), with a odds ratio of 3.87 (P = .0001, 95% CI = 2.11-7.11). PT G20210A mutation was missing in both patients and the controls. At MTHFR locus, TT genotype of C677T was present in 9.6% among ESRD, while CC genotype of A1298C was present in 11.7% of the ESRD. In control group, it was significantly low that is, 4.2% and 3.2%, respectively (P = .0034; OR = 2.44, 95% CI = 1.36-4.36 and P < .0001; OR = 4.03; 95% CI = 2.2-7.37). The combined analysis of the 2 genotypes showed further increased risk in ESRD ~15 folds. Further, the carrier of TT and CC genotypes of C677T and A1298C had significantly higher total homocysteine (tHcys) level than those with CC and AA genotypes (P < .001).. The carrier of FVL, TT genotype of C677T, and CC genotype of A1298C polymorphisms may act as risk factors for ESRD.

Topics: 3' Untranslated Regions; Adult; Alleles; Amino Acid Substitution; Factor V; Female; Folic Acid; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation, Missense; Point Mutation; Prothrombin; Risk Factors; Thrombophilia; Vitamin B 12; Young Adult

We investigated the dietary intake and biochemical status of B vitamins (thiamin, riboflavin, vitamin B6, and vitamin B12) in a group of mainly unsupplemented children with endstage renal disease receiving dialysis, to determine if B vitamin supplementation is indicated.. This was a cross-sectional, observational clinical trial.. Children with endstage renal disease were receiving dialysis, under the care of Renal Services, at Starship Children's Health (Grafton, Auckland, New Zealand).. We studied 12 children (including 7 girls, and 8 children receiving peritoneal dialysis) mean age 7.8 +/- 5.3 years (SD).. Three-day diet records were collected and analyzed with FoodWorks software. Blood was collected for vitamin assay testing.. Dietary intake of B vitamins was measured as a percentage of recommended dietary intake (RDI) or adequate intakes (AIs) for age. Biochemical status was measured as the concentration of each B vitamin compared with reference ranges.. Mean intakes from diet alone comprised <100% of the RDI or AI for each B vitamin. Mean intakes, with nutritional support, reached >100% of the RDI or AI for each B vitamin. All children achieved >100% RDI or AI for thiamin, riboflavin, and vitamin B12. Two children who were not receiving nutritional support received <100% of the RDI for vitamin B6. Blood levels of B vitamins were normal to high, compared with reference ranges, for each B vitamin in all children, indicating adequate status.. Intakes were adequate in the majority of children. Status was adequate in all children. In this group of children undergoing dialysis, B-vitamin supplementation was not indicated.

Topics: Adolescent; Child; Child, Preschool; Cross-Sectional Studies; Diet; Dietary Supplements; Female; Humans; Infant; Kidney Failure, Chronic; Male; Nutritional Status; Peritoneal Dialysis; Riboflavin; Thiamine; Vitamin B 12; Vitamin B Complex

This study sought to determine nutrition-related cardiovascular risk factors in hemodialysis patients.. This was a cross-sectional study.. This study included outpatients from the Hemodialysis Unit of Baskent University Ankara Hospital.. This study was conducted on 93 endstage chronic renal-failure patients (50 male and 43 female) aged between 18 and 65 years. Patients undergoing hemodialysis three times weekly with 4 hours of standardized bicarbonate hemodialysis were included. Patients with cardiovascular disease were excluded.. A questionnaire was administered to patients regarding demographic and disease information. The nutritional status of patients was determined by a food-frequency questionnaire, a 3-day, 24-hour dietary record, and subjective global assessment. Several biochemical parameters were analyzed, and body weight was measured.. Percentages of patients' serum total cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol/low-density lipoprotein cholesterol levels that were higher than National Kidney Foundation (NKF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) criteria amounted to 7.5%, 4.3%, 43%, and 10.8%, respectively. The percentage of patients' serum high-density lipoprotein cholesterol levels that were lower than NKF and NCEP/ATP III criteria reached 41.9%. According to serum albumin levels, 44.1% of patients were malnourished. In terms of patients' dietary total fat intake, 98.9% were higher than NKF and NCEP/ATP III criteria, and all patients' dietary saturated fatty acids intake were higher than recommended. For 87.1% of patients, the dietary polyunsaturated fatty acids/saturated fatty acids ratio was <1. Moreover, in terms of NKF recommendations, the percentages of patients with insufficient dietary folate and vitamin B(12) intake reached 100% and 61.3%, respectively.. Hemodialysis patients should be considered at high risk for developing cardiovascular disease. Therefore, when planning diets of endstage renal disease patients, it is important to consider nutrition-related cardiovascular-disease risk factors for the sake of quality of life and survival.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Cholesterol, HDL; Cross-Sectional Studies; Diet; Dietary Fats; Female; Folic Acid; Humans; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Nutritional Status; Renal Dialysis; Risk Factors; Serum Albumin; Surveys and Questionnaires; Vitamin B 12

Homocysteine is considered as independent predictor of cardiovascular risk. Patients treated with haemodialysis (HD) exhibit elevated homocysteine levels, even four times higher than the general population does. This study focuses on the determination of the vascular risk in patients treated with conventional HD and haemodiafiltration on-line (HDF). It was also considered important to determine whether there was a relationship between homocysteine and the variables given to the patient such as dialysis dose, obesity and treatment with folic acid, vitamin B6 and vitamin B12. A one-year cross-sectional observational study was conducted on patients initially treated with renal replacement therapy such as HDF on-line and conventional HD. Data collected included patient's age, sex, aetiology, duration of dialysis treatment and association with dialysis session, including data on body mass index, waist circumference, treatment with vitamin B6, B12 and folic acid. The results obtained conclusively indicate that patients treated with renal replacement therapy such as HDF on-line exhibit lower homocysteine levels than those treated with conventional HD. Therefore we can conclude that: homocysteine markers indicate that patients treated with HDF on-line are exposed to lower average vascular risk.

Topics: Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Cross-Sectional Studies; Female; Folic Acid; Hemodiafiltration; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Obesity; Online Systems; Renal Dialysis; Risk Assessment; Risk Factors; Treatment Outcome; Vitamin B 12

Cancer incidence and genomic damage of peripheral lymphocytes are elevated in patients with end-stage renal failure. Among other uraemic toxins, homocysteine (Hcy) levels are increased in most of these patients. In healthy individuals, plasma Hcy correlates with the degree of genomic damage observed in peripheral blood lymphocytes (PBL). The accumulation of Hcy can be reduced by supplementation with folic acid and vitamin B12. The aim of this study was to analyse whether this supplementation can also lower the genomic damage in PBL of haemodialysis patients. This may ultimately help to reduce cancer incidence in renal patients.. In a prospective study with 27 patients, we analysed the genomic damage in dialysis patients before and at different time points after the initiation of folate/vitamin B12 supplementation. Genomic damage was measured by the frequency of micronuclei, a subset of chromosomal aberrations, in PBL.. Supplementation with folic acid and vitamin B12 (more markedly with both) reduced the micronucleus frequency in PBL of dialysis patients. This was not mediated by altered lymphocyte proliferation capacity or changes in DNA cytosine-methylation. Plasma-Hcy was lowered more efficiently by the combined folic acid/vitamin B12 supplementation, and lymphocyte DNA of this group exhibited a nonsignificant trend for a reduction of 1,N(6)-etheno-2'-deoxyadenosine, a marker for oxidative stress.. A reduction of the genomic damage in PBL can be achieved in dialysis patients by supplementation with folic acid and vitamin B12. This may be mediated by Hcy reduction.

Topics: Aged; Aged, 80 and over; Case-Control Studies; DNA Damage; Female; Folic Acid; Genome, Human; Homocysteine; Humans; Kidney Failure, Chronic; Lymphocytes; Male; Micronucleus Tests; Middle Aged; Neoplasms; Prospective Studies; Renal Dialysis; Vitamin B 12

Isolated methylmalonic acidurias comprise a heterogeneous group of inborn errors of metabolism caused by defects of methylmalonyl-CoA mutase (MCM) (mut0, mut-) or deficient synthesis of its cofactor 5'-deoxyadenosylcobalamin (AdoCbl) (cblA, cblB). The aim of this study was to compare the long-term outcome in patients from these four enzymatic subgroups. Eighty-three patients with isolated methylmalonic acidurias (age 7-33 y) born between 1971 and 1997 were enzymatically characterized and prospectively followed to evaluate the long-term outcome (median follow-up period, 18 y). Patients with mut0 (n = 42), mut- (n = 10), cblA (n = 20), and cblB (n = 11) defects were included into the study. Thirty patients (37%) died, and 26 patients survived with a severe or moderate neurologic handicap (31%), whereas 27 patients (32%) remained neurologically uncompromised. Chronic renal failure (CRF) was found most frequently in mut0 (61%) and cblB patients (66%), and was predicted by the urinary excretion of methylmalonic acid (MMA) before CRF. Overall, patients with mut0 and cblB defects had an earlier onset of symptoms, a higher frequency of complications and deaths, and a more pronounced urinary excretion of MMA than those with mut- and cblA defects. In addition, long-term outcome was dependent on the age cohort and cobalamin responsiveness.

Topics: Adolescent; Adult; Age of Onset; Alkyl and Aryl Transferases; Amino Acid Metabolism, Inborn Errors; Child; Cobamides; Disease Progression; Female; Follow-Up Studies; Gastrointestinal Diseases; Genetic Predisposition to Disease; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Membrane Transport Proteins; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Mitochondrial Membrane Transport Proteins; Mitochondrial Proteins; Mutation; Nervous System Diseases; Prognosis; Prospective Studies; Time Factors; Vitamin B 12; Vitamin B Complex

The purpose of this study was to evaluate if there was a significant difference in serum and RBC folate or serum cobalamin levels in depressed and nondepressed subjects on hemodialysis (HD).. A cross-sectional design was used in this study. Each subject's serum folate and cobalamin, and red blood cell (RBC) folate were measured. The Beck Depression Index II (BDI-II) was used to assess for depression. Subjects with scores of 10 or greater were considered depressed. Other laboratory, anthropometric, and demographic data were obtained from the subjects' medical records. To assess for significant differences (P < 0.05) in the laboratory values of the outcome variables between depressed and nondepressed subjects, t tests were performed on the groups' mean values.. The study was conducted with patients in two dialysis centers in Texas.. Seventy-three individuals undergoing HD for at least six months who met study inclusion criteria were solicited to participate in the study after the study was approved by the respective institutional review board.. Depression and mental status of each subject were assessed using the BDI-II and the Folstein Mini-Mental State Exam, respectively.. Serum folate, cobalamin, total homocysteine, and RBC folate were measured and mean values were evaluated for significant differences in the depressed and nondepressed groups.. Of the subjects in this study, 43.8% had BDI-II scores > 10 indicating depression. The nondepressed subjects had significantly higher mean serum folate (281 +/- 649 vs. 52 +/- 137 ng/mL), serum cobalamin (1162 +/- 1014 vs. 757 +/- 463 pg/mL), and RBC folate (1433 +/- 1757 vs. 810 +/- 654 ng/mL) levels than did depressed subjects. In the nondepressed group, 39% of subjects were taking a supplement containing 35-42 mg folacin and 7 mg cobalamin per week while only 9.1% of depressed subjects were taking a vitamin containing these levels of B vitamins. The group means were not significantly different for age, months on HD, body mass index, erythropoietin/kg body weight, total homocysteine, hemoglobin, albumin, or ferritin.. As with the general population, lower serum folate, RBC folate, and serum cobalamin levels were found in depressed as compared to nondepressed subjects on HD. Plasma levels of these vitamins may be one of many factors related to depression, but larger studies with stronger designs are needed to confirm the results of this study.

Topics: Biomarkers; Cross-Sectional Studies; Depression; Erythrocytes; Female; Folic Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Psychometrics; Renal Dialysis; Vitamin B 12; Vitamin B Complex

Renal tubular dysfunction and chronic renal failure are well recognised complications of methylmalonic acidaemia (MMA) and can occur even in the context of optimal medical metabolic management. Organ transplantation, such as renal and combined liver and renal transplants, have been utilised in the past for children whose disease cannot be managed by conservative medical practices and those with end stage renal disease. Our patient was diagnosed with B(12)-responsive MMA (subsequently proven to be cblA-type MMA) in the postoperative period following renal transplantation for idiopathic chronic renal failure. She remains well, with excellent graft function and metabolic control 4 years after transplantation. This patient highlights the importance of testing for the inborn errors of metabolism in patients presenting with recurrent acidosis and progressive renal impairment.

Topics: Adolescent; Cobamides; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Metabolism, Inborn Errors; Methylmalonic Acid; Vitamin B 12

Hyperhomocysteinemia, a risk factor for cardiovascular disease, is present in the majority of patients with chronic kidney disease (CKD). Several studies indicated that the moiety of homocysteine (Hcy) with an unbound -SH group (reduced Hcy [rHcy]) is the atherogenic molecule. This study is designed to examine the relation between different forms of Hcy and other aminothiols in hemodialysis (HD) patients, peritoneal dialysis (PD) patients, and nondialyzed patients with CKD.. rHcy, free Hcy (fHcy), and total Hcy (tHcy), as well as different forms of cysteine, cysteinyl-glycine, and glutathione, were studied by using a high-performance liquid chromatography technique in 19 HD patients, 12 PD patients, 47 patients with CKD, and 15 control subjects.. In PD patients, tHcy levels were 2.8 times greater compared with controls, and in HD patients and those with CKD, 2.1 and 1.9 times greater, respectively. Mean rHcy/tHcy ratios were significantly greater in both HD (P < 0.05) and PD patients (P < 0.01), but did not differ in patients with CKD compared with controls. The decrease in rHcy levels during 1 HD treatment was smaller than that in tHcy and fHcy levels, and rHcy/tHcy ratio increased (before HD, 1.25% +/- 0.44%; after HD, 1.44% +/- 0.66%; P < 0.05).. Levels of rHcy and other aminothiols are markedly increased in patients with impaired renal function. In dialysis patients, rHcy/tHcy ratio is markedly elevated and shows greater variability than in patients with CKD and controls. We conclude that because rHcy is believed to induce endothelial dysfunction and may be part of the accelerated atherogenic process in patients with CKD, plasma rHcy level could be a more relevant marker of cardiovascular disease risk than tHcy level.

