vitamin-b-12 and Kidney-Diseases

A high serum vitamin B12 level (hypercobalaminemia) is a underestimated anomaly. Clinically, it can be paradoxically accompanied by signs of deficiency, which are related to defects in tissue uptake of vitamin B12. The increase in the level of serum cobalamin occurs mainly in serious diseases that require early diagnosis: hemoblastosis, liver and kidney diseases, etc. This review presents data on the metabolism of vitamin B12 and the potential significance of increasing its level as a marker for the early diagnosis of these diseases.. Гиперкобаламинемия - синдром повышения уровня витамина B12 в сыворотке крови, значение которого в клинической практике часто недооценивается. Это явление может сопровождаться парадоксальными с клинической точки зрения признаками гиповитаминоза витамина В12, отражающими наличие функционального дефицита, обусловленного дефектами потребления витамина тканями. Этиологическими факторами повышения уровня кобаламина в сыворотке крови являются преимущественно тяжелые заболевания, при которых особое значение для прогноза имеет ранняя диагностика: солидные опухоли, злокачественные гематологические новообразования, а также заболевания печени и почек с признаками их недостаточности. В настоящем обзоре представлены данные об обмене витамина В12 и потенциальной значимости повышения его уровня как маркера ранней диагностики этих заболеваний.

Topics: Biomarkers; Humans; Kidney Diseases; Liver; Liver Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Cobalamin C deficiency (cblC) is the most common inborn error of vitamin B

Topics: Humans; Kidney Diseases; Vitamin B 12; Vitamin B 12 Deficiency

It is well-established that more than 8% of patients examined for vitamin B12 deficiency unexpectedly have increased plasma levels of the vitamin, but so far there are no guidelines for the clinical interpretation of such findings. In this review, we summarise known associations between high plasma cobalamin and diseases. We report associations mainly with cancer, liver and kidney diseases, but also with a number of other diagnostic entities. The pathogenic background is poorly understood and is likely to be multi-factorial, involving increased concentrations of one or both of the circulating cobalamin binding proteins, transcobalamin and haptocorrin. Based on current knowledge, we suggest a strategy for the clinical interpretation of unexpected high plasma cobalamin. Since a number of the associated diseases are critical and life-threatening, the strategy promotes the concept of 'think the worst first'. It is important to realise that high cobalamin levels can be an unspecific marker for cancer. If this can be ruled out, diseases of the liver and kidney should be considered.

Topics: Autoimmune Diseases; Communicable Diseases; Hematologic Neoplasms; Humans; Kidney Diseases; Liver Diseases; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Cobalamin (Cbl, vitamin B12) consists of a corrinoid structure with cobalt in the centre of the molecule. Neither humans nor animals are able to synthesize this vitamin. Foods of animal source are the only natural source of cobalamin in human diet. There are only two enzymatic reactions in mammalian cells that require cobalamin as cofactor. Methylcobolamin is a cofactor for methionine synthase. The enzyme methylmalonyl-CoA-mutase requires adenosylcobalamin as a cofactor. Therefore, serum concentrations of homocysteine (tHcy) and methylmalonic acid (MMA) will increase in cobalamin deficiency. The cobalamin absorption from diet is a complex process that involves different proteins: haptocorrin, intrinsic factor and transcobalamin (TC). Cobalamin that is bound to TC is called holotranscobalamin (holoTC) which is the metabolically active vitamin B12 fraction. HoloTC consists 6 and 20% of total cobalamin whereas 80% of total serum cobalamin is bound to another binding protein, haptocorrin. Cobalamin deficiency is common worldwide. Cobalamin malabsorption is common in elderly subjects which might explain low vitamin status. Subjects who ingest low amount of cobalamin like vegetarians develop vitamin deficiency. No single parameter can be used to diagnose cobalamin deficiency. Total serum cobalamin is neither sensitive nor it is specific for cobalamin deficiency. This might explain why many deficient subjects would be overlooked by utilizing total cobalamin as status marker. Concentration of holotranscobalamin (holoTC) in serum is an earlier marker that becomes decreased before total serum cobalamin. Concentrations of MMA and tHcy increase in blood of cobalamin deficient subjects. Despite limitations of these markers in patients with renal dysfunction, concentrations of MMA and tHcy are useful functional markers of cobalamin status. The combined use of holoTC and MMA assays may better indicate cobalamin status than either of them. Because Cbl deficiency is a risk factor for neurodegenerative diseases an early diagnosis of a low B12 status is required which should be followed by an effective treatment in order to prevent irreversible damages.

Topics: Aged; Animals; Biomarkers; Diet, Vegetarian; Humans; Intestinal Absorption; Kidney Diseases; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Biomarkers; Chronic Disease; Erythropoietin; Evidence-Based Medicine; Folic Acid; Hematinics; Hemoglobins; Humans; Iron; Kidney Diseases; Recombinant Proteins; Treatment Outcome; Vitamin B 12

Homocysteine is a sulfur-containing amino acid that arises during methionine metabolism. Although its concentration in plasma is only about 10 micromolar, even moderate hyperhomocysteinemia is associated with increased incidence of cardiovascular disease and Alzheimer's disease. Elevations in plasma homocysteine are commonly found as a result of vitamin deficiencies, polymorphisms of enzymes of methionine metabolism, and renal disease. Pyridoxal, folic acid, riboflavin, and Vitamin B(12) are all required for methionine metabolism, and deficiency of each of these vitamins result in elevated plasma homocysteine. A polymorphism of methylenetetrahydrofolate reductase (C677T), which is quite common in most populations with a homozygosity rate of 10-15 %, is associated with moderate hyperhomocysteinemia, especially in the context of marginal folate intake. Plasma homocysteine is inversely related to plasma creatinine in patients with renal disease. This is due to an impairment in homocysteine removal in renal disease. The role of these factors, and of modifiable lifestyle factors, in affecting methionone metabolism and in determining plasma homocysteine levels is discussed.

Topics: Avitaminosis; Cardiovascular Diseases; Creatinine; Folic Acid; Homocysteine; Humans; Incidence; Kidney Diseases; Life Style; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Nutritional Physiological Phenomena; Polymorphism, Genetic; Pyridoxal; Riboflavin; Vitamin B 12

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

The possible molecular mechanisms potentially inducing occupational disease among operating room personnel were examined; and the really dangerous anaesthetic agents were identified. As concerns the molecular mechanisms of parenchymatous injury, we surveyed: those connected with free radicals and biological reactive intermediates produced during halothane and nitrous oxide biotransformation; those coming from inorganic fluoride produced during biotransformation of any halogenated anaesthetic agent, and from inorganic bromide released during halothane metabolism; and, finally, those linked to vitamin B12 inactivation from nitrous oxide. Halothane and nitrous oxide can be considered as really dangerous anaesthetic agents for operating room personnel, and enflurane as an agent with marginal toxic power. On the contrary, isoflurane is a safe, useful compound, totally devoided of viscerotoxic effects. From data examined it is possible to conclude that an isoflurane-oxygen-air anaesthesia is safe for operating room personnel more than a balanced anaesthesia with intravenous drugs and nitrous oxide as maintenance.

