vitamin-b-12 and Renal-Insufficiency--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

We reviewed reasons for the high cardiovascular risk (CVD) of patients with chronic kidney disease (CKD), and explored alternatives to treatment of traditional risk factors to reduce CVD in CKD.. Besides traditional risk factors, patients with CKD are exposed to uremic toxins of two kinds: systemically derived toxins include asymmetric dimethylarginine (ADMA), total homocysteine (tHcy), thiocyanate, tumor necrosis factor alpha, and interleukin 6. Gut-derived uremic toxins (GDUT), products of the intestinal microbiome, include hippuric acid, indoxyl sulfate, p-cresyl sulfate, p-cresyl glucuronide, phenylacetylglutamine, and trimethylamine N-oxide (TMAO). Cyanocobalamin is toxic in patients with CKD. Approaches to reducing plasma levels of these uremic toxins would include diet to reduce GDUT, kidney transplantation, more intensive dialysis, and vitamin therapy to lower tHcy with methylcobalamin rather than cyanocobalamin. The high CVD risk in CKD requires consideration of therapies beyond treatment of traditional risk factors.

Topics: Cardiovascular Diseases; Cerebrovascular Disorders; Humans; Renal Insufficiency, Chronic; Toxins, Biological; 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

to determine whether the administration of folic acid, vitamin B6 and vitamin B12 would lead to reduction of cardiovascular complication and mortality among CKD patients.. a search was conducted on PubMed and Google. The selection of title and abstract was conducted using inclusion and exclusion criterias, which led to six relevant articles. The selected studies were critically appraised for its validity, importance and applicability.. the administration of folic acid and vitamin B reduce homocysteine level among CKD patients. Despite homocysteine level reduction, all six studies reported similar findings that folic acid and vitamin B supplementation did not significantly reduce cardiovascular complication and mortality.. treatment with folic acid, vitamin B6 and vitamin B12 did not reduce cardiovascular complication and mortality among CKD patients.

Topics: Cardiovascular Diseases; Evidence-Based Medicine; Folic Acid; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamin B Complex

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

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

Sites and mechanisms regulating the supply of homocysteine (Hcy) to the circulation are unexplored in humans. We studied the exchange of Hcy across the forearm in CKD patients (n = 17, eGFR 20 ± 2 ml/min), in hemodialysis (HD)-treated patients (n = 14) and controls (n = 9). Arterial Hcy was ~ 2.5 folds increased in CKD and HD patients (p < 0.05-0.03 vs. controls). Both in controls and in patients Hcy levels in the deep forearm vein were consistently greater (+~7%, p < 0.05-0.01) than the corresponding arterial levels, indicating the occurrence of Hcy release from muscle. The release of Hcy from the forearm was similar among groups. In all groups arterial Hcy varied with its release from muscle (p < 0.03-0.02), suggesting that muscle plays an important role on plasma Hcy levels. Forearm Hcy release was inversely related to folate plasma level in all study groups but neither to vitamin B12 and IL-6 levels nor to muscle protein net balance. These data indicate that the release of Hcy from peripheral tissue metabolism plays a major role in influencing its Hcy plasma levels in humans and patients with CKD, and that folate is a major determinant of Hcy release.

Topics: Folic Acid; Homocysteine; Humans; Muscle, Skeletal; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin B 12

Chronic Kidney Disease (CKD) is an emerging public health issue with a fast-growing global prevalence. Impairment in vitamin B12 metabolism is considered a nontraditional risk factor of poor outcomes associated with CKD, and there is greater interest from the scientific community than ever before to explore the role and influence of vitamin B12 in CKD. Homocysteine metabolism forms an important component of the vitamin B12 metabolic pathway. Hyperhomocysteinemia is frequently observed in CKD and End-Stage Kidney Disease (ESKD), but its representation as a prognostic marker for CKD outcomes is still not fully clear. This chapter reviews the vitamin B12 and homocysteine metabolic pathways and their dysfunction in CKD states. Biochemical factors and the MTHFR genetic polymorphisms which disrupt vitamin B12 and homocysteine metabolism are explored. The mechanisms of homocysteine-mediated and vitamin B12-mediated tissue damage in CKD are discussed. This chapter reviews current perspective on definition and measurement of plasma vitamin B12 levels in the CKD population. Updated evidence investigating the prognostic role of vitamin B12 for CKD outcomes is presented. Findings from major clinical trials conducted relating to outcomes from multivitamin (including folic acid and vitamin B12) supplementation in nondialysis and dialysis-dependent CKD are highlighted. The prognostic value of vitamin B12 and effects of vitamin B12 supplementation in the context of kidney transplantation and acute kidney injury is also reviewed. Future research considerations are summarized based on evidence gaps in our knowledge base of this topic. Greater abundance of high-level evidence to guide an approach toward vitamin B12 measurement, monitoring and supplementation in CKD may contribute to improved clinical outcomes.