Topics: Adult; Aged; Atherosclerosis; Biomarkers; C-Reactive Protein; Chronic Disease; Cysteine; Dipeptides; Female; Folic Acid; Glutathione; Hemodiafiltration; Homocysteine; Humans; Hyperhomocysteinemia; Kidney; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Oxidation-Reduction; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Vitamin B 12

This cross-sectional study aimed to investigate the prevalence of hyperhomocysteinemia, the determinants of plasma total homocysteine concentrations, and the relationship of total homocysteine with nutritional parameters in a sample of patients with chronic kidney disease (CKD) and not yet on dialysis. The study was done with outpatients from the Nephrology Division of the Federal University of São Paulo and Oswaldo Ramos Foundation. Sixty-six patients with CKD (70% male; age 58.6+/-15.6 years [mean+/-standard deviation]) with moderate to severe renal impairment (creatinine clearance=29.8+/-14.3 mL/min [0.5+/-0.24 mL/sec]), clinically stable, and older than 18 years were included. A group of 20 healthy subjects from the clinic staff was also studied for reference values for plasma homocysteine, folate, and vitamin B-12 concentration. Fasting blood samples were collected to determine plasma total homocysteine, folate, vitamin B-12, and creatinine. To calculate creatinine clearance, a 24-hour urine collection sample was obtained. The assessment of nutritional status included anthropometric parameters. Pearson correlation, Mann-Whitney test, and multiple linear regression analysis were used for statistical analyses. The main results showed that the concentration of total homocysteine in the patients was significantly increased compared with the healthy subjects (3.4+/-1.7 vs 1.41+/-0.42 mg/L [25.4+/-12.2 vs 10.4+/-3.1 micromol/L]; P<0.001). Plasma folate and plasma vitamin B-12 were in the normal range and did not differ between patients and healthy individuals. A high prevalence of hyperhomocysteinemia (total homocysteine >1.89 mg/L [14 micromol/L]) was found in the patients (89%). Plasma total homocysteine did not correlate with any of the nutritional parameters studied and did not differ between patients in terms of whether they were using or not using folic acid supplementation (3.07+/-1.09 vs 3.55+/-1.78 mg/L [22.7+/-8.1 vs 26.3+/-13.2 micromol/L]; P=0.47), although plasma folate was significantly higher in the supplemented group (12.6+/-3.0 vs 8.0+/-3.6 ng/mL [28.5+/-6.8 nmol/L vs 18.1+/-8.2 nmol/L]; P<0.001). According to the multiple regression analysis, the determinants of total homocysteine were only plasma folate, plasma vitamin B-12, and creatinine clearance (r2=0.20). In conclusion, a high prevalence of hyperhomocysteinemia was found in our sample of nondialyzed patients with CKD. The determinants of total homocysteine levels were plasma folate,

Topics: Anthropometry; Case-Control Studies; Creatinine; Cross-Sectional Studies; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Kidney Function Tests; Linear Models; Male; Middle Aged; Nutrition Assessment; Nutritional Status; Prevalence; Vitamin B 12

A moderate increase in plasma total homocysteine (t-hcy) is considered to be an independent risk factor for cardiovascular disease (CVD) in general population. One of the mechanisms by which hyperhomocysteinemia contributes to cardiovascular risk has been explained to be the increased thrombotic potential. Elevated t-hcy levels were also reported in chronic renal failure patients because the renal function is a major determinant of serum t-hcy levels.. We measured serum hcy and ADP-induced platelet aggregation and plasma tissue factor as a major activator of the coagulation cascade in hemodialysis (HD), peritoneal dialysis (PD) and early stage chronic renal failure (early stage CRF) patients who are not receiving dialysis and compared with those of control. In addition, we also determined serum vitamin B12 and folat levels which are the important factors regulating the metabolism of t-hcy.. Hcy levels in all patient groups were significantly higher (HD: 20.42 +/- 1.91 micromol/l, PD: 35.47 +/- 6.30, early stage CRF: 24.39 +/- 3.06) than the normal levels (10.74 +/- 0.74) in spite of standard multivitamin supplementation. The highest t-hcy values were found in peritoneal dialysis patients. Vitamin B12 levels in hemodialysis/peritoneal dialysis patients and folat levels in hemodialysis/early stage CRF patients were also significantly above those of control. On the other hand, the significant elevations in plasma tissue factor concentration were found in all patient groups (HD: 331.4 +/- 31.3 pg/ml, PD: 306.0 +/- 30.0, early stage CRF: 277.2 +/- 25.5 and. 69.5 +/- 13.5). t-hcy levels were positively correlated with creatinine (r: 0.791 p < 0.002) and tissue factor levels (r: 0.526 p < 0.05) in only early stage CRF group. The association between t-hcy and tissue factor persisted after these two parameters were adjusted for creatinine (r: 0.649 p < 0.05). On the other hand the same correlations were not observed in dialysis patient groups. In spite of the high tissue factor levels, ADP-induced platelet aggregations were found to be lower in all patient groups (HD: 102.6 +/- 6.7, PD: 98.6 +/- 7.6 and Early stage CRF: 84.9 +/- 7.6) than controls (154.9 +/- 13.7).. These results suggest that hyperhomocysteinemia and increased tissue factor level are present in patients with renal failure, despite supplementation with vitamin B6 and B12 and folat. However, elevated levels of these thrombogenic factors are not linked with platelet aggregation.

Topics: Adult; Case-Control Studies; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Platelet Aggregation; Renal Dialysis; Thromboplastin; Vitamin B 12; Vitamin B 6

The homocysteine hypothesis states that circulating homocysteine is a vascular toxin in concentrations that occur in the general population and in renal failure. This hypothesis is currently being tested in the Kidney and End State Renal Disease Study (HOST), but data have emerged since the HOST began that suggest its results will be inconclusive. The crucial treatment component in the HOST is folic acid, but its effect is likely to be lost because the American food supply is now fortified with folic acid. A second concern is that the very high doses of folic acid and pyridoxine being used in the HOST may confound the results. Finally, confounding due to 'reverse epidemiology' was not considered when the HOST was designed. Parenteral vitamin B(12) is a highly promising therapy for homocysteine reduction in end-stage renal disease that merits careful investigation. Clinical trials using it to test the homocysteine hypothesis will avoid the problems inherent in the HOST.

Topics: Clinical Trials as Topic; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Vitamin B 12

Topics: Aged; Brain; Humans; Kidney Failure, Chronic; Magnetic Resonance Imaging; Male; Neural Conduction; Spinal Cord; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinemia is observed in >80% of hemodialysis patients and is considered a risk factor for cardiovascular disease. Vitamin treatment lowers total homocysteine (tHcy) concentrations in plasma and may therefore reduce the associated risk. Current treatment strategies have not achieved normalization of tHcy in the majority of dialysis patients.. We administered folic acid (5 mg) plus vitamin B(6) (50 mg) and B(12) (0.7 mg) intravenously to 38 hyperhomocysteinemic patients (tHcy >18 micromol/L) after each dialysis treatment. The treatment phase lasted 1 month, and serum concentrations of tHcy, methylmalonic acid (MMA), and cystathionine were measured at weeks 0, 2, 4, 6, 8, and 24.. The median serum tHcy concentration decreased significantly, from 26.1 micromol/L at baseline to 13.2 micromol/L at week 4. The median change in tHcy after 4 weeks was 13.4 micromol/L (-51%) compared with baseline. Serum MMA and cystathionine concentrations were reduced by 28% and 26%, respectively, but neither was normalized at 4 weeks. Backward-elimination stepwise regression analysis revealed that higher concentrations of tHcy, MMA, and cystathionine and lower folate at baseline predict changes of tHcy after treatment. Twenty weeks after vitamin withdrawal, tHcy concentrations returned to values comparable to baseline (median, 24.8 micromol/L).. The combination of folic acid, vitamin B(12), and vitamin B(6) used in this study normalized serum concentrations of tHcy in almost all of our hyperhomocysteinemic dialysis patients. This regimen may be used to investigate the effects of homocysteine normalization on cardiovascular outcomes in hemodialysis patients.

Topics: Aged; Aged, 80 and over; Cystathionine; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Male; Methylmalonic Acid; Middle Aged; Renal Dialysis; Vitamin B 12; Vitamin B 6

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.

Topics: Adult; Aged; Cells, Cultured; Cystathionine; Female; Homocysteine; Humans; Kidney Failure, Chronic; Leukocytes, Mononuclear; Male; Methylmalonic Acid; Middle Aged; Vitamin B 12

Serum concentrations of homocysteine (Hcy) and methylmalonic acid (MMA) become increased in B12-deficient subjects and are therefore, considered specific markers of B12 deficiency. Serum level of holotranscobalamin (holoTC) becomes decreased before the development of the metabolic dysfunction. We investigated the usefulness of holoTC in diagnosing B12 deficiency in some clinical settings. We measured serum concentrations of holoTC, MMA, Hcy and total B12 in omnivores, vegetarians, elderly people and haemodialysis patients. Our results indicated that the incidence of holoTC <35 pmol/L was highest in the vegans (76%). Low holoTC and elevated MMA were detected in 64% of the vegans and 43% of the lacto- and lacto-ovovegetarians. An elevated MMA and a low holoTC were found in subjects with total serum B12 as high as 300 pmol/L. The distribution of holoTC in elderly people was similar to that in younger adults (median holoTC 55 pmol/L in both groups). A low holoTC and an elevated MMA were found in 16% of the elderly group. An elevated MMA and a normal holoTC were found in 20% of the elderly group who had a relatively high median serum concentration of creatinine (106.1 micromol/L). Serum concentrations of holoTC in dialysis patients were considerably higher than all other groups (median 100 pmol/L). This was also associated with severely increased serum levels of MMA (median 987 nmol/L). From these results it can be concluded that serum concentration of holoTC is a much better predictor of B12 status than total B12. This was particularly evident in case of dietary B12 deficiency. Serum concentrations of holoTC as well as MMA can be affected by renal dysfunction. Elevated MMA and normal holoTC in patients with renal insufficiency may not exclude vitamin B12 deficiency. HoloTC seems not to be a promising marker in predicting B12 status in renal patients.

Topics: Adult; Age Factors; Aged; Biomarkers; Female; Humans; Kidney Failure, Chronic; Male; Methylmalonic Acid; Middle Aged; Nutritional Status; Renal Dialysis; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Diabetic nephropathy is a common complication in patients with type 2 diabetes that may increase atherothrombotic risk. Hyperhomocysteinemia (HHcy) further increases the risk in those patients. We studied concentrations of total homocysteine (tHcy) and its related metabolites S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) in relation to B-vitamin status and renal function in patients with type 2 diabetes who developed diabetic nephropathy.. The study included 93 patients with renal failure and type 2 diabetes. Chronic kidney disease was classified into four subgroups according to the National Kidney Foundation based on glomerular filtration rate plus pathologic abnormalities or markers of kidney damage.. Serum or plasma concentrations of the metabolites increased significantly with worsening of renal function, whereas serum concentrations of the B vitamins (folate, vitamins B12 and B6) did not differ appreciably between the groups. Moreover, plasma concentrations of AdoHcy and AdoMet were markedly increased in patients with kidney failure compared with those in stage 2 (median AdoHcy, 112.7 vs 10.5 nmol/L; median AdoMet, 162.0 vs 80.0 nmol/L). The AdoMet/AdoHcy ratio was more than 80% lower in patients with renal failure compared with stage 2. Vitamin B12 was a significant determinant of concentrations of AdoMet, tHcy, methylmalonic acid (MMA), and cystathionine.. Increased plasma concentrations of tHcy and methionine cycle intermediates (AdoMet, AdoHcy) are related to disturbed renal function in patients with type 2 diabetes. Vitamin B12 and/or folate are significant predictors of tHcy, cystathionine, MMA, and AdoMet. The effect of therapeutic doses of the B vitamins on AdoMet, AdoHcy, and their ratio should be tested in renal patients.

Topics: Aged; Cystathionine; Cysteine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Folic Acid; Homocysteine; Humans; Kidney; Kidney Failure, Chronic; Male; Methionine; Methylmalonic Acid; Middle Aged; S-Adenosylhomocysteine; S-Adenosylmethionine; Transcobalamins; Vitamin B 12; Vitamin B 6

Unlike iron therapy, folate use is not a standard of care in hemodialysis (HD) patients. Despite iron repletion, poor response to erythropoietin (EPO) treatment is common. Theoretical evidence for folate deficiency (FD) includes chronic blood loss, inflammation, malnutrition, and nutrient loss during dialysis. Due to poor diagnostic standards, early studies failed to establish a role for FD in EPO resistance. Given that hematological response to therapeutic intervention is the gold standard for FD, its diagnosis was therefore based on composite scoring of RBC and/or folate indices. Fifteen subjects (8-20 years) on chronic HD were enrolled in this study. No folate supplement was given in the first six months. Thereafter, 5-mg folic acid was administered orally after HD sessions over a six-month period. Folate indices before and after treatment were compared using percentage differences and paired t-tests. After folate use, the mean Hb increased by 11.4%, while MCV and RDW were reduced. Similarly, 4 of the 15 subjects each had a > or = 20% rise in Hb and a > or = 5% reduction in MCV, while 46.7% had a > or = 2.5% reduction in RDW. Mean RBC folate increased by 24%, while FD scores reduced from 3.8+/-1.2 to 0.4+/-0.7, and the EPO requirement by 90%. In contrast to previous studies, 26.7% of study subjects met the criteria for FD. Furthermore, the substantial (post-folate) reduction in the EPO requirement validates the need for therapeutic intervention, and therefore the presence of functional FD in the population.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Child; Drug Resistance; Erythropoietin; Female; Folic Acid; Folic Acid Deficiency; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Vitamin B 12

To examine the effect of hemodialysis on plasma homocysteine levels, and the relationship of these values to clinical cardiovascular events in patients with end-stage renal disease (ESRD).. Adults undergoing chronic hemodialysis were studied at baseline and at six months. Their clinical histories were obtained at the baseline visit, and measurements of plasma homocysteine concentration were made immediately prior to and following routine dialysis. The occurrence of clinical cardiovascular events was assessed over six months.. We enrolled 147 patients (85 men and 62 women, age 58 +/- 15 years) who required hemodialysis for 3.4 +/- 3.4 years (mean +/- SD). The median homocysteine level for this population (including both pre- and post-dialysis values) was 17.3 micromoles/L. Mean pre-dialysis plasma homocysteine levels of patients with clinical cardiovascular disease did not differ significantly from those without the disease (22.5 +/- 9.9 vs. 25.4 +/- 24.5 micromoles/L, respectively), nor did post-dialysis levels differ between these populations. During six months follow-up, rates of ischemic events were not related to hyperhomocysteinemia. The difference between mean pre- and post-dialysis homocysteine levels (26.3 +/- 19.7 and 15.6 +/- 11.4 micromoles/L, respectively) and the decline in homocysteine over the course of a single dialysis treatment session (10.3 +/- 10.2 micromoles/L) were highly significant (p<0.0005).. Plasma homocysteine levels were elevated in 82% of 147 patients with ESRD and fell to the normal range in a majority of patients during a single dialysis treatment session. Mean pre-dialysis levels did not change significantly over six months, however, and plasma homocysteine levels did not predict cardiovascular events in this population. There was also a trend towards worse outcomes in patients with lower homocysteine levels, which correlates to findings from recent studies. Further studies are needed to clarify the association between hyperhomocysteinemia and coronary risk in patients with ESRD.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Risk Factors; Statistics, Nonparametric; Vitamin B 12

Homocysteine is an independent risk factor for cardiovascular disease in the general population. In addition, it plays a main role in the development of atherogenesis and thrombosis, particularly in end-stage renal disease patients. Therefore, hemodialysis patients are under the burden of homocysteine toxic effects, present in nearly 90% of dialysis patients. Our group found that folic acid is an efficient therapeutic approach to decrease homocysteine levels, and the addition of intravenous methylcobalamin potentiates this effect; however, methylcobalamin alone was unsuccessful to normalize homocysteine levels. With time a group of patients required a higher dose of folic acid to reduce hyperhomocysteinemia. Patients homozygous and, to a lesser extent heterozygous, to the C677T thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) presented a reduced catalytic activity and required a higher folic acid dose. Vascular-access thrombotic events were similar in all patients according to the variants of the enzyme, suggesting that treating hyperhomocysteinemia was the key to lower the risk of thromboses. Noteworthy, hypohomocysteinemia, generally acompanying malnourishment, is associated to higher mortality. Albeit hyper-homocysteinemia is considered a vascular risk factor in renal failure patients, it has not yet been established in this population if its correction is associated with a decrease in the rate of vascular disease and thrombosis. However, given the mentioned evidence about the low risk and good tolerance of vitamin therapy, we believe it useful to know folate, cobalamin and homocysteine blood levels in chronic renal patients and start a prompt treatment, which may proof adequate to maintain homocysteine levels of 10 +/- 5 micromol/l.