Topics: Air Pollutants, Occupational; Biodegradation, Environmental; Bromides; Chemical and Drug Induced Liver Injury; Fluorides; Free Radicals; Halothane; Humans; Kidney Diseases; Nervous System Diseases; Nitrous Oxide; Occupational Diseases; Vitamin B 12

Noninvasive radionuclide procedures in the evaluation of renal disease have been accepted increasingly as effective and valuable alternatives to older clinical methods. The development of suitable radiopharmaceuticals labeled with high photon intensity radionuclides and with 99mTc in particular has stimulated this modality during the last few years. Currently several nearly ideal agents are available for anatomical and functional studies of kidney imparting very low absorbed radiation doses. These include 99mTc-GHA and 99mTc-DMSA for renal morphology and differential function evaluation, 99mTc-DTPA for GFR and 123I orthoiodohippurate for ERPF measurements. A suitable agent as a replacement for the latter labeled with 99mTc is actively being sought. Computer-assisted processing of dynamic renal function studies enables the observer to obtain a wealth of information related to the renal extraction, uptake, parenchymal transit and pelvic transit parameters of the agent administered into the bloodstream. Each of these parameters either globally or differentially contributes to a detailed evaluation of renal disease states. Several of these procedures have been validated against classical techniques clinically but more detailed information is being sought with the recently introduced radiopharmaceuticals. With the detailed validation and increasing recognition of the clinical utility of several of the radionuclidic procedures at many centers, it is hoped that radionuclide assessment of renal disorders ultimately will be made available routinely at all medical facilities.

Topics: Carbon Radioisotopes; Chlormerodrin; Chromium Radioisotopes; Diatrizoate; Glomerular Filtration Rate; Humans; Inulin; Iodine Radioisotopes; Iodohippuric Acid; Iothalamic Acid; Kidney Diseases; Mercury Radioisotopes; Organotechnetium Compounds; Pentetic Acid; Radiation Dosage; Radioisotopes; Radionuclide Imaging; Renal Circulation; Succimer; Sugar Acids; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid; Technetium Tc 99m Pentetate; Vitamin B 12

Topics: Angiography; Chlormerodrin; Chromium Isotopes; Cobalt Isotopes; Color; Edetic Acid; Glomerular Filtration Rate; Humans; Iodine Radioisotopes; Kidney; Kidney Diseases; Kidney Neoplasms; Mercury Isotopes; Methods; Radioisotope Renography; Radionuclide Imaging; Technetium; Vitamin B 12

Chronic kidney disease (CKD) is associated with an increased incidence of cardiovascular disease (CVD). The Anti-oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study showed that a multistep treatment strategy improved carotid intima-media thickness, endothelial function, and microalbuminuria in patients with stages 2 to 4 CKD. Increased plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been linked to greater CVD risk in patients with CKD. The aim of this study is to assess effects of the multistep intervention on plasma ADMA concentrations in the ATIC Study.. Secondary analysis of a randomized double-blind placebo-controlled trial.. 93 patients with creatinine clearance of 15 to 70 mL/min/1.73 m(2) (according to the Cockcroft-Gault equation) from 7 outpatient clinics in Amsterdam, The Netherlands.. The treatment group received sequential treatment consisting of pravastatin, 40 mg/d. After 6 months, vitamin E, 300 mg/d, was added, and after another 6 months, homocysteine-lowering therapy (folic acid, 5 mg/d; pyridoxine, 100 mg/d; and vitamin B(12), 1 mg/d, all in 1 tablet) were added and continued for another year. The control group received matching placebos.. Plasma ADMA levels.. 36 participants (77%) in the treatment group and 38 (83%) in the placebo group completed the study. Mean ADMA and symmetric dimethylarginine concentrations in the total study population were 0.53 +/- 0.07 (SD) and 1.14 +/- 0.46 mumol/L, respectively. After 24 months, there was no overall effect of the treatment strategy on ADMA concentrations (beta = -0.006; P = 0.27). Analysis of separate treatment effects suggested that vitamin E significantly decreased ADMA levels by 4% in the treatment group compared with the placebo group (multiple adjusted P = 0.02).. The study was a secondary analysis, power calculation was based on the primary end point of carotid intima-media thickness, mean plasma ADMA levels were relatively low.. Overall, a multistep treatment strategy consisting of pravastatin, vitamin E, and B vitamins had no effect on plasma ADMA levels in a stage 2 to 4 CKD population. This suggests that the beneficial effects of the intervention were not mediated by changes in ADMA levels. Possible ADMA-lowering effects of vitamin E deserve further attention.

Topics: Adult; Aged; Anticholesteremic Agents; Arginine; Carotid Arteries; Chronic Disease; Creatinine; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Kidney Diseases; Lipoproteins, LDL; Male; Middle Aged; Pravastatin; Vitamin B 12; Vitamin B 6; Vitamin E

Previous studies have shown that homocysteine influences the structure of lipoprotein(a) [Lp(a)] and its affinity to fibrin, and that there is an increased risk of vascular disease when both homocysteine and Lp(a) are elevated. The aim of this study was to determine whether there is a correlation between increased total homocysteine (tHCY) and high Lp(a) concentrations, and whether increased concentrations of tHCY affect the concentration of unbound serum apolipoprotein(a) [Apo(a)]. Forty-seven male subjects recruited from a primary prevention screening program with normal serum creatinine and Lp(a) concentrations above 30 mg/dL were included and underwent a standardized oral methionine-loading test to increase the plasma tHCY concentration. This increase might lead to a modification of the Apo(a) structure, thus possibly influencing the serum concentration of unbound Apo(a). Fasting blood samples were taken before the tests and after 6 hours. The median values of tHCY increased about 4-fold after the methionine-loading test. Fasting tHCY did not show an association with Apo(a) and a post-methionine load increase of unbound Apo(a) was not observed. Backward multiple linear regression analysis, however, revealed that only post-load tHCY was independently and significantly influenced by Lp(a). Furthermore, Lp(a) correlated significantly with post-load tHCY, but not with fasting tHCY. Subdividing the subjects according to the Lp(a) concentration showed a significantly higher median concentration of tHCY after methionine load in subjects with Lp(a) over 50 mg/dL compared to subjects with Lp(a) under 50 mg/dL (P =.009). A similar cut-off was seen for post-load Apo(a) at 7.3 mg/dL (P =.04). Factors such as age, C677T-methylene-tetrahydrofolate-reductase (MTHFR) mutation, folate, vitamin B(12), and creatinine showed no significant influence on post-load tHCY in the different subgroups. The reasons for our findings remain partially unclear. However, considering our results and the current knowledge on the association of tHCY and Lp(a) concentration with the renal function, we hypothesize that both parameters may be linked by commencing renal metabolic dysfunction. It should be stressed that our hypothesis is speculative and that further studies will be necessary to improve the understanding of the interrelation of tHCY and Lp(a) concentration.