Topics: Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Renal Insufficiency, Chronic; Vitamin B 12

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for >3 months, with implications for health. Therapeutic interventions at earlier stages can prevent or ameliorate most of the complications of decreased kidney function, as well as slow the progression to kidney failure. Coronary artery disease (CAD) is the most common cause of death in CKD patients. Low serum folic acid, low serum vitamin B12 and high serum homocysteine are commonly associated with CKD.. This work was a single-centre, cross-sectional, descriptive study which included 100 patients who met the criteria for CKD, as per KDIGO guidelines. Serum vitamin B12, serum folic acid, serum homocysteine and eGFR for each patient was measured and their association with the renal function and mortality outcome was noted.. A total of 100 patients (M:F=68:32) of chronic kidney disease were analyzed. Mean age of the study population was 51.55±16.23 years. On applying Pearson correlation between S. folic acid and eGFR, a linear correlation was found (p=0.001, correlation= 0.331). Similarly, an inverse correlation between S. homocysteine and eGFR (p<0.001, correlation=-0.573) was established. 15% patients died during the course of study. The mean folic acid among patients who died and patients who survived was 3.99±4.04ng/ml and 10.72±7.58ng/ml, respectively. The difference was statistically significant. The mean eGFR among those who died (mean=4.04±3.22ml/mint/1.73m2) was significantly lower (p<0.001) than the patients who survived during the study (mean=.16.22±12.66 ml/ mint/1.73m2).. Higher levels of homocysteine were more common in CKD patients as the disease progressed. It was also associated with poorer outcome (i.e. mortality risk). Advanced CKD staging was associated with increased mortality and lower folate levels. However, no association between serum vitamin B12 and renal/mortality outcome could be established in this study.

Topics: Adult; Aged; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Vitamin B 12

Topics: Disease Progression; Folic Acid; Humans; Renal Insufficiency, Chronic; Vitamin B 12; Vitamins

Iron deficiency is frequent in haemodialysis (HD) patients with chronic kidney disease (CKD), and intravenous iron is an established therapy for these patients. This study assessed treatment routine, effectiveness, and safety of iron isomaltoside (IIM) 5% (Diafer®) in a HD cohort.. This prospective observational study included 198 HD patients converted from iron sucrose (IS) and treated with IIM according to product label and clinical routine. Data for IIM were compared to historic data for IS in 3-month intervals. The primary endpoint was to show non-inferiority for IIM versus IS in haemoglobin (Hb) maintenance.. Most patients (> 60%) followed a fixed low-dose iron treatment protocol. Three minutes were required for preparation and administration of IIM. Erythropoiesis-stimulating agent (ESA) was used in > 80% of patients during both IIM and IS phases. The maintenance of Hb was similar with both iron drugs; the mean Hb level was 11 g/dL, and the mean change of 0.3 g/dL (95% confidence interval: 0.1, 0.5) for IIM 0-3 months compared to IS demonstrated non-inferiority. Nine adverse drug reactions were reported in 2% of patients administered IIM. All patients had uneventful recoveries. The frequency of metallic taste was higher with IS compared to IIM (34% versus 0.5%, p < 0.0001).. IIM is effective and well tolerated by CKD patients on HD. IIM was non-inferior to IS in maintenance of Hb, and had similar ESA requirements. The fast-push injection of IIM may enable logistical benefits in clinical practice, and the low frequency of metallic taste contributes to patient convenience.. ClinicalTrials.gov identifier NCT02301026, study registered November 25, 2014.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Blood Transfusion; Combined Modality Therapy; Disaccharides; Drug Therapy, Combination; Dysgeusia; Female; Ferric Compounds; Folic Acid; Hemoglobins; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin B 12