Topics: Atherosclerosis; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Methylenetetrahydrofolate Reductase (NADPH2); Renal Dialysis; Risk Factors; Thrombosis; Vitamin B 12; Vitamin B Complex

Helicobacter pylori has been identified as a possible cause of vitamin B12 deficiency in the general population. We assessed any potential relationship between low cyanocobalamin serum levels and Helicobacter pylori status in hemodialysis patients and subsequently correlated these results with the existence of anemia (a common complication in hemodialysis patients), and macrocytosis.. In 29 chronic hemodialysis patients, active H. pylori infection was diagnosed using two different methods regardless of digestive symptoms: by searching for bacterial antigens in stools and by the detection of urea breakdown through breath testing. If these results were non-coincident, gastroscopy was performed and antral biopsies obtained. Patients were subsequently divided into group A (H. pylori-positive, n = 8, 28%) and group B (H. pylori-negative, n = 21, 72%). The corresponding initial values of erythrocytic folic acid, vitamin B12 and homocysteine prior to the first hemodialysis session of each patient were retrospectively collected.. Vitamin B12 levels (normal 200- 900 pg/ml) were significantly lower in group A compared to group B (225.4 +/- 111.9 vs. 707.9 +/- 258.3 pg/ml, p < 0.011). In group A, 5 patients (63%) had vitamin B12 deficiency (154 +/- 24.6 pg/ml). Baseline hematocrits, erythrocyte folic acid and serum homocysteine levels were not different between the groups, but mean corpuscular volumes were significantly higher in group A compared to group B (109.7 +/-14.1 vs. 91.8 +/- 8.8 fl, p = 0.002).. H. pylori-positive chronic hemodialysis patients may present with lower vitamin B12 blood levels and macrocytosis. H. pylori infection should be suspected in this population when low or low-normal vitamin B12 levels or macrocytosis exist.

Topics: Anemia, Macrocytic; Female; Folic Acid; Helicobacter Infections; Helicobacter pylori; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prevalence; Renal Dialysis; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

End-stage renal disease (ESRD) is associated with moderately severe hyperhomocysteinemia that is incompletely normalized by oral folic acid therapy and vitamin B12.. We administered 1 mg hydroxocobalamin parenterally at 14-day intervals to vitamin B12-replete hemodialysis patients who were already consuming 6 mg folic acid daily by mouth. Plasma total homocysteine (tHcy), serum folate, vitamin B12 and methylmalonate were measured immediately before and after 4 and 8 weeks of therapy.. Serum folate concentrations were consistently over 25 times the upper normal limit. Hydroxocobalamin therapy increased serum vitamin B12 concentrations 14-fold (p < 0.001) and reduced plasma tHcy by 23% from 29.7 +/- 2.9 to 22.8 +/- 2.5 micromol/L (p < 0.01); serum methylmalonate decreased by one-third (p < 0.05).. These results demonstrate the Hcy-lowering potential of parenteral vitamin B12 in folic acid supplemented vitamin B12-replete hemodialysis patients, and indicate the need for formal dose-optimization studies of this simple, inexpensive and promising approach to Hcy reduction in end-stage renal disease.

Topics: Administration, Oral; Aged; Folic Acid; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Methylmalonic Acid; Middle Aged; Parenteral Nutrition; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

The association of variants of the gene encoding methionine synthase reductase (MTRR) with hyperhomocysteinemia, folate and Vitamin B(12) status in kidney graft recipients is unknown. We examined two mutations in MTRR in a cross-sectional study of 733 kidney graft recipients. The allele frequency of MTRR 66G was 0.55. 369 patients (50.3%) were heterozygous and 219 patients (29.9%) were homozygous for the mutation. None of the patients showed the 997C > G mutation. The allelic variants of MTRR 66A > G showed no significant association with total homocysteine (tHcy) levels, both in univariate analyses, and in a multivariate model controlling for age, gender, body mass index, renal function, time since transplantation, underlying kidney disease, as well as the MTHFR 677C > T/1298A > C genotypes. Similarly, no significant associations between the MTRR 66A > Ggenotypes and plasma folate or Vitamin B(12) levels were found. In conclusion, MTRR 66A > G has no major effect on tHcy, folate, or Vitamin B(12) plasma concentrations in kidney graft recipients.

Topics: Adult; Analysis of Variance; Base Sequence; Cross-Sectional Studies; Female; Ferredoxin-NADP Reductase; Folic Acid; Gene Expression; Graft Rejection; Graft Survival; Homocysteine; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Molecular Sequence Data; Multivariate Analysis; Mutation; Polymerase Chain Reaction; Prognosis; Vitamin B 12

Treatment of hyperhomocysteinemia in patients with end-stage renal disease (ESRD) can be performed with the oral application of vitamins. However, this therapy rarely normalizes total homocysteine (tHcy) levels. Frequently, a rebound is observed after the end of treatment. Currently, no data are available about intravenous combination therapy with folic acid, pyridoxine (B6), and cyanocobalamin (B12).. We conducted a prospective pilot study comprising 13 patients on chronic hemodialysis treatment (63.7+/-4.9 years; 6 female, 7 male) for 27 weeks. The patients received 10 mg folic acid and 100 mg pyridoxine intravenously (IV) after each dialysis plus 1000 microg vitamin B12 IV once a week for 9 weeks. Between weeks 10 and 18 the patients received 10 mg folic acid, 100 mg vitamin B6 once a week, and 1000 microg vitamin B12 bimonthly IV.. The therapy regimen decreased tHcy concentration (baseline: 30.5+/-2.2 micromol/L) significantly to 17.4+/-1.2 micromol/L, 15.6+/-1.0 micromol/L, and 16.4+/-0.1 micromol/L after 3, 6, and 9 weeks, respectively (p<0.01 vs. baseline concentration). The maximum reduction (-47.5+/-3.3%) of tHcy concentration was measured after 6 weeks of therapy. During the following maintenance therapy, tHcy-levels did not increase and no rebound of tHcy was detected during follow-up (week 27:16.5+/-1.97 micromol/L).. The concept of a short, high-dose induction therapy with intravenous folic acid, pyridoxine, cyanocobalamin, and a subsequent low-dose maintenance regimen is effective in the treatment of hyperhomocysteinemia in patients with ESRD.

Topics: Aged; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Folic Acid; Follow-Up Studies; Humans; Hyperhomocysteinemia; Infusions, Intravenous; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Pilot Projects; Probability; Prospective Studies; Pyridoxine; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vitamin B 12

The Homocysteine Study (HOST) Veterans Affairs Cooperative Studies Program No. 453, is a prospective, randomized, two arm, double blind study of patients with end stage renal disease (ESRD) or advanced chronic kidney disease (ACKD, defined as an estimated creatinine clearance of 30 ml/min or less). Its primary objective is to determine whether administration of high doses of three vitamins, folic acid, vitamin B6 and vitamin B12, to lower the high plasma homocysteine levels, will reduce all cause mortality. The secondary objectives are to examine whether the treatment lowers the incidence of myocardial infarction, stroke, amputation of a lower extremity, a composite of death and the foregoing three events, the plasma homocysteine level, and, in ESRD patients undergoing hemodialysis, thrombosis of the vascular access. A unique feature of this trial is that after initial evaluation at enrollment and one return visit the follow up is exclusively by phone (or, if necessary, by mail). The subject is contacted every three months throughout the duration of the study from a central location. The study drug is shipped to the patient from a central location rather supplied locally. In a two year enrollment period, 2006 patients are to be enrolled. The duration of the observation period is four to six years. Data will be stored and analyzed at a coordinating center. The study design has the power to detect a reduction in all cause mortality rate of 17%. Issues related to the unique features of the design of this study are discussed.

Topics: Adult; Cause of Death; Double-Blind Method; Folic Acid; Homocysteine; Hospitals, Veterans; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Middle Aged; Multicenter Studies as Topic; Patient Selection; Prospective Studies; Pyridoxine; Randomized Controlled Trials as Topic; Renal Dialysis; Research Design; Treatment Outcome; Vitamin B 12

This study was designed to check whether lowering plasma homocysteine concentration resulting from treatment is associated with decreased thrombotic activity in haemodialyzed patients. The study group included 38 patients undergoing chronic haemodialysis. Blood was collected after an overnight fast after two days of weekend intervals in haemodialysis. Tests were performed before and after eight weeks of combined treatment with vitamin B6 (100 mg/day, oral), vitamin B12 (1 mg s.c. once a week) and folic acid (15 mg/day, oral). Homocysteine, vitamin B12 and folic acid concentrations in serum, antithrombin, fibrinogen and protein C activity in plasma and thromboxane B2 levels in activated platelets were determined before and after treatment. Combined treatment resulted in a statistically significant decrease in plasma homocysteine concentration. No influence of this finding on parameters of thrombotic activity was found. The following conclusions were drawn: (1) Treatment with physiological doses of vitamin B12, B6 and folic acid effectively decreases homocysteine concentration in haemodialyzed patients with chronic renal failure. (2) Monitoring of treatment with concentrations of folic acid and vitamin B12 is unfounded as no significant correlations with homocysteine were revealed. (3) The decrease in homocysteine concentration in haemodialyzed patients does not affect thrombotic activity. Therefore, treatment with physiological vitamin doses should not be recommended for routine use.

Topics: Aged; Dose-Response Relationship, Drug; Female; Folic Acid; Hematologic Tests; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Reference Values; Renal Dialysis; Thrombosis; Treatment Outcome; Vitamin B 12; Vitamin B 6

Hyperhomocysteinemia is well documented in chronic renal failure (CRF) and premature and progressive occlusive vascular disease is common in CRF. The combined effects of renal failure, folate and vitamin B(12) levels, and a common mutation (C677T) in the methylenetetrahydrofolate reductase (MTHFR) gene that leads to total plasma homocysteine (tHcy) elevation in CRF children were investigated. Forty-two children (15 females) with CRF, mean age 10.3+/-4.7 years, were included. The mean glomerular filtration rate (GFR) was 37.3+/-16.9 ml/min per 1.73 m(2). The control group comprised 33 children (18 females) with a mean age of 8.6+/-3.4 years. There were 40% of CRF patients with hyperhomocysteinemia. Folate and vitamin B(12) deficiencies were identified in 14% (n=6) and 5% (n=2), respectively, of all patients. On univariate analysis, the tHcy serum concentration was negatively correlated with the plasma folate concentration (P<0.05) in controls, and with GFR (P<0.05) in patients. On multiple regression analysis for the predictors of tHcy serum concentrations, folic and vitamin B(12 )were significant in controls, whereas only GFR was significant in CRF children. In our patients no effect of the MTHFR polymorphism on tHcy levels was seen This result, in addition to the limited number of patients, may partially be explained by the low prevalence of folate deficiency in our patients.

Topics: Adolescent; Child; Child, Preschool; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Point Mutation; Predictive Value of Tests; Prevalence; Regression Analysis; Vitamin B 12

Transcobalamin II is a serum protein that transports vitamin B12 from the intestine to the tissues. This complex, holo-transcobalamin II, may reflect vitamin B12 availability in the body. Conflicting data exist with regard to the effect of a polymorphism in the gene coding for transcobalamin II, TCN2 776C>G, on transcobalamin II levels in the general population, which in turn may affect holo-transcobalamin II, vitamin B12, as well as total homocysteine (tHcy) plasma levels. The effect of TCN2 776C>G on vitamin B12 cellular availability in dialysis patients is unknown.. We examined the effect of TCN2 776C>G on holo-transcobalamin II, vitamin B12, and tHcy plasma concentrations in 120 dialysis patients.. Holo-transcobalamin II levels were normal or supranormal in all patients and showed a linear association with albumin (r = 0.205, P = 0.025) and with vitamin B12 (r = 0.778, P = 0.001), but not with age, creatinine, body mass index, tHcy, ln-tHcy, vitamin B6, plasma folate, and red blood cell folate concentration. TCN2 776C>G showed no effect on holo-transcobalamin II, vitamin B12, and tHcy concentration [one-way analysis of variance (ANOVA), post-hoc Scheffe test]. Multiple linear regression analyses showed that albumin and B12 are independently associated with holo-transcobalamin II, whereas TCN2 776C>G and MTHFR 677C>T had no effect. Independent predictors of ln-tHcy included creatinine, red blood cell folate, and the MTHFR 677TT genotype. There was also an effect of the TCN2 776CC genotype on ln-tHcy levels in this multivariate analysis, however, that deserves cautious interpretation because there was no effect of TCN2 genotypes by ANOVA and Scheffe test [median ln-tHcy concentrations according to TCN2 genotypes (micromol/L): CC, 3.22; CG, 3.30; GG, 3.23].. TCN2 776C>G does not influence holo-transcobalamin II or vitamin B12 levels, and has no major effect on tHcy concentrations of end-stage renal disease patients.