Topics: Apolipoproteins A; Creatinine; Folic Acid; Humans; Hyperhomocysteinemia; Kidney Diseases; Lipoprotein(a); Male; Methionine; Middle Aged; Vitamin B 12

Pathological similarities between atherosclerosis and glomerulosclerosis suggest that risk factors for the two processes may be similar. Elevated total homocysteine (tHcy) levels and low B vitamin levels are risk factors for atherosclerosis, but have not been evaluated sufficiently as risk factors for the progression of kidney disease.. Frozen samples from the Modification of Diet in Renal Disease Study were assayed for serum tHcy, cysteine, pyridoxal 5-phosphate (PLP), folate, and vitamin B12 levels in 804 participants. These factors were evaluated in both continuous and categorical analyses as risk factors for glomerular filtration rate (GFR) decline by using univariate and multivariable analyses.. At baseline, mean tHcy levels in study A (GFR, 25 to 55 mL/min/1.73 m2) and study B (GFR, 13 to 24 mL/min/1.73 m2) were 16.9 micromol/L (median, 15.6 micromol/L) and 23.0 micromol/L (median, 20.5 micromol/L), respectively. Mean follow-up was 2.2 years. Mean GFR declines were -4.35 and -3.65 mL/min/y in studies A and B, respectively. There was no significant association between change in GFR with baseline level of tHcy in univariate (-0.26 mL/min/y per 1-SD unit increase in tHcy level; 95% confidence interval [CI], -0.67 to 0.15) or multivariable (-0.18 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.53 to 0.17) analysis in study A or univariate (0.07 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.36 to 0.51) or multivariable (0.24 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.16 to 0.64) analysis in study B. Similarly, higher cysteine levels and lower B vitamin levels were not associated with faster rates of GFR decline in multivariable analysis in either study.. Higher tHcy or cysteine levels and lower folate, PLP, and vitamin B12 levels are not independent risk factors for progression of nondiabetic kidney disease.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Biomarkers; Blood Pressure Monitoring, Ambulatory; Cysteine; Diet, Protein-Restricted; Disease Progression; Female; Folic Acid; Homocysteine; Humans; Kidney Diseases; Male; Middle Aged; Prognosis; Pyridoxal Phosphate; Risk Factors; Vitamin B 12

The possible role of folate supplementation in reducing hyperhomocysteinemia in dialysis patients has been reported in several recent papers. However, scant data are available for peritoneal dialysis patients; besides, none of these studies investigated either the role of intraerythrocyte folate concentration or the presence of side effects caused by folate administration. Sixty-six peritoneal dialysis patients with hyperhomocysteinemia (>15 micromol/l) and normal folate status (as assessed by erythrocyte folate level >600 nmol/l) were randomly allocated to receive either oral folate (5 mg/day) or no vitamin supplementation. After 2 months of therapy, patients were requested to answer a questionnaire investigating the occurrence of symptoms possibly related to folate supplementation. Twenty-nine treated patients and 30 untreated controls completed the study. In the treated patients, serum and erythrocyte folate increased significantly (p < 0.0001) (respectively from 10.6 +/- 4.9 to 237 +/- 231 nmol/l and from 1,201 +/- 297 to 2,881 +/- 294 nmol/l) to levels at the uppermost limit of detection by laboratory methods. Serum vitamin B(12) levels did not change. Plasma homocysteine levels decreased from 54 +/- 32 to 23 +/- 14 micromol/l after folate supplementation and remained unchanged in the control group. After 4 months of folate therapy, homocysteine concentration was within the normal range in 5 patients (17%) and below 30 micromol/l in the other 21 (72%). Folate therapy resulted in a decrease in homocysteine of more than 50% in 45% of the patients and decrease of more than 20% in a further 38%. No significant symptoms were reported. Thus, serum and erythrocyte folate increase confirms that normal folate levels are inadequate in dialysis patients, even if serum and erythrocyte levels before folate supplementation cannot predict the effect on homocysteine plasma levels.

Topics: Anorexia; Depression; Down-Regulation; Erythrocytes; Female; Folic Acid; Homocysteine; Humans; Kidney Diseases; Male; Middle Aged; Peritoneal Dialysis; Sleep Initiation and Maintenance Disorders; Vitamin B 12

Topics: Cobalt Isotopes; Coenzymes; Humans; Hydroxocobalamin; Kidney Diseases; Liver Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Methotrexate is used for cure of many cancer types. It has many side effects. For this reason, obtaining a nephroprotective agent is obligatory. In the study, our aim is to determine probable effects of Vitamin B12 on MTX caused kidney damages in rats. Rats were randomly divided into 4 groups, including 8 animals in each group. Control group, VitB12 group (3 μg-kg-ip B12 throughout 15 days), MTX group (at the 8th day of experiment, a single dose of 20 mg-kg-ip MTX), Vit B12 + MTX group (3 μg-kg-ip B12 throughout 15 days and at the 8th day of experiment, a single dose of 20 mg-kg-ip MTX) Animals were anesthetized and kidney tissues were removed to evaluate biochemically, immunohistochemically and histopathologycally. There were histopathological deteriorations, rises of apoptotic cells, expressions of heat shock proteins, endoplasmic reticulum stress and inflammation markers in the MTX group. In the MTX group, Superoxide Dismutase (SOD), Total Antioxidant Status (TAS) and Catalase (CAT) levels decreased, but Total Oxidant Status TOS, Malondialdehyde (MDA) and interleukin-6 (IL6) levels increased. In addition, there was amelioration in kidney tissue in Vit B12 + MTX group compared to the MTX group. We suggest that Vit B12 can be used to reduce the toxic effects of MTX.

Topics: Animals; Antimetabolites, Antineoplastic; Apoptosis; Catalase; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; In Situ Nick-End Labeling; Interleukin-6; Kidney Diseases; Male; Malondialdehyde; Methotrexate; Rats; Rats, Wistar; Superoxide Dismutase; Vitamin B 12; Vitamin B Complex

Tamoxifen (TAMO) is a chemotherapeutic drug used for the treatment of breast cancer. Nevertheless, there is a lack of information available in regarding its nephrotoxicity. The purpose of this work was to investigate the impact of cyanocobalamin (COB) and/or calcitriol (CAL) injections on TAMO-induced nephrotoxicity.. Animals were allocated into five groups as follows: normal control group; TAMO (45 mg/kg) administered group; TAMO+COB (6mg/kg, i.p) treated group; TAMO+CAL (0.3 μg/kg, i.p) treated group; TAMO+COB+CAL combination groups.. Renal injury induced by TAMO was confirmed by the alteration in renal function parameters in the serum (urea and creatinine), as well as in the urine (creatinine clearance, total protein and albumin). These results were supported by histopathological examination. Upregulation of renal inflammatory parameters; tumor necrosis factor (TNF)-α, interleukin (IL)-6, C-reactive protein (CRP); and transforming growth factor (TGF)-β1 as well as in protein expression of nuclear factor-kappa B (NF-κB) and cleaved caspase-3 were observed to a greater extent in the TAMO-treated rats compared with the control. Renal fibrosis was also evidenced by a elevation in renal L-hydroxyproline level as well as by histomorphological collagen deposition in TAMO-treated groups compared to the control group. Administration of COB and/or CAL concurrently with TAMO significantly ameliorated the deviation in the above-studied parameters and improved the histopathological renal picture.. Inhibition of NF-κβ-mediated inflammation and caspase-3-induced apoptosis are possible renoprotective mechanisms of COB and/or CAL against TAMO nephrotoxicity, which was more noticeable in the TAMO group treated with the combination of the two vitamins in question.

Topics: Acute Kidney Injury; Animals; Apoptosis; Blood Urea Nitrogen; Calcitriol; Caspase 3; Creatinine; Female; Kidney; Kidney Diseases; Kidney Function Tests; Nephritis; NF-kappa B; Rats; Rats, Wistar; Signal Transduction; Tamoxifen; Tumor Necrosis Factor-alpha; Vitamin B 12

Topics: Alcoholism; Hematologic Neoplasms; Hospital Departments; Hospitalization; Humans; Kidney Diseases; Liver Diseases; Prospective Studies; Vitamin B 12

Classical (or isolated) methylmalonic acidemia (MMA) is a heterogeneous inborn error of metabolism most typically caused by mutations in the vitamin B12-dependent enzyme methylmalonyl-CoA mutase (MUT). With the improved survival of individuals with MMA, chronic kidney disease has become recognized as part of the disorder. The precise description of renal pathology in MMA remains uncertain.. Light microscopy, histochemical, and ultrastructural studies were performed on the native kidney obtained from a 19-year-old patient with mut MMA who developed end stage renal disease and underwent a combined liver-kidney transplantation.. The light microscopy study of the renal parenchyma in the MMA kidney revealed extensive interstitial fibrosis, chronic inflammation, and tubular atrophy. Intact proximal tubules were distinguished by the widespread formation of large, circular, pale mitochondria with diminished cristae. Histochemical preparations showed a reduction of cytochrome c oxidase and NADH activities, and the electron microscopy analysis demonstrated loss of cytochrome c enzyme activity in these enlarged mitochondria.. Our results demonstrate that the renal pathology of MMA is characterized by megamitochondria formation in the proximal tubules in concert with electron transport chain dysfunction. Our findings suggest therapies that target mitochondrial function as a treatment for the chronic kidney disease of MMA.

Topics: Amino Acid Metabolism, Inborn Errors; Atrophy; Diet, Protein-Restricted; Female; Humans; Kidney; Kidney Diseases; Kidney Tubules, Proximal; Metabolism, Inborn Errors; Methylmalonyl-CoA Mutase; Mitochondria; Mitochondrial Diseases; Nephritis; Vitamin B 12; Young Adult

Topics: Aged, 80 and over; Anemia; Female; Ferritins; Folic Acid; Glomerular Filtration Rate; Hemoglobins; Humans; Kidney Diseases; Male; Malnutrition; Retrospective Studies; Sex Factors; Vitamin B 12

Vitamin B₁₂ deficiency is common among the elderly, and early detection is clinically important. However, clinical signs and symptoms have limited diagnostic accuracy and there is no accepted reference test method.. In elderly subjects (n = 700; age range 63-97 years), we investigated the ability of serum cobalamin, holotranscobalamin (holoTC), total homocysteine (tHcy), methylmalonic acid (MMA), serum and erythrocyte folate, and other hematologic variables to discriminate cobalamin deficiency, defined as red blood cell cobalamin <33 pmol/L.. Serum holoTC was the best predictor, with area under the ROC curve (95% CI) 0.90 (0.86-0.93), and this was significantly better (P ≤ 0.0002) than the next best predictors; serum cobalamin, 0.80 (0.75-0.85), and MMA, 0.78 (0.72-0.83). For these 3 analytes, we constructed a 3-zone partition of positive and negative zones and a deliberate indeterminate zone between. The boundaries were values of each test that resulted in a posttest probability of deficiency of 60% and a posttest probability of no deficiency of 98%. The proportion of indeterminate observations for holoTC, cobalamin, and MMA was 14%, 45%, and 50%, respectively. Within the holoTC indeterminate zone (defined as 20-30 pmol/L), discriminant analysis selected only erythrocyte folate, which correctly allocated 65% (58/89) of the observations. Renal dysfunction compromised the diagnostic accuracy of MMA but not holoTC or serum cobalamin.. This study supports the use of holoTC as the first-line diagnostic procedure for vitamin B₁₂ status.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Discriminant Analysis; Erythrocytes; Female; Folic Acid; Homocysteine; Humans; Kidney Diseases; Kidney Function Tests; Linear Models; Male; Methylmalonic Acid; Middle Aged; Predictive Value of Tests; Reference Values; ROC Curve; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

Anaemia in the very elderly is usually dissected to a variety of root causes. The frequency of nutritional anaemias is particularly uncertain, since there is controversy on the real prevalence of folate, vitamin B12 and iron deficiencies, as well as on their potential pathophysiological relationship with anaemia.. We retrospectively analysed results of haemoglobin, ferritin, folate and vitamin B12 measurements performed on a cohort of unselected subjects over 85 years old who were referred by general practitioners for routine diagnostic check-up to our laboratory over the past 2 years. Furthermore, glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) formula.. The overall prevalence of nutritional deficiencies was low in males (<25%) and very low in females (<15%). Significant differences between anaemic and non-anaemic subjects were observed only for GFR in both males (44+/-3 versus 67+/-3 mL/min/1.73 m(2); p=0.035) and females (42+/-3 versus 61+/-3 mL/min/1.73 m(2); p=0.019). Likewise, a significantly difference in the frequency of anaemic and non-anaemic subjects with values below the conventional thresholds of the parameters tested was observed only for GFR in both males (59 versus 14%; p<0.001) and females (61 versus 41%; p<0.001), and for ferritin in females (15 versus 5%; p<0.001). In multiple linear regression analysis haemoglobin values were significantly associated only with GFR (both in men and women).. The results of this study suggest that impaired renal function might be the major determinant of anaemia in the very elderly. Accordingly, the cost-effectiveness of screening for nutritional deficiencies in older individuals is doubtful, since it would be associated with substantial expenditure and limited diagnostic efficiency.

Topics: Aged, 80 and over; Anemia; Female; Ferritins; Folic Acid; Glomerular Filtration Rate; Hemoglobins; Humans; Kidney Diseases; Male; Malnutrition; Retrospective Studies; Sex Factors; Vitamin B 12

Topics: Health Knowledge, Attitudes, Practice; Homocysteine; Humans; Kidney Diseases; Vitamin B 12

Dysfunction of proximal tubules resulting in tubulointerstitial nephritis and chronic renal failure is a frequent long-term complication of methylmalonic acidurias. However, the underlying pathomechanisms have not yet been extensively studied owing to the lack of suitable in vitro and in vivo models. Application of hydroxycobalamin[c-lactam] has been shown to inhibit the metabolism of hydroxycobalamin and, thereby, to induce methylmalonic aciduria in rats, oligodendrocytes, and rat hepatocytes. Our study characterizes the biochemical and bioenergetic effects of long-term exposure of human proximal tubule cells to hydroxycobalamin[c-lactam], aiming to establish a novel in vitro model for the renal pathogenesis of methylmalonic acidurias. Incubation of human proximal tubule cells with hydroxycobalamin[c-lactam] and propionic acid resulted in a strong, time-dependent intra- and extracellular accumulation of methylmalonic acid. Bioenergetic studies of respiratory chain enzyme complexes revealed an increase of complex II-IV activity after 2 weeks and an increase of complex I and IV activity as well as a decrease of complex II and III activity after 3 weeks of incubation. In addition, human proximal tubule cells displayed reduced glutathione content after the exposure to hydroxycobalamin[c-lactam] and propionic acid.

Topics: Amino Acid Metabolism, Inborn Errors; Animals; Cells, Cultured; Electron Transport; Glutathione; Humans; Kidney Diseases; Kidney Tubules, Proximal; Methylmalonic Acid; Propionates; Time Factors; Vitamin B 12

Topics: Endothelium, Vascular; Humans; Hyperhomocysteinemia; Kidney Diseases; Leucovorin; Renal Dialysis; Stroke; Tetrahydrofolates; Vitamin B 12; Vitamin B 6

The purpose of this study was to determine whether adjustment for renal function eliminates the relationship between total plasma homocysteine (tHcy) and vascular risk, assessed by carotid intima medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery.. We used cross-sectional data from 173 stroke patients treated with B-vitamins (folic acid 2 mg, vitamin B(6) 25 mg, and vitamin B(12) 0.5 mg) or placebo in a randomized double-blinded trial to test the relationships between posttreatment tHcy, cystatin C (a marker of glomerular filtration rate), estimated glomerular filtration rate (eGFR, Modification of Diet in Renal Disease equation) creatinine, CIMT, and FMD in stepwise and multivariable regression models. The strong linear relationship between tHcy and cystatin C was not altered by long-term B-vitamin treatment. tHcy lost significance as a predictor of the vascular measurements after adjustment for any single marker of renal function. Cystatin C, but not tHcy, was a significant independent predictor of FMD after adjustment for age, sex, smoking, systolic blood pressure, high-density lipoprotein cholesterol, and treatment group.. Adjusting for renal function eliminates the relationship between tHcy and CIMT and FMD, supporting the hypothesis that elevated tHcy is a marker for renal impairment rather than an independent cardiovascular risk factor.

Topics: Aged; Aged, 80 and over; Biomarkers; Brachial Artery; Cardiovascular Diseases; Carotid Arteries; Cross-Sectional Studies; Cystatin C; Cystatins; Female; Folic Acid; Follow-Up Studies; Glomerular Filtration Rate; Homocysteine; Humans; Kidney Diseases; Male; Middle Aged; Predictive Value of Tests; Regional Blood Flow; Regression Analysis; Risk Factors; Vitamin B 12; Vitamin B 6

Topics: Animals; Arginine; Cardiovascular Diseases; Cystatin C; Cystatins; Disease Models, Animal; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Diseases; Risk Factors; Vitamin B 12; Vitamin B 6

Vitamin B(12) deficiency and renal impairment are common in the aged, and therefore the screening test for vitamin B(12) deficiency should not be affected by renal function. Renal impairment has been associated with increased concentrations of plasma total homocysteine and methylmalonic acid, as well as increased total vitamin B(12) and holotranscobalamin concentrations.. The effect of renal impairment on vitamin B(12)-related biochemical variables was assessed in 1011 aged subjects.. Renal function as indicated by serum cystatin C correlated strongly with plasma total homocysteine (r(s)=0.53, p<0.001) and serum methylmalonic acid (r(s)=0.27, p<0.001), but not with serum total vitamin B(12) (r(s)=-0.04, p=0.227) or holotranscobalamin (r(s)=-0.01, p=0.817).. Either total vitamin B(12) or holotranscobalamin rather than homocysteine or methylmalonic acid should be used when screening an aged population prone to renal impairment.

Topics: Aged; Aged, 80 and over; Homocysteine; Humans; Kidney Diseases; Methods; Methylmalonic Acid; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

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

S-Adenosylhomocysteine (SAH) is the metabolic precursor of all the homocysteine (Hcy) produced in the body. It is formed by the enzyme SAH hydrolase in a reversible reaction. In a previous study we have shown that plasma SAH is a more sensitive indicator of the risk for cardiovascular disease, and in a second study involving patients with renal disease, we also showed that it is a more sensitive indicator of renal insufficiency than plasma Hcy. However, in the latter study, the patients with renal disease were older and had a variety of other diseases such as diabetes and primary hypertension, which are associated with vascular disease and which could reduce renal function by involvement of the kidneys. Our objective was to rule out these complicating factors as the cause of the elevated SAH in renal disease and determine whether renal insufficiency alone was the cause of the elevated SAH. We therefore measured SAH, Hcy, folate, and vitamin B12 in 23 patients between the ages of 1 and 18 years with a wide range of renal function, but who had none of these complicating factors. Glomerular filtration rate (GFR) was calculated using serum creatinine according to the Schwartz formula. None of the children were deficient in folate or vitamin B12. After adjusting for age, folate, and vitamin B12, there was a modest and insignificant decrease of 0.033 micromol/L of Hcy associated with an increase of 1 mL/min of GFR (95% confidence interval, -0.066 to 0.0002). However, there was a strong and statistically significant association between log(SAH) and log(GFR): P < .0005, R2 = 0.76. This result suggests that plasma SAH rather than Hcy is the metabolite primarily affected in renal disease. We suggest that plasma Hcy elevations that have been linked to vascular disease may be due to elevated SAH resulting from renal insufficiency.

Topics: Adolescent; Child; Child, Preschool; Congenital Hypothyroidism; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Infant; Kidney Diseases; S-Adenosylhomocysteine; Vitamin B 12

Currently, no evidence is available on the putative associations between a novel single nucleotide polymorphism of the 5,10-methylenetetrahydrofolate reductase gene MTHFR 1793G>A and plasma levels of vitamin B(12), folate, or total homocysteine (tHcy).. In a cross-sectional study of 730 kidney allograft recipients, patients were categorized by MTHFR 1793G>A genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B(12), folate, and tHcy plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of MTHFR 1793G>A and these three dependent variables. As hypothesized in previous work, we specifically evaluated possible effect modification between the MTHFR 1793G>A and 1298A>C mutations on these outcomes.. The allele frequency for MTHFR 1793G>A was 0.052. Heterozygosity (N= 72) or homozygosity (N= 2) for MTHFR 1793G>A was not independently associated with plasma levels of vitamin B(12) (P= 0.33) or tHcy (P= 0.70), but a borderline association with higher folate concentrations was detected (Deltafolate = 1.91 nmol/L) (95% CI -0.03 to 3.86 nmol/L) (P= 0.05). Further, we found strong and significant positive interactions between the MTHFR 1793G>A and 1298A>C mutations on vitamin B(12) concentrations.. Higher folate concentrations in kidney transplant recipients with MTHFR 1793GA or 1793AA and markedly higher concentrations of vitamin B(12) in patients with combined MTHFR 1793G>A and 1298A>C mutations may contribute to the survival advantage that has been postulated for such patients showing these genotypes.

Topics: Adult; Aged; Alleles; Cross-Sectional Studies; Female; Folic Acid; Genotype; Homocysteine; Humans; Kidney Diseases; Kidney Transplantation; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Single Nucleotide; Treatment Outcome; Vitamin B 12

Rates of renal and cardiovascular disease are high among Aboriginal Australians living in remote communities. Nutritional problems, in particular low folate levels, are also common. This suggests that increased homocysteine concentrations might be widespread, and a possible contributor to the high rates of cardiovascular disease.. To examine homocysteine concentrations, and their relationships to folate levels, and to markers of renal disease and cardiovascular disease in a remote Aboriginal Australian community. As part of a cross-sectional survey among adults in one community, homocysteine concentrations, concentrations of the crucial determinants (red blood cell (RBC) folate, vitamin B(12) and the C677T methylene tetrahydrofolate reductase polymorphism) and cardiovascular risk factors were examined.. Among 221 people, geometric mean homocysteine concentration was 11.8 micromol/L (range: 11.1-12.5 micromol/L), with 57/221 (26%) values > or =15.0 micromol/L. Higher concentrations were associated with older age, male gender, lower RBC folate and lower vitamin B(12) concentrations and homozygosity for C677T. Homocysteine concentrations were not related to the presence of albuminuria, other than over the overt albuminuria range. Homocysteine concentrations were inversely correlated with calculated glomerular filtration rate (GFR). Carotid intima-media thickness, however, was not related to homocysteine concentration. In multivariate analyses, age, male gender, lower RBC folate concentrations, lower vitamin B(12) concentrations, lower calculated GFR and the C677T polymorphism were all associated with homocysteine concentrations.. Homocysteine concentrations were consistent with previous limited reports in Aboriginal communities. Although superficially they are similar to reports from non-Aboriginal settings, the younger age of this cohort and the association of homocysteine concentrations with age suggest that age-specific concentrations are higher among Aboriginal Australians. In addition to dietary determinants, the high prevalence of apparently reduced renal function renal disease appears to be an important determinant of homocysteine concentrations in remote Aboriginal communities. The role of homocysteine concentrations as a potential mediator of the high rates of cardiovascular disease remains to be determined.

Topics: Adult; Albuminuria; Arteriosclerosis; Australia; Cardiovascular Diseases; Cross-Sectional Studies; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Kidney Diseases; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Native Hawaiian or Other Pacific Islander; Polymorphism, Genetic; Regression Analysis; Rural Population; Vitamin B 12

The prevalence of a sub-clinical functional vitamin B12 deficiency in the general population is higher than previously expected. Total serum vitamin B12 may not reliably indicate vitamin B12 status. To get more specificity and sensitivity in diagnosing vitamin B12 deficiency, the concept of measuring holotranscobalamin II (holoTC), a sub-fraction of vitamin B12, has aroused great interest. HoloTC as a biologically active vitamin B12 fraction promotes a specific uptake of its vitamin B12 by all cells. In this study we investigated the diagnostic value of storage (holoTC) of vitamin B12 and functional markers (methylmalonic acid (MMA)) of vitamin B12 metabolism in populations who are at risk of vitamin B12 deficiency.. Our study included 93 omnivorous German controls, 111 German and Dutch vegetarian subjects, 122 Syrian apparently healthy subjects, 127 elderly Germans and finally 92 German pre-dialysis renal patients. Serum concentrations of homocysteine (Hcy) and MMA were measured by gas chromatography-mass spectrometry, folate and vitamin B12 by chemiluminescence immunoassay, and holoTC by utilizing a RIA test.. High Hcy (>12 micromol/l), high MMA (>271 nmol/l) resp. low holoTC (vitamin B12) in serum were detected in 15%, 8% resp. 13% (1%) of German controls, 36%, 60%, resp. 72% (30%) of vegetarians, 42%, 48% resp. 50% (6%) of Syrians, 75%, 42%, resp. 21% (7%) of elderly subjects and 75%, 67% resp. 4% (2%) of renal patients. The lowest median levels of holoTC were observed in vegetarians, followed by the Syrian subjects (23 and 35 pmol/l, respectively). Renal patients had significantly higher levels of holoTC compared to the German controls (74 vs. 54 pmol/l). In the vitamin B12 range between 156 pmol/l (conventional cut-off level) and 241 pmol/l, both mean concentrations of holoTC and MMA were in the pathological range. HoloTC was the earliest marker for vitamin B12 deficiency followed by MMA. Vitamin B12 deficiency causes folate trapping. A higher folate level is required to keep Hcy normal. The relationship between MMA and holoTC seemed dependent on renal function. In renal patients with a glomerular filtration rate below 36 ml/min, a significantly lower mean level of MMA was detected within the highest tertile of holoTC concentration, compared to the lowest tertile. Thus, in renal patients, a higher serum concentration of circulating holoTC is required to deliver sufficient amounts of holoTC into the cells.. Our data support the concept that the measurement of holoTC and MMA provides a better index of cobalamin status than the measurement of total vitamin B12. HoloTC is the most sensitive marker, followed by MMA. The use of holoTC and MMA enables us to differentiate between storage depletion and functional vitamin B12 deficiency. Renal patients have a higher requirement of circulating holoTC. In renal dysfunction, holoTC cannot be used as a marker of vitamin B12 status.

Topics: Adult; Aged; Aged, 80 and over; Aging; Biomarkers; Diet, Vegetarian; Female; Folic Acid; Germany; Homocysteine; Humans; Kidney Diseases; Male; Methylmalonic Acid; Middle Aged; Risk; Syria; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

In previous studies a high frequency of elevated plasma tHcy concentrations has been observed in psychogeriatric patients (40-50%), but the main cause of these increased concentrations could not be established with certainty. Impaired renal function could partly contribute to elevated plasma tHcy concentrations in psychogeriatric patients. Therefore, in the present study, cystatin C was used as a sensitive marker for glomerular filtration. A linear regression analysis including age, blood folate, serum cobalamin, serum cystatin C and serum creatinine showed that only serum creatinine (p<0.001) and blood folate (p<0.001) independently predicted plasma tHcy concentration. However, about 44% of the patients with elevated plasma tHcy concentrations had signs of reduced glomerular filtration rate, as judged by increased serum cystatin C, whereas only about 13% of the patients with normal concentrations of plasma tHcy had signs of reduced glomerular filtration rate. This finding indicates that renal impairment may to some extent contribute to the elevated plasma tHcy concentration, even though serum cystatin C did not independently predict plasma tHcy concentration.

Topics: Age Factors; Aged; Creatinine; Cystatin C; Cystatins; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Diseases; Male; Mental Disorders; Predictive Value of Tests; Vitamin B 12

The prevalence of the methionine synthase (MTR) 2756A-->G polymorphism among individuals with severely elevated total homocysteine (tHcy) plasma levels is unknown. Therefore, 1,716 subjects, including 415 hemodialysis patients, 179 peritoneal dialysis patients, 733 kidney graft recipients, and 389 healthy subjects, were investigated. The distribution of MTR 2756A-->G, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T/1298A-->C, genotypes among study participants with extremely high tHcy plasma levels (>90th percentile) was compared with the genotype distribution of subjects with very low tHcy plasma levels (<10th percentile). The prevalence of MTR 2756AG and GG genotypes alone did not differ between individuals with extremely high or extremely low tHcy levels (P = 0.7402; odds ratio [OR], 1.076; 95% confidence interval [CI], 0.697 to 1.662). Conversely, combined MTR and MTHFR genotypes (MTR 2756AG and 2756GG and MTHFR 677TT/1298AA and 677CT/1298AC) were found more often in the highest (n = 34) compared with the lowest plasma tHcy decile (n = 19; P = 0.0252; OR, 1.983; 95% CI, 1.079 to 3.643). The number of patients with the wild-type MTR and MTHFR genotype was three times greater in the lowest compared with the highest decile (17 versus 6 patients, respectively; P = 0.0155; OR, 0.330; 95% CI, 0.126 to 0.861). In summary, our study shows that the 2756A-->G transition of MTR in combination with MTHFR 677TT/1298AA and 677CT/1298AC can be associated with extremely high tHcy plasma levels.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Adult; Aged; DNA; Female; Folic Acid; Gene Frequency; Genotype; Homocysteine; Humans; Kidney Diseases; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Peritoneal Dialysis; Point Mutation; Polymorphism, Restriction Fragment Length; Renal Dialysis; Vitamin B 12

Conflicting data have been reported concerning the independent association between proteinuria and plasma total homocysteine (tHcy) levels, particularly among chronic renal disease (CRD) patients with a normal range serum creatinine. Studies of this potential relationship have been limited by failure to assess true GFR, failure to assess proteinuria in a quantitative manner, or arbitrary restriction of the range of proteinuria examined. We examined the potential independent relationship between plasma tHcy levels and a wide range of quantitatively determined proteinuria (i.e., 0.000-8.340 g/day), among 109 CRD patients with a normal range serum creatinine (range; 0.8-1.5 mg/dl; median=1.2 mg/dl). Glomerular filtration rate (GFR) was directly assessed by iohexol clearance, and plasma status of folate, pyridoxal 5'-phosphate, and B12, along with serum albumin, were also determined. Linear modeling with ANCOVA revealed that proteinuria was not independently associated with tHcy levels (partial R=0.127; P=0.201), after adjustment for potential confounding by GFR (partial R=0.408; P<0.001), age, sex, plasma B-vitamin status, and serum albumin. Moreover, descending across quartiles (Q) [from Q4 to Q1] of GFR, ANCOVA-adjusted (i.e., for age, sex, and folate status) geometric mean tHcy levels (micromol/l) were significantly increased: tHcy Q4 GFR=9.6; tHcy Q3 GFR=10.5; tHcy Q2 GFR=11.9; tHcy Q4 GFR=14.5; P<0.001 for overall Q difference. We conclude that across a broad spectrum of quantitatively determined proteinuria, after adjustment for true GFR, in particular, there is no independent relationship between proteinuria and tHcy levels among CRD patients with a normal range serum creatinine.

Topics: Adult; Aged; Chronic Disease; Creatinine; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Proteinuria; Pyridoxal Phosphate; Serum Albumin; Vitamin B 12

We determined the vitamin B12 clearance using an ultrafiltration technique and assessed whether the clearance of this vitamin B12 could be used to estimate the glomerular filtration rate (GFR). Fourteen subjects (5 had renal disease, 7 had diabetes mellitus, one had liver cirrhosis and one had cholelithiasis) divided into two groups were studied (group 1, 5 patients without vitamin B12 preloading; group 2, 9 patients with vitamin B12 preloading). Vitamin B12 clearance was significantly correlated with inulin clearance (r = 0.81, p < 0.001) in group 1; group 2 showed an even better correlation (r = 0.94, p < 0.001) with the presaturated vitamin B12 binding protein. In group 2, the mean inulin and vitamin B12 clearance values do not differ significantly (40.3 +/- 13.6 vs 48.2 +/- 17.2 ml/min), but there was a significant difference between mean inulin and creatinine clearance (40.3 +/- 13.6 vs 64.9 +/- 19.9 ml/min, p < 0.05). In conclusion, vitamin B12 clearance appears to be a more reliable method of estimating GFR than creatinine clearance.

Topics: Adult; Aged; Cholelithiasis; Creatinine; Diabetes Mellitus; Female; Glomerular Filtration Rate; Humans; Inulin; Kidney Diseases; Liver Cirrhosis; Male; Metabolic Clearance Rate; Middle Aged; Ultrafiltration; Vitamin B 12

A nonisotopic assay of vitamin B-12 in human serum or plasma is described, performed with the Abbott IMx analyzer. The sample is first treated at pH > 12.5 to release bound vitamin B-12 and to convert all forms to cyanocobalamin. Next, the analyte is bound, at lower pH, by vitamin B-12-specific binding protein, immobilized to a solid phase of polymeric microspheres. Detection involves monitoring the activity of the tracer enzyme (alkaline phosphatase) coupled to a derivative of cyanocobalamin. Total assay precision is 7.9% for vitamin B-12 at 200 ng/L, 6.6% at 400 ng/L, and 6.7% at 800 ng/L. Assay sensitivity, calculated as 2 SD from the zero calibrator, is 37 (+/- 9) ng/L. The dynamic range extends to 2000 ng/L. Analytical recovery of 300 and 600 ng/L additions of vitamin B-12 to sera with basal concentrations of 30-400 ng/L was 102.5%. Results of the assay correlated well with those of commercially available radioisotope assays. No interference was observed in specimens from patients with pernicious anemia, chronic or acute myelogenous leukemia, or renal failure. Cross-reactivity with cobinamide (1 g/L) was < 0.00003%. Vitamin B-12 measurements for blood specimens drawn into serum, EDTA, or heparinized plasma-collection tubes agreed within 3%.

Topics: Anemia, Pernicious; Animals; Autoanalysis; Humans; Hydrogen-Ion Concentration; Intrinsic Factor; Kidney Diseases; Leukemia, Myeloid, Acute; Quality Control; Swine; Vitamin B 12

A new reverse-phase high-performance liquid chromatographic (HPLC) procedure has been developed for the quantitation of vancomycin and its crystalline degradation product, CDP-1. The new HPLC procedure involves a liquid-liquid extraction pretreatment procedure and an HPLC internal standard, vitamin B12. The new HPLC procedure was used to measure 50 renally impaired patient samples. Samples were than analyzed by the monoclonal antibody Emit vancomycin assay, and the polyclonal antibody fluorescence polarization immunoassay (FPIA) vancomycin assay, and the results were compared. The Emit vancomycin assay correlated well with HPLC, but FPIA quantitated higher than Emit and HPLC. We conclude that the polyclonal antibody FPIA assay detects CDP-1 in the samples of renally impaired patients, accounting for an average of 10% of the FPIA/Emit bias, and should therefore be used with caution when monitoring vancomycin levels in renally impaired patients.

Topics: Chromatography, High Pressure Liquid; Fluorescence Polarization Immunoassay; Humans; Immunoenzyme Techniques; Kidney Diseases; Vancomycin; Vitamin B 12

1. Addition of supplemental choline to a biotin-deficient diet decreased the biotin status of chicks and increased mortality from fatty liver and kidney syndrome (FLKS). 2. Mortality was also increased by dietary supplementation with a mixture of other B-vitamins, excluding biotin, and was highest when the choline and B-vitamin supplements were combined. 3. The occurrence of sudden death syndrome (SDS) was unaffected by dietary biotin concentration. 4. A previously unreported condition was observed in which birds died showing post-mortem signs characteristic of both FLKS and SDS and whose occurrence was related to the biotin status of the chicks.

Topics: Animals; Biotin; Chickens; Choline; Death, Sudden; Diet; Fatty Liver; Female; Kidney Diseases; Male; Poultry Diseases; Pyruvate Carboxylase; Syndrome; Vitamin B 12

The prevalence and causes of anemia have been studied in 104 patients over 60 years of age admitted to a general medical ward in Jerusalem. In males and females, mean hemoglobin levels were about 1 g less than in the corresponding groups of healthy younger controls. A primary nutritional anemia could not be implicated in any of the 15 patients with hemoglobins below 11 g/dl. The most important causes of anemia were chronic renal failure, metastatic carcinoma, gastrointestinal bleeding, and infection. Conversely, in diseases with no adverse effect on erythropoiesis such as chronic ischemic heart disease, hypertension and diabetes, hemoglobin levels were equal to those of the younger controls. These findings indicate that although diminished serum iron and RBC folate levels may occasionally be found in elderly subjects, nutritional deficiency is seldom responsible for anemia in this age group in Israel- and anemia when present is often the manifestation of a chronic underlying disease.

Topics: Adult; Aged; Anemia; Female; Folic Acid; Gastrointestinal Hemorrhage; Hemoglobins; Hospitalization; Humans; Infections; Iron; Iron Deficiencies; Israel; Kidney Diseases; Male; Middle Aged; Vitamin B 12

Topics: Child; Child, Preschool; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Radioisotope Renography; Vitamin B 12

Topics: Anemia, Pernicious; Cobalt Radioisotopes; Humans; Intestinal Absorption; Intrinsic Factor; Kidney Diseases; Malabsorption Syndromes; Methods; Time Factors; Vitamin B 12

Topics: Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Megaloblastic; Anemia, Sideroblastic; Blood Transfusion; Diet Therapy; Female; Folic Acid; Humans; Iron; Kidney Diseases; Male; Postgastrectomy Syndromes; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12

Topics: Animal Feed; Animals; Chickens; Choline; Diet; Edible Grain; Fatty Liver; Kidney; Kidney Diseases; Lipid Metabolism; Liver; Methionine; Poultry Diseases; Selenium; Syndrome; Vitamin B 12

Topics: Adult; Aged; Alcoholism; Anemia, Macrocytic; Anemia, Pernicious; Blood Cell Count; Bone Marrow Cells; Erythroplasia; Female; Folic Acid; Folic Acid Deficiency; Hematopoietic Stem Cells; Humans; Hypothyroidism; Kidney Diseases; L-Lactate Dehydrogenase; Male; Neutrophils; Nutrition Disorders; Pregnancy; Pregnancy Complications, Hematologic; Reticulocytes; Vitamin B 12

Topics: Administration, Oral; Anemia, Pernicious; Cobalt Isotopes; Crohn Disease; Female; Humans; Intestinal Absorption; Intrinsic Factor; Kidney Diseases; Malabsorption Syndromes; Male; Methods; Schilling Test; Time Factors; Vitamin B 12

Topics: Alanine Transaminase; Alkaline Phosphatase; Arthritis, Rheumatoid; Aspartate Aminotransferases; Celiac Disease; Cholesterol; Fats; Feces; Folic Acid; Humans; Kidney Diseases; Liver Function Tests; Malabsorption Syndromes; Nucleotidases; Rheumatic Diseases; Serum Albumin; Sulfobromophthalein; Vitamin B 12; Xylose

Topics: Anabolic Agents; Blood Cell Count; Blood Transfusion; Bone Marrow; Bone Marrow Diseases; Bone Marrow Examination; Bone Marrow Transplantation; Chemical and Drug Induced Liver Injury; Child, Preschool; Chloramphenicol; Female; Folic Acid; Hematopoiesis; Humans; Kidney Diseases; Methenolone; Penicillin G; Prednisolone; Vitamin B 12

Topics: Aminohippuric Acids; Blood Flow Velocity; Diuresis; Glomerular Filtration Rate; Humans; Hypertension, Renal; Inulin; Iodopyracet; Kidney; Kidney Diseases; Kidney Function Tests; Thiosulfates; Vitamin B 12

Topics: Glomerular Filtration Rate; Humans; Injections, Intravenous; Iodohippuric Acid; Kidney; Kidney Diseases; Kidney Function Tests; Methods; Plasma; Radiography; Radioisotopes; Regional Blood Flow; Thyroid Function Tests; Time Factors; Vitamin B 12

Topics: Blood Proteins; Cachexia; Chronic Disease; Humans; Kidney Diseases; Liver Diseases; Liver Extracts; Neoplasms; Vitamin B 12

Topics: Aged; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Blood Pressure; Cholesterol; Female; Folic Acid; Hemoglobinometry; Humans; Kidney Diseases; Liver Diseases; Liver Function Tests; Male; Middle Aged; Serum Albumin; Serum Globulins; Urea; Vitamin B 12

Topics: Acute Disease; Animals; Blood Urea Nitrogen; Body Weight; Chlortetracycline; Cholesterol; Choline Deficiency; Cystine; Diet; Feces; Germ-Free Life; Hematocrit; Kidney Diseases; Lipid Metabolism; Liver; Male; Neomycin; Rats; Stimulation, Chemical; Vitamin B 12

Topics: Adolescent; Adult; Aged; Charcoal; Cobalt Isotopes; Female; Glomerular Filtration Rate; Humans; Hydroxocobalamin; Inulin; Kidney Diseases; Kidney Function Tests; Male; Methods; Middle Aged; Time Factors; Vitamin B 12

Topics: Chromium Isotopes; Cobalt Isotopes; Hematologic Diseases; Humans; Kidney Diseases; Vitamin B 12

Topics: Cobalt Isotopes; Glomerular Filtration Rate; Humans; Inulin; Iodine Radioisotopes; Kidney Diseases; Radiometry; Vitamin B 12

Topics: Adolescent; Animals; Child; Child, Preschool; Female; Hematologic Diseases; Humans; Infant; Infections; Kidney Diseases; Lactobacillus; Liver Diseases; Male; Rats; Rheumatic Fever; Vitamin B 12

Topics: Animals; Choline; Choline Deficiency; Deficiency Diseases; Kidney Diseases; Liver Diseases; Methionine; Rats; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Cobalt Isotopes; Creatine; Creatinine; Diagnosis; Glomerular Filtration Rate; Gout; Humans; Hypertension; Hypertension, Renal; Injections, Intravenous; Inulin; Kidney; Kidney Diseases; Kidney Function Tests; Uric Acid; Urine; Vitamin B 12; Vitamins

Topics: Acute Kidney Injury; Biological Assay; Blood Chemical Analysis; Glomerulonephritis; Kidney Diseases; Kidneys, Artificial; Mercury Poisoning; Nephritis; Nephritis, Interstitial; Postoperative Complications; Pyelonephritis; Renal Insufficiency; Solvents; Toxicology; Tuberculosis; Tuberculosis, Renal; Vitamin B 12; Wounds and Injuries

Topics: Anemia; Anemia, Hemolytic; Blood Protein Disorders; Brain Neoplasms; Chlormerodrin; Chromium Isotopes; Clinical Laboratory Techniques; Cobalt Isotopes; Diuretics; Erythrocytes; Heart Diseases; Hypoproteinemia; Iodine Isotopes; Kidney Diseases; Liver Diseases; Lung Diseases; Neoplasms; Obesity; Organomercury Compounds; Polycythemia; Protein Deficiency; Pulmonary Embolism; Radiation Protection; Radioisotopes; Radiometry; Radionuclide Imaging; Schilling Test; Spleen; Thinness; Thyroid Diseases; Vitamin B 12

Topics: Cobalt; Cobalt Radioisotopes; Corrinoids; Hematinics; Humans; Kidney Diseases; Vitamin B 12

Topics: Kidney Diseases; Liver Diseases; Liver Extracts; Vitamin B 12

The serum vitamin B(12) level was abnormally high in 14 out of 32 cases of renal failure. This was probably due to impaired excretion of the vitamin, but the results of measurements of the rate of excretion of radioactive vitamin B(12) did not provide unequivocal evidence on this point; other possible explanations are discussed. Renal failure must be added to the causes of high serum B(12) levels.

Topics: Arteriosclerosis; Glomerulonephritis; Humans; Hypertension; Hypertension, Malignant; Kidney; Kidney Diseases; Nephritis; Nephrocalcinosis; Polycystic Kidney Diseases; Pyelonephritis; Renal Insufficiency; Vitamin B 12

Topics: Anatomy; Androgens; Animals; Body Weight; Corrinoids; Cortisone; Incidence; Kidney Diseases; Liver Diseases; Mice; Myocardium; Necrosis; Pericarditis; Testosterone; Vitamin B 12

Topics: Corrinoids; Diabetes Mellitus; Diabetic Retinopathy; Hematinics; Humans; Kidney Diseases; Vitamin B 12

Topics: Anemia; Anemia, Pernicious; Corrinoids; Hematinics; Humans; Kidney Diseases; Vitamin B 12

Topics: Kidney Diseases; Renal Insufficiency; Vitamin B 12

Topics: Animals; Chickens; Choline; Folic Acid; Humans; Kidney; Kidney Diseases; Rats; Vitamin B 12; Vitamin B Complex

Topics: Animals; Choline; Corrinoids; Hematinics; Hemorrhage; Kidney; Kidney Diseases; Rats; Vitamin B 12