Introduction: According to present knowledge, hyperhomocysteinemia is one of the risk factors of cardio-vascular pathology. Patients with chronic kidney disease are known to develop hyperhomocysteinemia more often than those in general population. Іmportant cause of hyperhomocysteinemia is the deficiency of vitamins В6, В9 and В12 that are involved in homocysteine metabolism. Vitamins deficiency, we believe, can be one of the causes of hyperhomocysteinemia in the patients with chronic renal failure. The aim: To analyze the plasma homocysteine level in patients with chronic kidney disease and its assosiation with the levels of vitamins B6, B9, B12 in Ukraine.. Materials and methods: The study involved 148 persons with different stagesis of chronic kidney disease who underwent immunoenzyme determination of total plasma homocysteine, B9, cobalamin and vitamin В6 status.. Results: It was found that in ukrainian patient population with chronic kidney disease 58.7% of patients have hyperhomocysteinemia. Homocysteine level was shown to increase with the increase of chronic kidney disease stage. Supply of vitamins В6, В9 та В12 in the patients with chronic kidney disease was lower than in apparently healthy persons, but there was significant decrease of folic acid level proportionally to the increase of chronic kidney disease stage. There was close relationship between homocysteine level and folic acid status in the patients with chronic kidney disease, but it appeared to be independent on cobalamin and pyridoxin status.. Conclusions: The obtained data are promising for finding effective means of correction of hyperhomocysteinemia in patients with chronic kidney disease by normalizing the vitamin status of such patients.

Topics: Folic Acid; Homocysteine; Humans; Renal Insufficiency, Chronic; Ukraine; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Topics: Folic Acid; Humans; Hydrogen Sulfide; Hyperhomocysteinemia; Renal Insufficiency, Chronic; Vitamin B 12

Hyperhomocysteinemia (hHcy) is a risk factor in the progression of chronic kidney disease (CKD). In type 2 diabetes (T2D), hHcy is strongly associated with increased risk of cardiovascular disease. Vitamin B12 and folic acid supplementation have been reported to lower homocysteine (tHcy) levels, but no data on plasma tHcy, cysteine (Cys), folate and vitamin B12 levels in T2D-CKD patients are reported.. tHcy and Cys levels were analyzed in 178 T2D-CKD patients by high performance liquid chromatography (HPLC) with fluorescence detection. In addition, we determined folate and vitamin B12 levels using a chemiluminescence method.. tHcy and Cys levels were increased in T2D patients, and this rise positively correlated with the CKD stage (P < 0.001). Folate levels were comparable to controls at various CKD stages, whereas vitamin B12 levels were lower, except at stage IV. We did not find any correlation between B-vitamins and levels of tHcy and Cys, regardless of the CKD stage.. This is the first study reporting tHcy, Cys and B-vitamins status in T2D-CKD patients. Although limited to our cohort of 178 patients, our findings could be helpful in clarifying the conflicting literature regarding B-vitamins supplementation. Further studies are necessary before any Hcy-lowering therapy can be safely established in T2D-CKD subjects.

Topics: Aged; Aged, 80 and over; Biomarkers; Chromatography, High Pressure Liquid; Cysteine; Diabetes Mellitus, Type 2; Disease Progression; Female; Folic Acid; Homocysteine; Humans; Male; Renal Insufficiency, Chronic; Vitamin B 12

Topics: Asian People; Biomarkers; Blood Glucose; C-Reactive Protein; Female; Folic Acid; Fructosamine; Glycated Hemoglobin; Hemoglobins; Humans; Linear Models; Male; Multivariate Analysis; Renal Insufficiency, Chronic; Serum Albumin; Sex Factors; Vitamin B 12; White People

Hyper-homocysteinemia (HHcy) is associated with microalbuminuria and glomerular injury in general and diabetic populations. However, HHcy's role in hypertensive patients was not studied. We investigated whether HHcy is an independent risk factor for renal function decline and development of chronic kidney disease (CKD) in hypertensive men and women. This was a community-based prospective cohort study of 2,387 hypertensive adults without CKD at baseline, with a mean follow-up of 4.4 years. Baseline and follow-up levels of plasma Hcy, folate, vitamin B12, blood pressure and other pertinent covariables were obtained. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/per 1.73 m(2) and an eGFR decline rate >1 ml/min/per 1.73 m(2)/year. There was a graded association between Hcy tertiles and eGFR decline. Subjects in the 3(rd) tertile of Hcy levels had an accelerated rate of eGFR decline and an increased risk of incident CKD, as compared with those in the 1st tertile, after adjusting for age, gender, baseline diabetes, SBP, BMI, smoking, dyslipidemia, eGFR, folate and vitamin B12 levels. In conclusion, in this prospective cohort of Chinese hypertensive adults, elevated baseline plasma Hcy can serve as an independent biomarker to predict renal function decline and incident CKD.