Topics: Adult; Aged; Biological Availability; Cross-Sectional Studies; Cytosine; Female; Genotype; Guanine; Homocysteine; Humans; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Osmolar Concentration; Transcobalamins; Vitamin B 12

This study was undertaken to evaluate two different doses of folic acid and their effects on the control of hyperhomocysteinemia, and on pro-oxidant and antioxidant changes in a group of 32 hemodialysis (HD) patients. Blood samples were collected in a group of patients at three different times: before (basal; B), after the first (S1), and after the second (S2) three-month supplementation periods, and compared to samples from a group of healthy individuals. Analysis of vitamins (C, E, folate, and B12), oxidant parameters (lipid and protein oxidation), and homocysteine were performed. Hyperhomocysteinemia of different degrees was observed in all patients on HD (45.30 +/- 24.89 microM). Oxidative stress was also detected, with lipoperoxidation and protein oxidation being associated with lower concentrations of antioxidant substances (vitamins E and C). The first folate dose (2.5 mg after each dialysis session) reduced by half the initial concentrations of homocysteine (44.92 +/- 22.05 to 20.56 +/- 6.79 microM; p < 0.05) but did not normalize its values. The second dose (15 mg) did not show an additional effect, but it was at this time that lipoperoxidation was significantly reduced, although the protein oxidation showed no change. It was concluded that the first dose of folic acid was efficient in reducing homocysteine concentrations, without normalization of values. The participation of hyperhomocysteinemia in oxidative stress appeared to be partial, but in combination with dialysis treatment, may contribute to the induction of an oxidative environment in this group. The possible antioxidant action of folate must also be considered in this case, acting directly against lipoperoxidation or through hyperhomocysteinemia control. Routine supplementations of folic acid and other antioxidant vitamins should be considered in hemodialysis in order to reduce homocysteine levels to lower values, that although not normal, may be more beneficial in minimizing the cardiovascular risk in this group.

Topics: Ascorbic Acid; Dietary Supplements; Female; Folic Acid; Hematinics; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Lipid Peroxidation; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Proteins; Renal Dialysis; Vitamin B 12; Vitamin E

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis in adult patients on dialysis or after kidney transplantation. There are few data on homocysteine (Hcy) concentrations in children under these circumstances. The aim of our study was to evaluate plasma Hcy levels and their determining factors in children on renal replacement therapy. In 29 children and adolescents on chronic dialysis therapy and in 34 children after renal transplantation (Tx) fasting total plasma Hcy, red blood cell (RBC) folate, and serum vitamin B(12) levels were measured. The plasma Hcy levels were expressed as number of standard deviations (SD) from mean level in age- and gender-matched controls. In dialysis patients the mean plasma Hcy level was elevated (4.4+/-0.8 SDs), without significant difference between patients on hemodialysis or continuous cycling peritoneal dialysis. In the dialysis patients a negative correlation ( r=-0.49) between plasma Hcy levels and RBC folate concentrations was found. Oral folate supplementation was given to 8 of 21 dialysis patients, resulting in high RBC folate levels (>800 micro g/ml) and normalization of the plasma Hcy levels (0.4+/-0.5 SDs). In Tx patients the mean plasma Hcy level was 5.6+/-1.4 SDs. Multivariate regression analysis revealed that the main factor determining Hcy level after kidney Tx was creatinine clearance. Patients with normal kidney function had a mean Hcy concentration of 1.69+/-0.86 compared with 10.0+/-2.2 in children with decreased function. Folate and cyclosporine levels had less significant effects on Hcy concentrations. Seven patients who were evaluated while on dialysis and after a successful kidney Tx demonstrated a significant reduction in Hcy levels. Children and adolescents on dialysis therapy and with impaired renal function after renal Tx have significant hyperhomocysteinemia. Oral folate supplementation normalizes the increased plasma Hcy levels and should be added to the medical treatment of all children with impaired renal function.

Topics: Adolescent; Adult; Child; Child, Preschool; Erythrocytes; Female; Folic Acid; Humans; Hyperhomocysteinemia; Infant; Kidney Failure, Chronic; Kidney Transplantation; Male; Renal Dialysis; Risk Factors; Vitamin B 12

Hyperhomocysteinemia, a risk factor for vascular disease, is found in children as well as in 80% of adult patients with end-stage renal disease. The aim of this study was to assess the changes in plasma homocysteine concentrations after renal transplantation (RT). Plasma homocysteine, vitamin B(12), and folate concentrations were prospectively measured in six patients at three points, before and post transplantation (6 months, 4 years), and compared with controls using standardized scores (Z score) for each of these parameters. Folic acid supplementation was introduced after the evaluation at 6 months. Patients had elevated median plasma homocysteine Z scores during dialysis (4.12). When assessed at 6 months and 4 years, median plasma homocysteine Z scores were, respectively, 2.35 and 0.29. Median folate Z scores were 1.89 during dialysis, -0.26 at 6 months, and 3.26 at 4 years post RT. Median vitamin B(12) Z score was 2.12 during dialysis, 0.58 at 6 months, and -0.07 at 4 years post RT. Glomerular filtration rate (GFR) improved after RT, with median GFR of 84.5 ml/min per 1.73 m(2) at 6 months. This stabilized to a value of 70.5 ml/min per 1.73 m(2) at 4 years. When comparing values before and after RT at 6 months, changes were observed only for GFR ( P<0.03) and vitamin B(12) ( P<0.05). There were no changes in plasma homocysteine, folate, and serum albumin. At 4 years, a significant decrease in plasma homocysteine was observed ( P<0.05) with increased GFR ( P<0.03). No significant changes were observed in plasma albumin, folate, and vitamin B(12) concentrations. In conclusion, elevated plasma homocysteine in children during dialysis persists after RT despite a significant improvement in renal function. However, normalization was attained when patients were supplemented with folic acid. Further controlled studies are required to evaluate the determinants and treatment of elevated plasma homocysteine in pediatric transplant patients.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Serum Albumin; Vitamin B 12

It is known that hyperhomocystinemia is an independent risk factor for development of atherosclerosis. In end stage renal disease the frequency of hyperhomocystinemia is much greater than in normal populations.. In this study homocystein (Hcy), folic acid and vitamin B12 concentrations were determined in 125 chronic renal failure patients being on folic acid supplementation (3 mg/day). In 107 patients the frequency of C667T polymorphism of methylene tetrahyrofolate reductase (MTHFR) was also determined. The relationships between these parameters were also studied.. It was found that in these patients who are under continuous folic acid supplementation the mean level of homocysteine was 16.8 +/- 7.2 mumol/L, a value considerably lower than the homocysteine concentration reported for non-supplemented patients. The elevation of homocysteine concentrations was independent of gender, time spent in renal replacement therapy, and the type of renal replacement therapy (hemodialysis: 17.6 +/- 12.6; hemodiafiltration: 16.6 +/- 12.9 mumol/L). Data showed an inverse relation between plasma homocysteine concentrations and the concentrations of folic acid and vitamin B12. Moderately severe hyperhomocystinemia (Hcy > 20 mumol/L) was found in about 30% of patients. In those the frequency of patients for homozygous T677 allele of MTHFR was about 25-30%. However, in all ESRD patients the frequency of the homozygotes was the same then in the normal population. Homocysteine plasma levels correlated with MTHFR polymorphism: in the wild type group Hcy was 14 +/- 7 mumol/L, in the heterozygous group was 17.2 +/- 6.2 mumol/L, and in the homozygous group was 21 +/- 19 mumol/L.. Long-term folic acid supplementation decreased the homocysteine level in end stage renal disease patients. However, in folic acid resistant group, who were in 30% homozygotes for C667T of MTHFR (suggesting that homocysteine-methionine remethylation cycle is disturbed), instead of the administration of folic acid, methylene tetrahydrofolate supplementation might be considered.

Topics: Adult; Age Factors; Aged; Female; Folic Acid; Hemodiafiltration; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Renal Dialysis; Time Factors; Vitamin B 12

Cardiovascular disease (CVD) is the principle cause of death in patients with end-stage renal disease. Some gene polymorphisms and hyperhomocysteinemia have been implicated in the pathogenesis of CVD. The aim of this study was to assess the relationships between angiotensin-converting enzyme genotype, endothelial nitric oxide synthase genotype, and methylenetetrahydrofolate reductase (MTHFR) genotype and CVD in patients on hemodialysis and to clarify the determinants of plasma homocysteine level. One hundred and sixty-eight patients on hemodialysis (87 males and 81 females, mean age 60.7 +/- 13.1 years) were included. A history of CVD was present in 25% of the patients. There was a significant difference in the distributions of MTHFR non-VV genotype and MTHFR VV genotype between patients with a CVD history and patients without a CVD history, but no difference in the distributions of angiotensin-converting enzyme genotypes and endothelial nitric oxide synthase genotypes. The plasma homocysteine concentration was significantly higher in patients with MTHFR VV genotype than in patients with MTHFR non-VV genotype. The plasma homocysteine concentration was negatively correlated with plasma vitamin B12 concentration and plasma folate concentration. On stepwise multiple-regression analysis for the predictors of plasma homocysteine concentration, MTHFR VV genotype and gender were significant. In conclusion, MTHFR polymorphism may be a risk factor for CVD in patients on hemodialysis, and MTHFR VV genotype and gender may be strong determinants of the plasma homocysteine level.

Topics: Adult; Aged; Cardiovascular Diseases; Cross-Sectional Studies; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Oxidoreductases Acting on CH-NH Group Donors; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Renal Dialysis; Risk Factors; Statistics as Topic; Vitamin B 12

Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common in dialysis patients and particularly in those homozygous for a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition). B-complex vitamin supplements have been shown to lower plasma total homocysteine (tHcy) concentrations, but the respective effectiveness of folate and oral vitamin B12 is not yet known. Our objectives were: (i) to determine the status of folate and vitamin B12 in a cohort of unsupplemented dialysis patients (ii) to assess the homocysteine-lowering effect of a folate supplement and then of a folate supplement with added vitamin B12. The responses were analysed for the C677T genotypes of MTHFR.. Plasma tHcy, folate and vitamin B12 were measured in 51 haemodialysis patients genotyped for the C677T MTHFR mutation (homozygotes, TT; heterozygotes, CT; without mutation, CC). All patients were then given daily supplements of 15 mg of folic acid for 2 months. They were given daily supplements of 1 mg of vitamin B12 in addition to the folate supplements for a further 2 months. Plasma tHcy, folate and vitamin B12 were monitored after each intervention.. At baseline folate and vitamin B12 deficiencies were found in 10% and 6% of the patients. Initial plasma tHcy concentrations were high in all patients (mean 38.1+/-15 micromol/l). CC patients tended to have a lower tHcy concentration than pooled CT and TT patients. After 2 months of folate therapy, tHcy concentration decreased significantly to 20.2+/-7 micromol/l (P<0.001) and no significant differences were observed between the different genotype subgroups (19.4+/-6 for CC, 21.3+/-8 for CT, 18.5+/-4 for TT). A significant positive relationship was found between the reduction of tHcy and its initial value (rho=0.615, P<0.0001). The impact of the added vitamin B12 was negligible since tHcy concentrations did not change for the patients as a whole (19.8+/-7 micromol/l, NS) or in any subgroup (19.1+/-5 for CC, 20.3+/-9 for CT and 20+/-7 micromol/l for TT).. (i) Folate and vitamin B12 deficiencies were observed in 10% and 6% respectively of our unsupplemented dialysis patients. (ii) After folate therapy, tHcy levels decreased significantly in all patients and were identical between the three C677T MTHFR genotype subgroups. (iii) Vitamin B12 supplements are useful in folate treated patients to prevent cobalamin deficiency and its neurological consequences but they did not lower tHcy plasma levels for the patients as a group or for any of the MTHFR subgroups.

Topics: Administration, Oral; Aged; Cohort Studies; Female; Folic Acid; Folic Acid Deficiency; Genotype; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Prospective Studies; Renal Dialysis; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinemia, a well-recognized cardiovascular risk factor, is frequent in hemodialysis (HD) patients. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C-->T substitution at nucleotide 677, is associated with homocysteine (Hcy) level elevation. We examined whether three factors involved in the methionine cycle could influence plasma Hcy concentrations in HD patients: MTHFR polymorphism; vitamin B12, an essential cofactor; and folate, the substrate. In a cross-sectional study, serum vitamin B12, folate, and plasma Hcy were measured and MTHFR genotyping was performed in 534 HD patients. Effects of MTHFR genotypes, vitamin B12, and folate on plasma Hcy levels were examined in 450 HD patients not administered vitamin B12 or folate. To examine the effect of vitamin B12 on plasma Hcy concentrations, we compared plasma Hcy concentrations in HD patients with and without vitamin B12 supplementation. To examine whether functional vitamin B12 deficiency exists even in HD patients with normal vitamin B12 concentrations, 15 HD patients (serum vitamin B12 concentrations, 250 to 2,100 pg/mL) were treated with vitamin B12 (mecobalamin, 1.5 mg/d) for 8 weeks. Serum concentrations of methylmalonic acid (MMA) and vitamin B12 were measured. Hcy levels were higher and folate levels were lower in patients with the TT and CT genotypes compared with patients with the CC genotype. Analysis of covariance to determine independent predictors of high Hcy levels identified low serum vitamin B12 and folate levels and high albumin (Alb) levels in CC-genotype patients, low folate levels and high Alb levels in CT-genotype patients, and low folate levels in TT-genotype patients. Plasma Hcy levels were lower in CC- and CT-genotype patients with vitamin B12 supplementation than in those without supplementation. Vitamin B12 supplementation for 8 weeks significantly reduced MMA concentrations in HD patients with normal serum vitamin B12 concentrations. These results indicate that MTHFR genotype influences the correlation of Hcy level with vitamin B12 and folate levels in HD patients. Functional vitamin B12 deficiency may exist, even in HD patients with normal vitamin B12 concentrations. The efficacy of vitamin B12 and folate supplementation on plasma Hcy levels may depend on MTHFR genotype.

Topics: Cross-Sectional Studies; Dietary Supplements; Female; Folic Acid; Folic Acid Deficiency; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Methylmalonic Acid; Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Renal Dialysis; Vitamin B 12; Vitamin B 12 Deficiency

Homocysteine is a risk factor for cardiovascular disease. Mutations in a key enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase, may contribute to hyperhomocysteinemia and alter folate and cobalamin levels. After starting hemodialysis, 10 mg oral folate daily and 500 micrograms intravenous methylcobalamin once weekly were prescribed to 27 hemodialysis patients (time on hemodialysis > or = 12 months) and two groups were defined: Group A normal; Group B heterozygous. Initial, third and twelfth month measurements of homocysteine, serum folate and vitamin B12 levels were collected and analyzed. Heterozygous state of methylenetetrahydrofolate reductase prevalence was 48% and homozygozity 4%. Hyperhomocysteinemia was present in both groups. Cobalamin final levels were significantly lower in Group B compared to Group A. Homocysteine, serum folate and cobalamin levels at third and twelfth month were significantly different from baseline levels but non-different between them in both groups. In Group B, vitamin B12 at third month was significantly higher than initial, but final measurements were not different from baseline determinations. In conclusion, the heterozygous prevalence of the enzyme in hemodialysis patients is similar to that reported in the general population; hyperhomocysteinemia is frequent in hemodialysis patients and final levels in heterozygous patients are significantly higher than in normal patients. Cobalamin levels are lower in the heterozygous group. After one year of treatment, homocysteine tends to increase, suggesting a secondary resistance phenomenon to vitamin supplementation in heterozygous patients.

Topics: Adult; Chi-Square Distribution; Female; Folic Acid; Heterozygote; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Point Mutation; Renal Dialysis; Statistics, Nonparametric; Vitamin B 12

Hyperhomocysteinemia is a risk factor for atherosclerosis that is common in chronic renal failure (CRF), but its cause is unknown. Homocysteine metabolism is linked to betaine-homocysteine methyl transferase (BHMT), a zinc metalloenzyme that converts glycine betaine (GB) to N,N dimethylglycine (DMG). DMG is a known feedback inhibitor of BHMT. We postulated that DMG might accumulate in CRF and contribute to hyperhomocysteinemia by inhibiting BHMT activity.. Plasma and urine concentrations of GB and DMG were measured in 33 dialysis patients (15 continuous ambulatory peritoneal dialysis and 18 hemodialysis), 33 patients with CRF, and 33 age-matched controls. Concentrations of fasting plasma total homocysteine (tHcy), red cell and serum folate, vitamins B(6) and B(12), serum zinc, and routine biochemistry were also measured. Groups were compared, and determinants of plasma tHcy were identified by correlations and stepwise linear regression.. Plasma DMG increased as renal function declined and was twofold to threefold elevated in dialysis patients. Plasma GB did not differ between groups. The fractional excretion of GB (FE(GB)) was increased tenfold, and FED(MG) was doubled in CRF patients compared with controls. Plasma tHcy correlated positively with plasma DMG, the plasma DMG:GB ratio, plasma creatinine, and FE(GB) and negatively with serum folate, zinc, and plasma GB. In the multiple regression model, only plasma creatinine, plasma DMG, or the DMG:GB ratio was independent predictors of tHcy.. DMG accumulates in CRF and independently predicts plasma tHcy concentrations. These findings suggest that reduced BHMT activity is important in the pathogenesis of hyperhomocysteinemia in CRF.

Topics: Adult; Aged; Aged, 80 and over; Arteriosclerosis; Betaine; Betaine-Homocysteine S-Methyltransferase; Creatinine; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methyltransferases; Middle Aged; Peritoneal Dialysis; Predictive Value of Tests; Pyridoxine; Renal Dialysis; Sarcosine; Uremia; Vitamin B 12; Zinc

The effect of the combined 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C genotype on total homocysteine (tHcy), folate, and vitamin B(12) plasma levels was investigated in 983 subjects, including 415 hemodialysis patients, 179 peritoneal dialysis patients, and 389 healthy individuals. Mean tHcy plasma concentrations were 27.2 +/- 15.8 micromol/L in hemodialysis patients, 25.4 +/- 19.1 micromol/L in peritoneal dialysis patients, and 8.9 +/- 3.5 micromol/L in healthy individuals. Hyperhomocysteinemia (tHcy > 15 micromol/L) was detected in 81.6% of patients and 2.6% of controls. Multiple stepwise regression analysis showed that the MTHFR 677C-->T/1298A-->C genotype (CC/AA, CC/AC, CC/CC, CT/AA, CT/AC, TT/AA), vitamin use, age, folate and vitamin B(12) plasma level were significant predictors of tHcy plasma levels. Analysis of variance showed that this effect of MTHFR genotypes on tHcy level was caused by significantly greater tHcy levels in 677TT/1298AA hemodialysis and peritoneal dialysis patients versus other genotypes. Compound heterozygous controls (677CT/1298AC genotype) had significantly greater tHcy levels compared with 677CC/1298AA controls. There was no major effect of MTHFR polymorphisms on folate and vitamin B(12) plasma concentrations. This study shows that the MTHFR 677TT/1298AA genotype, but not the 677CT/1298AC genotype, is a significant predictor of tHcy plasma levels in dialysis patients.

Topics: Adult; Aged; Dialysis; Female; Folic Acid; Gene Frequency; Genotype; Homocysteine; Humans; Kidney Failure, Chronic; Linear Models; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Peritoneal Dialysis; Polymorphism, Genetic; Renal Dialysis; Vitamin B 12

Homocysteine (Hcy) has emerged as an important risk factor for atherosclerotic disease. Elevated levels in chronic dialysis patients may contribute to high vascular mortality, but little is known about levels of related amino acids in this group. In an observational study in the clinical setting we sought to document these.. In 114 hemodialysis patients pre-dialysis total plasma homocysteine, vitamin B12 and red blood cell (RBC) folate concentrations were measured. In a subgroup of patients (n = 42), other plasma amino acids were measured pre- and post-dialysis. All patients were routinely taking oral folic acid supplements (1.2 mg per week).. Elevated homocysteine concentrations were found in all patients (geometric mean 33.1 umol/l, range 13.8 - 69.2 umol/l, laboratory reference range (RR) 3-13 umol/l). RBC folate levels were high (1223 +/- 54.5 nmol/l mean +/- SE, RR 300 - 710 nmol/l) and inversely related to pre-dialysis plasma Hcy (r = -0.44, p < 0.001). Hcy levels were not related to vitamin B12 levels. A history of vascular disease was not associated with higher concentrations of Hcy. Hcy clearance on dialysis was substantial (mean Hcy reduction 33 +/- 14%). While plasma methionine levels were normal, serine levels were significantly lower than the reference range (59.3 +/- 2.39 umol/l (mean +/- SE, RR 70 - 195 umol/l)) and directly related to levels of glycine (r = 0.52, p < 0.001). Glycine levels were within normal range. Although overall levels were low, higher serine levels were related to elevated homocysteine (r = 0.42, p < 0.01). Dialytic loss of glycine, serine and methionine was moderate.. An inverse association between RBC folate and homocysteine levels extended to 3 times the upper limit of normal for folate, suggesting a role for high dose folic acid supplementation in the treatment of renal-failure related hyperhomocysteinemia. Low serine levels are expected as it is primarily synthesized in the kidney. The direct relationship between serine and homocysteine is consistent with the reported lack of effect of serine supplements on high Hcy levels.

Topics: Amino Acids; Erythrocytes; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Renal Dialysis; Vitamin B 12

Peritoneal dialysis (PD) patients have been shown to require less erythropoietin as compared with hemodialysis (HD) patients to maintain similar hemoglobin values. In our unit, we observed that diabetic PD patients required less erythropoietin treatment than did other PD patients. We therefore compared the amount of erythropoietin needed in diabetic and non diabetic patients on PD to maintain a similar hemoglobin value. All polycystic patients were excluded from the study because they rarely require erythropoietin. We also excluded patients with bone marrow disease, active gastrointestinal bleeding, or patients very resistant (requiring more than 25,000 U per week) to Eprex (recombinant human erythropoietin: Janssen-Cilag, North York, Ontario, Canada). Patients not requiring Eprex were also excluded from the study. We calculated the weekly erythropoietin dose in the two groups. We also compared hemoglobin level, iron transferrin saturation, vitamin?12 level, and serum folate. Diabetic patients required a lower weekly erythropoietin dose. Diabetic PD patients in our unti receive an average 4497 U per week compared with 7593 U per week for non diabetic PD patients. The difference (approximately 3000 U per week) is statistically significant.

Topics: Diabetes Mellitus; Diabetic Nephropathies; Erythropoietin; Folic Acid; Hemoglobins; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Renal Dialysis; Transferrin; Vitamin B 12

Glomerular filtration is one of the major determinants of plasma total homocysteine (tHcy). To evaluate the respective roles of residual glomerular filtration (by measuring a specific protein marker, cystatin C), genetic polymorphisms and nutritional status in tHcy blood levels in end-stage renal disease patients (ESRD) under hemodialysis and supplemented with folate, we measured tHcy, folate, vitamin B12 (B12), creatinine, cystatin C, albumin and C-reactive protein and determined the polymorphism of methylenetetrahydrofolate reductase (MTHFR) (C677T and A1289C) and of methionine synthase (MS) (A2756G) in 114 ESRD patients before hemodialysis and 76 control subjects. All patients received a folate supplementation of 700 microg/day. Hyperhomocysteinemia was observed in all patients and exceeded the upper normal limit by 2-fold in 52.4% of the patients. Serum folate was significantly increased and the B12 level was not different from controls. Folate, Cystatin C and creatinine were significantly correlated to tHcy, while no correlation was found between tHcy, albumin and C-reactive protein. No difference in genotype frequency between ESRD patients and controls was found for MTHFR A1289C and MS A2756G. The MTHFR 677TT genotype was less frequent and was associated with a significantly higher tHcy level in patients. Folate and residual glomerular filtration estimated by cystatin C and creatinine levels were two independent determinants of tHcy in ESRD patients. These data suggest that hyperhomocysteinemia is a consequence as well as a complicating factor of renal failure.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adult; Creatinine; Cystatin C; Cystatins; Female; Folic Acid; Genotype; Glomerular Filtration Rate; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Renal Dialysis; Vitamin B 12

Mild to moderate hyperhomocysteinemia is very common among patients undergoing haemodialysis. There is sufficient evidence that hyperhomocysteinemia is an independent risk factor for cardiovascular and or atheromatous disease in end stage renal failure patients. Vitamin supplementation such as vitamin B6, B12 or folate has been proposed to correct this metabolic disturbance and it is to be proved if this intervention benefit these patients, but there is no agreement whether oral folate supplementation is capable to normalize homocysteine levels in end stage renal failure patients.. In 53 patients, undergoing haemodialysis, homocysteine levels (Hcy), folate, vitamin B12, ferritin and C-reactive protein (CRP) were estimated before and after dialysis, without folate supplementation. Thirty voluntary blood donors were used as controls to compare homocysteine levels. After four weeks of oral folate supplementation (10 mg/24 hours) the levels of homocysteine, serum folate and intra-erythrocyte folate were estimated again. Eighteen months later the survival rate of our patients was recorded and analyzed in relation to Hcy and CRP levels.. The results showed that haemodialysis patients exhibited, almost, fourfold higher homocysteine levels than controls (27.39 +/- 11.54 vs 7.38 +/- 3.5, t = -8.2, p = 0.000000). Folate levels, vitamin B12 and CRP increase significantly after haemodialysis where as homocysteine levels decrease (Hcy1 vs. Hcy2: z = 2.08, p = 0.03). Fourteen (14) patients suffered from coronary heart disease (CHD) and they exhibited the higher levels of homocysteine (Hcy1 vs. CHD: z = -3.4, p = 0.0006). All estimations performed revealed a negative correlation between homocysteine levels and plasma or intra-erythrocyte folate. No other variable exhibited any significant influence upon homocysteine levels. After folate supplementation homocysteine levels in the whole number of patients were unchanged (Hcy(before) vs. Hcy(after): 27.39 +/- 11.54 vs. 26.95 +/- 8.22, z = 0.3, p = 0.7, NS). When patients with homocysteine levels higher than 24 micromol/L were selected, a significant decrease was observed (34.77 +/- 9.32 vs. 30.0 +/- 8.05, z = 2.09, p = 0.02). Forty-two patients were treated with erythropoietin for their anemia and we found a positive correlation between C-reactive protein levels and rhu-Epo dose (CRP vs. Epo: r = 0.45, p = 0.002). Homocysteine levels did not exhibit any significant influence upon short-term survival (U = -0.37, p = 0.3, NS) where as CRP levels exhibit a significant influence upon short-term survival (U = 2.15, p = 0.005).. Homocysteine levels in haemodialysis patients are fourfold higher than healthy controls. Folate, vitamin B12 and CRP increases significantly after dialysis. Patients with coronary heart disease exhibit the highest levels of homocysteine. The homocysteine levels are inversely related with the folate levels. The exogenous folate supplementation increase the serum folate levels but decreases homocysteine only in patients with higher than mild hyperhomocysteinemia. Hcy doesn't exert any significant effect upon the short-term survival of the haemodialysis patients but CRP level is a god predictor of the short-term survival of these patients.

Topics: Adult; C-Reactive Protein; Case-Control Studies; Coronary Disease; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Vitamin B 12

Aim of the study was to: 1) estimate plasma profile of sulphur AA in children with chronic renal failure (CRF) and in children on hemodialysis (HD), and 2) to evaluate any correlation with serum folic acid (FA) and vitamin B12.. 32 pts with CRF: 9 with GFR > 20 ml/min/1.73 m2 (group 1), 9 with GFR < 20 ml/min/1.73 m2 (group 2), and 14 pts on HD (group 3).. plasma homocysteine (Hcys), methionine (Met), cysteine (Cys), serine (Ser) were measured with gas chromatography. Serum FA and vit. B12 were measured using MEIA method.. median Hcys concentrations were the lowest in group 1: 5 mumol/l vs 9 mumol/l (group 2) and 20 mumol/l (group 3) (p = 0.03). Similarly, the lowest Met levels were observed in group 1--26 mumol/l, vs 66 mumol/l (group 2) and 281 mumol/l (group 3) (p = 0.001). Median Cys level in group 1 was 98 mumol/l vs 54 mumol/l (group 2), and 122 mumol/l (group 3) (p = 0.02). No differences were found in median Ser levels: 153 mumol/l (group 1) vs 239 mumol/l (group 2) and 240 mumol/l (group 3). The median concentrations of FA were 6.3 ng/ml (group 1) vs 8 ng/ml (group 2) and 15 ng/ml (group 3) (NS). Median concentrations of vit. B12 were 256 pg/ml (group 1) vs 379 pg/ml (group 2) and 322 pg/ml (group 3) (NS). There were no correlation between sulphur AA and FA and vit. B12 levels. The only difference between pts with Hcys levels remaining in lower and upper quartile concerned Met concentration (38 vs 263 mumol/l, p < 0.02) and GFR (p < 0.01).. Hyperhomocysteinemia develops already in moderate CRF. In pts on HD levels of Met and Cys are also raised. FA and vit. B12 concentrations are normal and do not correlate with plasma concentrations of sulphur AA.

Topics: Adolescent; Adult; Amino Acids, Sulfur; Child; Folic Acid; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Renal Dialysis; Vitamin B 12

Hyperhomocysteinemia has been increasingly recognized as an important risk factor for elevated atherosclerotic vascular disease in chronic renal failure. We measured in patients with chronic renal failure homocysteine and metabolites of its 2 metabolic pathways, transulfuration (cystathionine, cysteine) and remethylation (methionine, methylmalonic acid, 2-methylcitric acid).. Eleven patients on conservative treatment (creatinine clearance 10 to 30 ml/min) and 50 chronic uremic subjects on regular hemodialysis were included in the study. Twenty-two of the dialysis patients received daily oral multivitamin supplementation containing 10 mg vitamin B6, 6 micrograms vitamin B12, and 1 mg folic acid during the last year before the study started.. In the hemodialysis group homocysteine levels were higher compared with the patients on conservative treatment. Hemodialysis patients with additional vitamin supplementation showed significantly lower homocysteine levels than those without. The pattern of metabolites was different to these results: all metabolites were higher in hemodialysis patients, too (significant for cysteine and methionine), but vitamin supplementation failed to lower all metabolites.. Analysis of metabolites additional to homocysteine levels may help to understand different results in evaluation of atherosclerotic risk of hyperhomocysteinemia in chronic renal failure.

Topics: Adult; Aged; Arteriosclerosis; Cysteine; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Methionine; Middle Aged; Pyridoxine; Renal Dialysis; Severity of Illness Index; Vitamin B 12; Vitamin B Complex

Study the determinants of plasma total homocysteine (tHcy) levels, such as fasting levels of serum creatinine (SCr), albumin, plasma tHcy, folate, B(12), and pyridoxal-5'-phosphate (PLP) in chronic Korean renal transplant recipients (RTR).. Cross-sectional study.. Nephrology & Transplant Service in Catholic University Kangnam St. Mary's Hospital, Seoul, Korea.. Ninety-one chronic Korean RTR with stable renal function who were > or =6 months post-transplant.. Used medical record review and anthropometric measurements, and overnight (10 to 14 hours) fasting blood samples were measured for plasma tHcy, PLP, folate, B(12), SCr, and albumin.. The prevalence of hyperhomocysteinemia (tHcy > 12 micromol/L) was 56%, and 47% had low plasma folate levels (<3 ng/mL). Linear modeling with analysis of covariance adjusted for age, sex, albumin, SCr, and plasma B-vitamin status revealed that only SCr (standard regression coefficient R = +0.663, P<.001), plasma folate (R = -0.276, P =.001), and B(12) (R = -0.149, marginal, P =.08) were independent determinants of fasting tHcy levels in this patient population.. Renal function is the major independent determinant of the fasting tHcy levels among chronic, stable Korean RTR, and that B-vitamin status plays a secondary role among such patients.

Topics: Adult; Aged; Cardiovascular Diseases; Creatinine; Cross-Sectional Studies; Fasting; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Kidney Transplantation; Korea; Male; Middle Aged; Prevalence; Pyridoxal Phosphate; Serum Albumin; Vitamin B 12

Topics: beta 2-Microglobulin; Biocompatible Materials; Evaluation Studies as Topic; Hemodiafiltration; Humans; Kidney Failure, Chronic; Kinetics; Male; Membranes, Artificial; Metabolic Clearance Rate; Models, Biological; Polymethyl Methacrylate; Renal Dialysis; Urea; Vitamin B 12

The type of dialysis membrane used for routine therapy has been recently shown to correlate with the survival of chronic hemodialysis patients. We examined whether this effect of dialysis membrane could be explained by differences in dialyzer removal of middle molecules using data from the 1991 Case Mix Adequacy Study of the United States Renal Data System. The sample analyzed included patients who had been treated by hemodialysis for 1 year or more, who were dialyzed with the 19 most commonly used dialyzers in 1991, and for whom delivered urea Kt/V could be calculated from predialysis and postdialysis blood urea nitrogen concentrations. Vitamin B12 (1,355 daltons) was used as a marker for middle molecules, and the clearance of vitamin B12 was estimated based on in vitro data. After adjustments for case mix, comorbidities, and urea Kt/V, the relative risk of mortality for a 10% higher calculated total cleared volume of vitamin B12 was 0.953 (P < 0.0001 v 1.000). Similar results were obtained when middle molecule removal was adjusted for body size. We conclude that both small and middle molecule removal indices appear to be independently associated with the risk of mortality in chronic hemodialysis patients. Differences in mortality when using different types of dialysis membrane may be explained by differences in middle molecule removal.

Topics: Humans; Kidney Failure, Chronic; Membranes, Artificial; Renal Dialysis; Risk; Survival Analysis; Vitamin B 12

Hyperhomocysteinemia is an independent risk factor for atherosclerotic complications in patients with end-stage renal disease, although the mechanisms remain unclear. The major determinants of plasma homocysteine concentration are usually folate, vitamin B12, pyridoxal 5'-phosphate (vitamin B6), and glomerular filtration rate.. We measured factors, including plasma folate, vitamin B12, vitamin B6, creatinine, as well as the dose and duration of dialysis, that might affect plasma homocysteine concentrations in 130 patients on hemodialysis (HD) and compared these observations with those in 46 patients on peritoneal dialysis (PD). Independent determinants of total homocysteine were identified using a multiple logistical regression analysis.. Total homocysteine values averaged 29.8 mumol/liter in HD patients, significantly higher than the mean value of 19.9 mumol/liter observed in patients on PD (P < 0.001). The prevalence of hyperhomocysteinemia was 90.8% among HD patients, significantly higher than the prevalence of 67.4% among PD patients. Folate values in HD patients averaged 45.5 nmol/liter and were significantly lower than in PD patients (104.2 nmol/liter, P < 0.001). For patients on HD, the only determinant of total homocysteine concentration was plasma folate (r = -0.31, P < 0.001). In contrast, for PD patients, total homocysteine did not correlate with plasma folate, vitamin B12, or vitamin B6.. Hyperhomocysteinemia is more prevalent and intense in HD patients compared with those on PD. The homocysteine response may become refractory to excess folate supplementation in PD patients.

Topics: Creatinine; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Peritoneal Dialysis; Prevalence; Pyridoxine; Renal Dialysis; Smoking; Time Factors; Vitamin B 12

Hyperhomocysteinemia is frequently found in patients with end-stage renal disease (ESRD). Plasma total homocysteine (tHcy) concentrations may be reduced by supplementation with folic acid or combinations of folic acid, vitamin B12, and vitamin B6. Supplementation studies with vitamin B12 alone in patients with ESRD have not yet been published. In this study, we investigated the effects of intravenous injection of cyanocobalamin (1 mg/wk for 4 weeks) in ESRD patients (N = 14) with low serum cobalamin concentrations (<180 pmol/L). All patients had elevated levels of plasma tHcy, methylmalonic acid (MMA), and cystathionine before supplementation. After supplementation, plasma tHcy and MMA decreased 35% and 48%, respectively; however, cystathionine levels were unchanged. The extent of the plasma tHcy reduction tended to be influenced by the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR). Serum cobalamin increased significantly upon supplementation, whereas serum folate levels were substantially reduced by 47%. In contrast, red blood cell (RBC) folate was unchanged. This study shows that vitamin B12 supplementation effectively decreases both MMA and plasma tHcy in ESRD patients with low B12 levels. Furthermore, it illustrates the close interrelation between vitamin B12 and folate metabolism.

Topics: Adult; Aged; Dietary Supplements; Female; Folic Acid; Folic Acid Antagonists; Genotype; Homocysteine; Humans; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Methylmalonic Acid; Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Vitamin B 12

The purpose of this study is to observe the influence of the methylenetetrahydrofolate reductase (MTHFR) gene (677C-->T substitution) on plasma homocysteine levels in end-stage renal disease (ESRD) patients who received a relatively large amount of folate (2 mg/d) and are undergoing hemodialysis. A cross-sectional study of plasma homocysteine, vitamin B(12), and folate was performed in patients with ESRD. The study population for the MTHFR gene study included 312 healthy subjects and 106 patients with ESRD undergoing hemodialysis. The C677T transition in the MTHFR gene was detected by HinF 1 restriction enzyme analysis and subsequent electrophoresis in a 3% agarose gel. The genotype of the MTHFR gene in 106 patients with ESRD was homozygous C677T mutation (VV) in 17 patients (16.1%) and heterozygous (AV) in 63 patients (58.4%); 26 patients (24.5%) did not carry this mutation (AA). The mean levels of homocysteine, vitamin B(12), and folate in the patients with ESRD were 23.3 +/- 14.0 mmol/L, 620.2 +/- 98.5 pmol/L, and 138.6 +/- 55.6 nmol/L, respectively. There was no significant difference in homocysteine levels among the three genotypes: 28.2 +/- 19.4 mmol/L for VV, 22.7 +/- 14.9 mmol/L for AV, and 23.4 +/- 11.1 mmol/L for AA genotype (P > 0.05). There was no difference in genotype distribution between the patient groups of less than 25th and greater than 75th percentiles, classified according to plasma homocysteine levels (P = 0.47). In conclusion, with high-dose folate supplementation, the hyperhomocysteinemia in patients with ESRD does not seem to be caused by the 677C-->T mutation in the MTHFR gene.

Topics: Cross-Sectional Studies; Female; Folic Acid; Gene Frequency; Genotype; Homocysteine; Humans; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Point Mutation; Polymorphism, Genetic; Renal Dialysis; Vitamin B 12

Hyperhomocyst(e)inemia is now recognized as an independent risk factor for atherosclerotic cardiovascular disease in patients with normal renal function. Hyperhomocyst(e)inemia is common in patients with chronic renal failure. This study is designed to look for an association between hyperhomocyst(e)inemia and atherosclerotic vascular disease in patients with end-stage renal disease (ESRD). Two hundred eighteen patients undergoing hemodialysis were enrolled onto the study and had predialysis bloodwork performed for total homocyst(e)ine, red blood cell folate, and vitamin B(12) levels. A history of clinically significant atherosclerotic vascular disease (ischemic heart disease, cerebrovascular disease, or peripheral vascular disease) was elicited by patient questionnaire and verified by careful inpatient and outpatient chart review. Atherosclerotic vascular disease was present in 45.9% of patients. Mean homocyst(e)ine concentration was 26.7 micromol/L (95% confidence interval [CI], 25.0 to 28.4) overall. Mean homocyst(e)ine concentration was 28.6 micromol/L (95% CI, 25.6 to 31.7) and 25.0 micromol/L (95% CI, 23.2 to 26.8) in patients with and without atherosclerotic disease, respectively (P = 0.036). The adjusted odds ratio for atherosclerotic disease was 2.12 (95% CI, 1.03 to 4.39) for those subjects with a homocyst(e)ine level in the highest quartile compared with the lowest 3 quartiles. In the 126 men, the adjusted odds ratio for atherosclerotic disease was 3.4 (95% CI, 1. 24 to 9.42) for those with homocyst(e)ine levels in the highest quartile compared with the lowest 3 quartiles. No association was found between homocyst(e)ine level and atherosclerotic disease in women. In conclusion, there is an association between hyperhomocyst(e)inemia and atherosclerotic vascular disease in patients undergoing dialysis. Prospective studies need to further examine the relationship between homocyst(e)ine level and atherosclerosis in women with ESRD.

Topics: Aged; Arteriosclerosis; Coronary Artery Disease; Cross-Sectional Studies; Erythrocytes; Female; Folic Acid; Homocysteine; Homocystine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Odds Ratio; Renal Dialysis; Retrospective Studies; Risk Factors; Sex Factors; Vitamin B 12

In order to see whether conventional low-dose folic acid supplement along with vitamin B6 and B12 reduces hyperhomocysteinemia in patients with ESRD, we compared the levels of homocysteine, vitamin B6, B12 and folic acid among 3 groups of patients: 44 ESRD patients on hemodialysis with replacement of folic acid, vitamin B6, and B12 (dialysis group); 27 chronic renal failure patients without vitamin replacement (predialysis group); and 17 hypertensive patients without vitamin replacement (control group). Mean plasma total homocysteine concentration was higher in the dialysis (15.5 +/- 6.6 micromol/l) and the predialysis groups (15.7 +/- 4.2 micromol/l) than in the control group (6.2 +/- 1.5 micromol/l) (p < 0.001). However, there was no difference in homocysteine concentrations between the dialysis and predialysis groups. In the control and predialysis groups, the homocysteine concentration showed a reverse correlation with the concentrations of folic acid (r = 0.584, p = 0. 014 for the control group; r = 0.431, p = 0.247 for the predialysis group) and vitamin B12 (r = 0.485, p = 0.049 for the control group; r = -0.562, p = 0.023 for the predialysis group) but not with vitamin B6. In conclusion, plasma folic acid concentrations were 3-4 times higher in the dialysis than in the predialysis group. But these levels of folic acid are not enough to reduce hyperhomocysteinemia in ESRD.

Topics: Adult; Female; Folic Acid; Homocysteine; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Pyridoxine; Renal Dialysis; Vitamin B 12

We previously investigated the factors involved in uraemic neuropathy in patients undergoing regular haemodialysis and found a significant relationship between the severity of vibration sensation impairment and the patients' smoking habits. The administration of methylcobalamin markedly improved the severity of uraemic neuropathy in terms of vibration perception thresholds. We presumed that abnormal cyanide metabolism is involved in the development of uraemic neuropathy.. Serum levels of thiocyanate (SCN-), the detoxication product of cyanide, were determined in 12 patients with preterminal chronic renal failure (PCRF), 30 patients undergoing regular haemodialysis (HD patients), and 13 healthy volunteers as a control group. Nine of the 30 HD patients were smokers. In addition, in 10 HD patients without smoking habits and 10 non-smoking healthy volunteers, the proportion of each vitamin B12 analogue in total vitamin B12 was estimated.. The mean serum SCN- level of the 12 PCRF patients (5.1 +/- 1.5 micrograms/ml) was significantly higher than that of the control (2.8 +/- 0.9 micrograms/ml) (P < 0.01). The mean SCN- level before haemodialysis in the 21 non-smoking HD patients was identical to that in the PCRF group, whereas the level in the nine smoking HD patients (7.2 +/- 1.8 micrograms/ml) significantly higher than that in the non-smoking subgroup (P < 0.01). In 16 HD patients with methylcobalamin treatment, serum SCN- levels were lower than in those without methylcobalamin treatment (4.5 +/- 0.5 micrograms/ml in non-smoking subgroup, P < 0.05). And in the methylcobalamin-treated subgroup (n = 5), the proportion of each vitamin B12 analogue in total vitamin B12 was normal. In the untreated subgroup (n = 5), the proportion of cyanocobalamin fraction (10.5 +/- 2.6%) was as high as the level in Leber's disease patients, while the proportion of methylcobalamin fraction was low. And the serum cyanocobalamin level was higher in the treated subgroup.. In uraemic patients, cyanide detoxication capability is impaired because of a reduced SCN- clearance, and increased cyanocobalamin synthesis indicates elevation of cyanide pool, which would be related to the development of uraemic neuropathy. Methylcobalamin was considered to be utilized in cyanide detoxication process via cyanocobalamin synthesis.

Topics: Adult; Cyanides; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Osmolar Concentration; Renal Dialysis; Thiocyanates; Uremia; Vitamin B 12

There is an excess prevalence of hyperhomocysteinemia in dialysis-dependent end-stage renal disease (ESRD) patients. Cross-sectional studies of the relationship between elevated total homocysteine (tHcy) levels and prevalent cardiovascular disease (CVD) in this patient population suffer from severe methodologic limitations. No prospective investigations examining the association between tHcy levels and the subsequent development of arteriosclerotic CVD outcomes among maintenance dialysis patients have been reported. To assess whether elevated plasma tHcy is an independent risk factor for incident CVD in dialysis-dependent ESRD patients, we studied 73 maintenance peritoneal dialysis or hemodialysis patients who received a baseline examination between March and December 1994, with follow-up through April 1, 1996. We determined the incidence of nonfatal and fatal CVD events, which included all validated coronary heart disease, cerebrovascular disease, and abdominal aortic/lower-extremity arterial disease outcomes. After a median follow-up of 17.0 months, 16 individuals experienced at least one arteriosclerotic CVD event. Cox proportional-hazards regression analyses, unadjusted and individually adjusted for creatinine, albumin, and total cholesterol levels, total/HDL cholesterol ratio, dialysis adequacy/residual renal function, baseline CVD, and the established CVD risk factors (ie, age, sex, smoking, hypertension, diabetes/glucose intolerance, and dyslipidemia) revealed that tHcy levels in the upper quartile (> or = 27.0 mumol/L) versus the lower three quartiles (< 27.0 mumol/L) were associated with relative risk estimates (hazards ratios, with 95% confidence intervals for the occurrence of (pooled) nonfatal and fatal CVD ranging from 3.0 to 4.4; 95% confidence intervals (1.1-8.1) to (1.6-12.2). We conclude that the markedly elevated fasting tHcy levels found in dialysis-dependent ESRD patients may contribute independently to their excess incidence of fatal and nonfatal CVD outcomes.

Topics: Adult; Aged; Arteriosclerosis; Blood Glucose; Cardiovascular Diseases; Cholesterol, HDL; Cohort Studies; Comorbidity; Diabetes Mellitus; Fasting; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Proportional Hazards Models; Prospective Studies; Pyridoxine; Renal Dialysis; Single-Blind Method; Smoking; Treatment Outcome; Vitamin B 12

Limited data are available on the determinants of homocysteinemia or the association between plasma homocysteine (Hcy) levels and prevalent cardiovascular disease (CVD) in maintenance dialysis patients. We assessed etiology of renal failure, residual renal function and dialysis adequacy-related variables, and vitamin status, as determinants of fasting total plasma homocysteine (Hcy) in 75 maintenance dialysis patients. We also assessed the potential interactive effect on plasma Hcy of folate status and a common mutation (ala to val; homozygous val-val frequency approximately 10%) in methylenetetrahydrofolate reductase (MTHFR), a folate-dependent enzyme crucial for the remethylation of homocysteine (Hcy) to methionine. Lastly, we evaluated whether the Hcy levels differed amongst these patients in the presence or absence of prevalent CVD, after adjustment for the traditional CVD risk factors. Fasting total plasma Hcy, folate, pyridoxal 5'-phosphate (PLP; active B6), B12, creatinine, glucose, total and HDL cholesterol levels, and presence of the ala to val MTHFR mutation were determined, and clinical CVD and CVD risk factor prevalence were ascertained. General linear modelling/analysis of covariance revealed: (1) folate status and serum creatinine were the only significant independent predictors of fasting Hcy; (2) there was a significant interaction between presence of the val mutation and folate status, i.e., among patients with plasma folate below the median (< 29.2 ng/ml), geometric mean Hcy levels were 33% greater (29.0 vs. 21.8 microM, P = 0.012) in the pooled homozygotes (val-val) and heterozygotes (ala-val) for the ala to val mutation, vs. normals (ala-ala); (3) there was no association between prevalent CVD and plasma Hcy. Given potentially intractable survivorship effects, prospective cohort studies will be required to clarify the relationship between plasma Hcy or any putative CVD risk factor, and incident CVD in dialysis patients. If a positive association between plasma Hcy and incident CVD can be established in maintenance dialysis patients, the current data provide a rationale for additional folic acid supplementation in this patient population.

Topics: Adult; Aged; Amino Acid Sequence; Cardiovascular Diseases; Cholesterol, HDL; Comorbidity; Creatinine; DNA Mutational Analysis; Female; Folic Acid; Glucose Intolerance; Homocysteine; Humans; Hypertension; Kidney Failure, Chronic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Peritoneal Dialysis; Polymorphism, Restriction Fragment Length; Prevalence; Renal Dialysis; Risk Factors; Smoking; Vitamin B 12

A high level of total plasma homocysteine is a risk factor for atherosclerosis, which is an important cause of death in renal failure. We evaluated the role of this as a risk factor for vascular complications of end-stage renal disease.. Total fasting plasma homocysteine and other risk factors were documented in 176 dialysis patients (97 men, 79 women; mean age, 56.3 +/- 14.8 years). Folate, vitamin B12, and pyridoxal phosphate concentrations were also determined. The prevalence of high total homocysteine values was determined by comparison with a normal reference population, and the risk of associated vascular complications was estimated by multiple logistic regression. Total homocysteine concentration was higher in patients than in the normal population (26.6 +/- 1.5 versus 10.1 +/- 1.7 mumol/L; P < .01). Abnormally high concentrations (> 95th percentile for control subjects, 16.3 mumol/L) were seen in 149 patients (85%) with end-stage renal disease (P < .001). Patients with a homocysteine concentration in the upper two quintiles (> 27.8 mumol/L) had an independent odds ratio of 2.9 (CI, 1.4 to 5.8; P = .007) of vascular complications. B vitamin levels were lower in patients with vascular complications than in those without. Vitamin B6 deficiency was more frequent in patients than in the normal reference population (18% versus 2%; P < .01).. A high total plasma homocysteine concentration is an independent risk factor for atherosclerotic complications of end-stage renal disease. Such patients may benefit from higher doses of B vitamins than those currently recommended.

Topics: Aged; Aging; Arteriosclerosis; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Odds Ratio; Osmolar Concentration; Peritoneal Dialysis, Continuous Ambulatory; Pyridoxine; Renal Dialysis; Risk Factors; Sex Distribution; Vitamin B 12

Iron deficiency involvement in the results of long-term replacement therapy of renal anemia with recormon, a preparation of recombinant human erythropoietin, has been studied in chronic renal failure patients on programmed hemodialysis. The effect of recormon subcutaneous administration to 51 patients was found reduced in 9 patients; in 5 of them the decreased sensitivity to recormon was attributed to iron deficiency. During a year of treatment the percentage of iron-deficient patients rose from 9.1% to 45% as a result of intensive uptake of iron in the course of erythropoiesis. Iron preparation as a corrective treatment contributed to hematocrit increment reducing effective doses of erythropoietin. In addition to routine control of ferritin and iron it is recommended to trace the degree of transferrin saturation in the course of recombinant erythropoietin therapy.

Topics: Anemia, Hypochromic; Drug Evaluation; Erythropoietin; Ferritins; Folic Acid; Folic Acid Deficiency; Humans; Iron; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Transferrin; Vitamin B 12; Vitamin B 12 Deficiency

We describe the first reported case of resistance to human recombinant erythropoietin (rhEPO) treatment caused by vitamin B12 deficiency in a chronic hemodialysis patient. Despite a normal B12 level before rhEPO treatment, resistant anemia together with a low B12 level and a megaloblastic bone marrow developed after only 8 months of rhEPO. There was a rapid reticulocyte response to B12 supplements, and transfusion requirements dropped from 2 units monthly to nothing. Atrophic gastritis was diagnosed through endoscopy and biopsy. Because of the fall in B12 level after 8 months of rhEPO treatment, we analyzed the results of routinely measured B12 levels in 30 hemodialysis patients treated with rhEPO, and found the mean B12 levels to be unchanged before and after rhEPO treatment. Although we found screening for B12 deficiency of little benefit, any patient with rhEPO resistance should have B12 levels tested, given the potentially serious extra-hematological effects of B12 deficiency.

Topics: Aged; Anemia; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Erythropoietin was applied subcutaneously to 49 patients, 41 have been treated by hemodialysis, 3 by continuous ambulatory peritoneal-dialysis, 5 had chronic progressive renal failure. Mean initial dose of erythropoietin was 139.4 U/kg/week and maintenance dose 115.9 U/kg/week. In 43% of patients serum ferritin was decreasing during treatment, and in 20% it was low before the commencing of the treatment. During erythropoietin therapy vitamin B12 was decreasing in 22% of the patients, and the substitution was necessary in 18%. Only in 1 patient it was necessary to substitute also folic acid. There were no nonresponders among erythropoietin treated patients. Elevation of blood pressure was observed in half of the patients, hypertensive encephalopathy in 1, and thrombosis of arterio-venous fistula in 3.

Topics: Adult; Anemia; Child; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Vitamin B 12

Vitamin B12 in plasma, folic acid in plasma and erythrocytes were examined in 11 patients in the polyuric stage of chronic renal failure without dialyzation treatment, in 38 patients included in a long-term dialyzation programme before and after 3 months' oral administration of folic acid--(2 X 5 mg week)--and in 23 patients after transplantation of the kidneys. In none of the examined groups vitamin B12) and folic acid deficiency in plasma was detected. A reduced folic acid level in erythrocytes, but still in the reference range, was found in patients in the long-term dialyzation programme without supplementation. Supplementation with folic acid increased its concentration in plasma 4.5 times and in red cells 5.5 times. Haemodialysis did not influence the concentration of the examined indicators in plasma and red cells. According to the recorded results it is not necessary to supplement patients in long-term dialyzation programme and after renal transplantation with vitamin B12 and folic acid, if their dietary protein intake is not restricted.

Topics: Female; Folic Acid; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Renal Dialysis; Vitamin B 12

Much attention is being devoted to the efficient removal of beta 2-microglobulin from patients on hemodialysis as it may cause amyloidosis. The objective of the present article is to clarify the beta 2-microglobulin removal characteristics of dialysis membranes having varying water contents and pore radii. For membranes of regenerated cellulose, polymethylmethacrylate (PMMA) and ethylenevinyl alcohol (EVA), solute and pure water permeability and water content were determined by the standard methods. Data analysis using a tortuous pore model allows determination of pore radius, surface porosity, and tortuosity, and hence, the sieving coefficient as a function of Stokes radius. Based on the tortuous pore model calculation, little beta 2-microglobulin is removed from patients on hemodialysis by regenerated cellulose and PMMA membranes, but EVA membranes, with a sieving coefficient of 0.5, are capable of removing it. The solute permeability for urea is about 2 orders greater than that for beta 2-microglobulin.

Topics: beta 2-Microglobulin; Blood Proteins; Blood Urea Nitrogen; Diffusion; Humans; Kidney Failure, Chronic; Kidneys, Artificial; Membranes, Artificial; Molecular Weight; Renal Dialysis; Serum Albumin; Vitamin B 12

Topics: Adult; Aged; Autonomic Nervous System Diseases; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Uremia; Vitamin B 12

Topics: Humans; Kidney Failure, Chronic; Renal Dialysis; Vitamin B 12

Vitamin supplementation for dialysis patients is still controversial. In our study, we followed longitudinally over a period of a year, 15 patients on chronic hemodialysis who were deprived of vitamin supplementation. Microbiological assays were used to determine the levels of five vitamins of the B group (folate, niacin, B12, B6, and thiamine). Vitamin C was measured chemically. During the observation period when vitamins were not supplemented, a marked drop of many of these vitamins in blood levels were encountered. For vitamins B12 and C, the plasma levels remained within the normal range in all the subjects studied. For the other vitamins, the blood levels were found to be low in a few patients. Our data suggest that vitamin supplementation is probably not needed in most stable hemodialysis patients as it is recommended now, and that perhaps, if supplementation is indicated, less should be given than is presently prescribed. Further research is needed in this area.

Topics: Adult; Aged; Ascorbic Acid; Female; Folic Acid; Follow-Up Studies; Humans; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Niacin; Pyridoxine; Renal Dialysis; Thiamine; Vitamin B 12; Vitamins

Plasma B12, folate, B6 and thiamine, and red blood cell folate, thiamine and niacin levels were monitored for a period of 6 months in 15 clinically stable, chronic hemodialysis patients who were not supplemented with the water-soluble vitamins. Microbiological assays were used to determine the blood levels of the water-soluble vitamins. Over the period of 6 months, none of the patients had plasma or red cell vitamin levels below the normal range. No appreciable changes were observed in the plasma and red blood cell vitamin levels before and after dialysis in 5 patients. This study showed that chronic hemodialysis patients are able to maintain normal plasma and red cell levels of some water-soluble vitamins without daily supplementation.

Topics: Adult; Aged; Erythrocytes; Female; Folic Acid; Humans; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Niacin; Plasma; Pyridoxine; Renal Dialysis; Thiamine; Vitamin B 12; Vitamin B Complex

Blood concentration of water-soluble vitamins were measured in patients with mild chronic renal insufficiency, uremic undialyzed and dialyzed patients and control subjects. The whole blood concentration of B1 was significantly lower in dialyzed patients. Plasma levels of B2 were elevated in uremic and dialyzed patients and plasma B6 was significantly increased in dialyzed patients. Serum levels of B12 and folic acid were elevated in uremic and dialyzed patients. The results of this study differ from those reported from Europe and the U.S.A. These geographical differences may arise primarily from differences in staple food, vegetable intake, and traditional methods of food preparation.

Topics: Adult; Aged; Ascorbic Acid; Female; Folic Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pyridoxine; Renal Dialysis; Riboflavin; Thiamine; Uremia; Vitamin B 12; Vitamins

Deficiencies of water-soluble vitamins may occur in uremic patients mainly because of restricted consumption and of loss during chronic hemo- and peritoneal dialysis. Although the daily requirement for most vitamins is not well defined in chronic renal failure supplementation of the vitamins thiamine, riboflavin, pyridoxine, pantothenic acid, niacin and ascorbic acid, the form of one multivitamin preparation without vitamin A as well as folic acid in dialysis patients after each dialysis is recommended. There is no need for vitamin B12, vitamin A and vitamin E.

Topics: Ascorbic Acid; Avitaminosis; Biotin; Folic Acid; Humans; Kidney Failure, Chronic; Niacin; Pantothenic Acid; Pyridoxine; Riboflavin; Thiamine; Vitamin A; Vitamin B 12; Vitamin E; Vitamin K; Vitamins

It is difficult to assess the vitamin B12 metabolism in chronic renal insufficiency. In varying numbers out of a total of 88 nephropathy patients with varying degrees of insufficiency (22 patients without restriction of kidney function, 53 patients with chronic renal insufficiency in the stage of compensated retention and 13 haemodialysis patients) the Schilling test was performed and the serum vitamin B12 level was measured in fasting and 4, 6, 8 and 10 hours after oral administration of 2000 micrograms of vitamin B12. Regardless of the volume of urine, the Schilling test must be treated critically with serum creatinine values between 150 and 300 mumol/l and beyond 300 mumol/l it is no longer of diagnostic value. Serum vitamin B12 measurement after oral administration of 2000 micrograms of vitamin B12 allows vitamin resorption in the ileum to be qualitatively demonstrated on the basis of the curve. In most renal insufficiency patients the serum vitamin B12 level was increased, but this does not exclude the possibility of vitamin B12 deficiency.

Topics: Adolescent; Adult; Aged; Cobalt Radioisotopes; Creatinine; Female; Glomerulonephritis; Humans; Intestinal Absorption; Kidney Failure, Chronic; Male; Middle Aged; Pyelonephritis; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Over the first three months of continuous ambulatory peritoneal dialysis (CAPD) the level of hemoglobin (Hb) rises significantly in most patients. To elucidate this further we studied the hematological response over 3 months of 8, previously non-transfused new patients treated with CAPD. Mean Hb rose by +2.78 g/dl (P less than 0.02). Mean RCM rose by 284 ml (37.7%) (P less than 0.05) and 3.7 ml/kg (29.6%) (P less than 0.05). PV fell relative to BW only, by -8.6 ml/kg (P less than 0.05). There was no significant change in serum vitamin B12 or folate concentrations or evidence of hemolysis. Plasma ferritin fell in all patients, but hematological changes of iron deficiency appeared in only one. Bio-assayable erythropoietin (EPO) levels were generally in the normal range, but inappropriately low for the degree of anemia. EPO did not change significantly apart from in two patients, one with polycystic disease. These results indicate that over the initial 3 months of therapy the majority of CAPD patients have a rise in Hb, due mainly to a rise in RCM, unrelated to changes in serum EPO level.

Topics: Adult; Body Weight; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Folic Acid; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Plasma Volume; Vitamin B 12

The paper is concerned with materials characterizing physicochemical properties of haemosorbents of varying grades. Adsorption of different uraemic toxins was studied. The possibility of microembolization of internal organs and tissues with haemosorbent particles was explored in the course of prolonged treatment with the use of haemosorption. Different approaches to connecting the sorption column to the dialyzer were examined to disclose an optimal variant. The authors report the results of applying haemosorption in patients who had received haemodialysis therapy to prevent complications. The blood response to the prolonged haemosorption treatment was analyzed. It is recommended that long-term (6-7 hours) sessions of haemosorption might be performed using carbons having high sorption capacity.

Topics: Adolescent; Adsorption; Adult; Charcoal; Creatinine; Female; Hemoperfusion; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Uric Acid; Vitamin B 12

Topics: Adult; Aged; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Urea; Vitamin B 12

Serum B12 and erythrocyte folate were measured in 16 non-dialysed uraemic patients, 28 peritoneal dialysed patients, 28 haemodialysed patients, 14 renal transplanted patients with normal renal function and 49 healthy control subjects. Serum B12 values in non-dialysed uraemic patients were higher than in control subjects (P less than 0.01). Serum B12 values in peritoneal dialysed, haemodialysed and transplanted patients were not significantly different from the control group. Erythrocyte folate values in non-dialysed uraemic patients were lower than in controls (P less than 0.03), but all subjects had values within the normal range. Erythrocyte folate values in peritoneal dialysed, haemodialysed and renal transplanted patients were not significantly different from the control group, although 2 peritoneal and 6 haemodialysed patients had subnormal values. Blood and bone marrow examination, performed in 64 patients, demonstrated no megaloblastic changes.

Topics: Adolescent; Adult; Child; Chronic Disease; Erythrocytes; Female; Folic Acid; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Renal Dialysis; Transplantation, Homologous; Uremia; Vitamin B 12

Topics: Humans; Intestinal Absorption; Kidney Failure, Chronic; Renal Dialysis; Vitamin B 12

Topics: Adolescent; Adult; Aged; Anemia; Female; Folic Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Vitamin B 12

Four patients on regular hemodialysis therapy with a persistent anemia and reduced serum vitamin B12 levels are discribed. In each case a significant improvement occurred with B12 therapy and it is suggested that the vitamin B12 content of a 70 g protein/day diet may not be adequate to maintain stores of the vitamin.

Topics: Adult; Anemia, Hypochromic; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Vitamin B 12

Thirty-one patients suffering from very advanced degrees of chronic renal insufficiency were studied. Ten received a hypoproteic diet as the only treatment and the remaining 21 were on a program of hemodialysis with a free diet and no vitamin supplements. Basal and pre- and post-dialysis plasma determinations of B12 vitamin and folic acid were carried out on them. Looking at the results it was verified that there was a significant reduction in the plasma values of both B12 vitamin and folic acid in the cases of low protein intake. In dialysis we saw that although folic acid was lost during sessions the free dietetic intake was enough to compensate for these losses. As for B12 vitamin, although it is described as dialyzable, we did not observe that its post-dialysis values disminished. Our conclusions indicate that a supplementary vitamin contribution is not necessary for patients who are on a program of hemodialysis.

Topics: Adult; Female; Folic Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Vitamin B 12

Blood concentrations of water soluble vitamins were studied in 29 undialyzed and 35 dialyzed patients with CRF, and 36 healthy volunteers. Effects of B6 administration on immunological parameters were studied in dialyzed patients. In dialyzed patients, whole blood B1 decreased, while plasma B2, B6 and serum B12 and folic acid increased. In undialyzed patients with uremia, plasma B2, serum B12 and folic acid increased, while plasma C decreased in patients with moderate CRF. Oral administration of B6 for 4 wks was associated with improved tuberculin skin tests and PHA mitogen responses in dialyzed patients. Supplementation of B1 is required for patients with CRF while B6 and C may be considered.

Topics: Ascorbic Acid; Folic Acid; Humans; Kidney Failure, Chronic; Lymphocytes; Pyridoxine; Renal Dialysis; Riboflavin; Thiamine; Tuberculin Test; Vitamin B 12; Vitamins

This study was designed to (1) develop a simple technique of estimating 'middle-molecule' clearances in peritoneal dialysis patients using vitamin B12 as a marker; (2) evaluate changes in small- and middle-molecule clearances during a single 24- or 36-hour peritoneal dialysis, and (3) determine if using 4.25% rather than 1.5% dextrose exchanges alters the clearances of small and middle molecules. Measurement of clearance following the intramuscular injection of vitamin B12 was found to be a reliable method of estimating the clearance of middle molecules. Small- and middle-molecule clearances remain constant throughout an individual 24- or 36-hour dialysis. In addition, small-molecule clearances increase significantly with 4.25% dextrose dialysate but return to prior values when 1.5% dextrose dialysate is reinstituted.

Topics: Humans; Injections, Intramuscular; Kidney; Kidney Failure, Chronic; Metabolic Clearance Rate; Peritoneal Dialysis; Toxins, Biological; Uremia; Vitamin B 12

A convertible and versatile dialysis system consisting of a PMMA hollow fiber unit and UFR controller is shown to be useful for evaluating the effect of solute and fluid removal rates on adequacy of dialysis. Post-dilution mode where high UFR is applied to the patient with matching or comparable dilution rate is concluded to be most effective modification for enhancing the clearance for "middle molecules", without sacrificing the removal rates for the small solutes.

Topics: Creatinine; Humans; Kidney Failure, Chronic; Kidneys, Artificial; Methylmethacrylates; Renal Dialysis; Ultrafiltration; Urea; Uric Acid; Vitamin B 12

Topics: Blood Urea Nitrogen; Creatinine; Glomerular Filtration Rate; Hematocrit; Humans; Kidney Failure, Chronic; Molecular Weight; Neural Conduction; Renal Dialysis; Vitamin B 12

Serum vitamin B12 concentrations were measured in 60 patients undergoing repetitive hemodialysis and in undialyzed patients with chronic renal failure. Dialysis patients had significantly lower serum vitamin B12 levels than the nondialyzed group 321 +/- SEM 38 pg/ml versus 793 +/- 100), and 19 of 60 dialysis patients had vitamin B12 Concentrations less than 200 pg/ml. Folic acid concentration was 5 times greater in dialysis than in nondialysis patients, presumably because the latter received daily supplementation with folic acid. Serum vitamin B12 concentrations fell progressively during the patient's course of dialysis. Neither inadequate dietary intake nor vitamin B12 malabsorption accounted for the differences in the serum vitamin B12 concentrations seen in the two groups. Serum vitamin B12 levels and nerve conduction velocities in 51 dialyzed patients showed a significant correlation. Six dialyzed patients with low serum vitamin B12 levels and slow nerve conduction velocities showed improvement in nerve conduction (+ 14.6 +/- 3.3 m/sec) following the parenteral use of pharmacological doses of vitamin B12. The cause of the low serum vitamin B12 concentration is not clear, nevertheless, alterations in serum vitamin B12 seen in some dialysis patients may be a factor in the persistence of abnormal nerve conduction and may be reversed with large doses of parenteral vitamin B12.

Topics: Absorption; Digestive System Physiological Phenomena; Folic Acid; Humans; Injections, Intravenous; Kidney Failure, Chronic; Neural Conduction; Peripheral Nervous System Diseases; Renal Dialysis; Time Factors; Vitamin B 12

Topics: Adult; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Vitamin B 12

Topics: Adult; Aged; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Vitamin B 12

Topics: Attention; Brain; Cognition; Decision Making; Electroencephalography; Humans; Kidney Failure, Chronic; Male; Memory, Short-Term; Nervous System; Renal Dialysis; Urea; Uremia; Vitamin B 12

Gastrointestinal iron absorption, by means of whole body counting, has been measured in 15 patients with chronic renal failure, not requiring dialysis. Whole body retention 14 days after oral administration of 10 muCi 59Fe together with a carrier dose of 10 mg Fe2+ was taken as expression of absorption. The percentage incorporation in the total erythrocyte mass of administered 59Fe (erythrocyte incorporation) and absorbed 59Fe (red cell utilization) was estimated as well. Iron absorption was 9.6+/-2.0 (S.D.)% (geometric mean) and erythrocyte incorporation 7.5+/-2.3 (S.D.)% (geometric mean) while red cell utilization averaged 80.3+/-4.8 (S.E.M.)% (arithmetic mean). None of these parameters were significantly different from those obtained in a normal control group (p greater than 0.5, p greater than 0.9 and p greater than 0.2, respectively). The correlation between iron absorption and erythrocyte incorporation was highly significant (r=1.00, p less than 0.001). Iron supplementation is often indicated in the investigated category of patients due to increased blood loss and insufficient iron intake and should be given orally in consideration of the normal gastrointestinal absorption.

Topics: Erythrocytes; Female; Folic Acid; Glucosephosphate Dehydrogenase; Humans; Intestinal Absorption; Iron; Kidney Failure, Chronic; Male; Transferrin; Vitamin B 12

Topics: Adenylyl Cyclases; Adrenergic beta-Agonists; Adult; Anemia, Hemolytic; Anemia, Pernicious; Blood Cell Count; Cell Membrane; Cyclic AMP; Erythrocytes; Erythropoiesis; Female; Fluorides; Hemolysis; Humans; In Vitro Techniques; Isoproterenol; Kidney Failure, Chronic; Male; Middle Aged; Reticulocytes; Time Factors; Vitamin B 12

Topics: Adolescent; Adult; Blood Pressure; Blood Urea Nitrogen; Body Weight; Cobalt Radioisotopes; Creatinine; Evaluation Studies as Topic; Female; Hematocrit; Hemodialysis, Home; Humans; Iodine Radioisotopes; Iothalamic Acid; Kidney Failure, Chronic; Kidneys, Artificial; Male; Middle Aged; Models, Biological; Phosphates; Time Factors; Uric Acid; Vitamin B 12

Topics: Adult; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Kidneys, Artificial; Male; Membranes, Artificial; Middle Aged; Motor Neurons; Neural Conduction; Permeability; Polymers; Renal Dialysis; Time Factors; Ultrafiltration; Vitamin B 12

Topics: Adult; Anemia, Pernicious; Cobalt Radioisotopes; Gastrectomy; Humans; Kidney Failure, Chronic; Schilling Test; Vitamin B 12

Serum folate and vitamin B(12) levels have been measured in 32 patients with renal failure. The initial mean serum folate level was raised above normal in seven patients with acute renal failure whereas the mean level in eight patients severely ill from chronic renal failure was significantly lower than normal. Serum folate levels fell during peritoneal dialysis and rose between dialyses in all these patients and also in one patient who was dialysed for acute pancreatitis.The mean serum B(12) level was raised in patients with both acute and chronic renal failure, but there was no consistent change in serum B(12) level during dialysis.Hypersegmented polymorphs were present in the peripheral blood film of most of the patients with acute or chronic renal failure. Their presence bore no relation to the clinical state, blood urea, serum folate, or serum B(12) level of the patients.

Topics: Acute Kidney Injury; Adolescent; Adult; Female; Folic Acid; Humans; Kidney Failure, Chronic; Leukocytes; Male; Middle Aged; Pancreatitis; Peritoneal Dialysis; Urea; Vitamin B 12

Topics: Adolescent; Adult; Alpha-Globulins; Anemia; Blood Cell Count; Blood Sedimentation; Female; Humans; Infections; Kidney Failure, Chronic; Male; Neoplasms; Protein Binding; Vitamin B 12

Topics: Adult; Aged; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Pernicious; Bone Marrow Examination; Cestode Infections; Erythrocytes; Female; Hematocrit; Hemoglobinometry; Humans; Hyperthyroidism; Hypothyroidism; Iron; Kidney Failure, Chronic; Leukocyte Count; Male; Middle Aged; Neoplasms; Pregnancy; Transferases; Vitamin B 12

Topics: Anemia, Macrocytic; Blood Urea Nitrogen; Bone Marrow Examination; Folic Acid; Folic Acid Deficiency; Hematopoiesis; Humans; Kidney Failure, Chronic; Renal Dialysis; Uremia; Vitamin B 12