Topics: Aged; Blood Pressure; Cohort Studies; Demography; Female; Folic Acid; Follow-Up Studies; Glomerular Filtration Rate; Homocysteine; Humans; Hyperhomocysteinemia; Hypertension; Kidney; Male; Middle Aged; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Vitamin B 12

The cblE disorder is an inherited disorder of vitamin B12 metabolism that results in elevated levels of homocysteine and decreased methionine in body fluids. Renal complications have been reported in patients with cblC disease, but not in those with cblE disease. The renal complications of cblC disease include thrombotic microangiopathy (TMA), neonatal hemolytic uremic syndrome, chronic renal failure, tubulointerstitial nephritis and proximal renal tubular acidosis. Previously, we reported a patient with cblC disease who had an atypical glomerulopathy that manifested with proteinuria and progressive renal insufficiency.. Studies were done on cultured fibroblasts. Renal biopsy tissue was examined by light and electron microscopy. There was decreased incorporation of labeled methyltetrahydrofolate and decreased synthesis of methylcobalamin. Complementation analysis placed the patient into the cblE complementation group. The findings from the histological and ultrastructural studies of renal biopsy were similar, but not identical, to those of idiopathic membranoproliferative glomerulonephritis (MPGN) and overlapped with those of TMA.. We describe a patient with cblE disease who had an atypical glomerulopathy similar to MPGN. Additional findings included migraine headaches, hypothyroidism and livedo reticularis.

Topics: Anemia, Megaloblastic; Biopsy; Cells, Cultured; Disease Progression; Female; Fibroblasts; Genetic Complementation Test; Genetic Predisposition to Disease; Glomerulonephritis, Membranoproliferative; Homocystinuria; Humans; Hydroxocobalamin; Hypothyroidism; Kidney; Livedo Reticularis; Migraine Disorders; Phenotype; Predictive Value of Tests; Renal Insufficiency, Chronic; Time Factors; Vitamin B 12; Vitamin B Complex; Young Adult

Some studies comparing serum cobalamin in individuals with and without sickle cell disease (SCD) have suggested a higher prevalence of cobalamin deficiency in SCD but others have not. Our aim was to prospectively compare cobalamin status in African-Americans with and without SCD.. We analyzed blood samples from 86 subjects in two groups: SCD (n = 29) and non-SCD (n = 57). Serum cobalamin, folate, homocysteine, methylmalonic acid (MMA), anti-intrinsic factor antibody, Helicobacter pylori antibody, and gastrin were measured and compared.. The median cobalamin was 235 pM in the SCD group vs. 292 pM in the non-SCD group (P-value = 0.014). No significant differences in MMA or homocysteine were seen. Using the criteria of a low cobalamin and an elevated MMA or an elevated MMA alone, cobalamin deficiency was suggested in 4 (13.8%) in the SCD group and 6 (10.5%) in the non-SCD group. Two of these SCD patients and four of these control subjects had chronic renal disease, which may lead to elevated MMA in the absence of cobalamin deficiency. The remaining four met criteria for cobalamin deficiency, 2 (6.9%) in the SCD group and 2 (3.5%) in the non-SCD group (P = 0.6).. A lower cobalamin was observed in SCD patients without a higher prevalence of cobalamin deficiency. The inclusion of haptocorrin and holotranscobalamin measurement in future studies may provide a better assessment of cobalamin status in this patient group.

Topics: Adult; Anemia, Sickle Cell; Black or African American; Cross-Sectional Studies; District of Columbia; Homocysteine; Hospitals, Teaching; Humans; Male; Methylmalonic Acid; Middle Aged; Nutritional Status; Prevalence; Prospective Studies; Renal Insufficiency, Chronic; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult