Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of hyperhomocysteinemia (HHcy) as a risk marker for cardiovascular diseases in renal patients is a matter of controversy. The remethylation of homocysteine (Hcy) to methionine in the kidneys is of great importance for Hcy clearance. Hcy remethylation is markedly decreased in patients on hemodialysis, but transsulfuration remains mostly unaffected. Markedly increased concentrations of methylmalonic acid (MMA), as a metabolic marker of vitamin B12 deficiency, have been found in approximately 70% of renal patients. This is in contrast to normal concentrations of vitamin B12 usually reported in such patients. We demonstrated in cell culture experiments that the uptake of vitamin B12 by mononuclear cells from renal patients was lower than that taken up by cells from controls. The lowering of MMA and Hcy concentrations in renal patients after B12 administration may indicate the presence of intracellular pre-treatment deficiency. We administered folic acid (5 mg) plus vitamin B6 (50 mg) and B12 (0.7 mg) three times per week intravenously to hyperhomocysteinemic dialysis patients. Hcy decreased after 4 weeks by 51%. Hcy was normalized in almost all patients, while serum concentrations of MMA and cystathionine were reduced by 28% and 26%, respectively. Cystathionine, an indicator for the transsulfuration pathway, showed a drastic increase in renal disease and was only slightly lowered by B-vitamin treatment. The increased cystathionine/cysteine ratio in renal patients indicates possible impairment of the catabolism of cystathionine by cystathionase. Moreover, renal failure is associated with severe abnormalities in plasma concentrations of S-adenosyl Hcy (SAH) and S-adenosyl methionine (SAM), as well as the SAM/SAH ratio. This ratio is an indicator of the availability of methyl groups from SAM. Therapeutic doses of B-vitamins in dialysis patients led to a limited improvement in the biomarkers of methylation and probably did not have a significant effect on transmethylation potential in the cells. Furthermore, elevated serum levels of asymmetric dimethylarginine (ADMA) in renal patients, which are associated with a poor outcome for such patients, could be lowered, but this effect was confined to patients who had no anemia. Future studies may consider extending the duration of vitamin treatment, as well as agents that may enhance the hydrolysis of SAH and cystathionine.
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PMID:Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients. 1619 95

Since vitamin B12 serves as a cofactor in the synthesis of methyl precursors for biological methylation and enables methylfolate to be recycled for nucleotide synthesis, B12 deficiency has been known to induce hyperhomocysteinemia and inadequate DNA synthesis, along with "methylfolate trap". Even though depletion of B12, a common B-vitamin deficiency in the elderly, has not often been invoked as a causative factor in carcinogenesis, a recent animal study demonstrated that a B12-deficient diet, which was of insufficient severity to cause anemia or illness, disturbed normal homeostasis of one-carbon metabolism in the colonic mucosa and resulted in diminished genomic DNA methylation and increased uracil misincorporation in DNA, both of which are purported mechanisms for one-carbon metabolism-related colonic carcinogenesis.
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PMID:The potential cocarcinogenic effect of vitamin B12 deficiency. 1619 14

The risk of developing cardiovascular disease is greatly increased in patients undergoing renal replacement therapy and, notably, morbidity and mortality due to therapy is much higher in these patients than in the general population. Minimal alterations in renal function, as evidenced by reduced glomerular filtration rate and the presence of albuminuria, have been described as potent cardiovascular risk factors. The classic risk factors only partly explain this difference; hence, we must admit the existence of known and emerging factors associated with increased cardiovascular risk in patients with renal disease. This article provides a review of these factors. It describes the role of hyperphosphoremia and elevated calcium-phosphorous product in the formation of cardiovascular calcifications, the contribution of anemia to left ventricular hypertrophy, and the consequences of accelerated atherogenesis with oxidative stress and a microinflammatory state resulting from endothelial dysfunction. Hyperhomocysteinemia, increased sympathetic nervous system activity, lipoprotein alterations with elevated lipoprotein A, and increases in the concentrations of asymmetrical dimethyl-arginine are other examples of the changes described in this population. Patients with renal disease should be considered to be at high risk for developing cardiovascular disease and candidates for implementation of secondary prevention strategies. It is for this reason that early identification of renal failure, which remains hidden in many cases, is of prime importance.
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PMID:Chronic renal failure: a cardiovascular risk factor. 1633 73

Intravenous iron is commonly used in conjunction with erythropoietic agents to treat anemia in patients with chronic kidney disease. Iron has been proposed to promote oxidative stress and endothelial dysfunction in vascular tissues. We studied the acute effects of intravenous iron sucrose on homocysteine-induced endothelial dysfunction in the brachial artery of normal human subjects. In all, 40 healthy subjects received intravenous iron sucrose 100 mg or placebo over 30 min immediately before ingestion of 100 mg/kg of oral methionine in a double-blind, randomized study. Flow- and nitroglycerin-mediated dilation in the brachial artery, serum markers of iron stores, and homocysteine and nitrotyrosine levels were measured before and after study drug administration. Intravenous iron significantly increased transferrin saturation and non-transferrin-bound iron (NTBI) when compared with placebo. Flow-mediated dilation significantly decreased from baseline 1 h after administration of iron sucrose when compared with placebo (from 6.66+/-0.47 to 1.93+/-0.35% after iron sucrose vs from 6.00+/-0.40 to 5.61+/-0.46% after placebo, P<0.001), but did not differ between groups at 4 h (1.10+/-0.39 vs 1.33+/-0.51%). Nitroglycerin-mediated vasodilation, and homocysteine and 3-nitrotyrosine levels did not differ after administration of iron sucrose and placebo. Intravenous administration of iron sucrose in the setting of transient hyperhomocysteinemia induced by methionine ingestion significantly increased transferrin saturation and plasma levels of NTBI and significantly attenuated flow-mediated dilation in the brachial artery when compared with placebo. This potential mechanistic link between intravenous iron and endothelial dysfunction warrants further study of cardiovascular effects of intravenous iron in anemic chronic kidney disease populations.
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PMID:Iron sucrose augments homocysteine-induced endothelial dysfunction in normal subjects. 1646 88

Atherosclerosis is a major cause of morbidity and mortality for ESRD patients and we have little knowledge about the presence and risk factors of atherosclerosis in children with CRF. The measurement of carotid artery intima-media thickness (cIMT) using high-resolution ultrasonography is suggested as an excellent marker of subclinical atherosclerosis. In this study, we aimed to investigate the presence of atherosclerosis and to determine the relationship between atherosclerosis and some risk factors in children and young adults with ESRD. Thirty-four patients with ESRD and 20 controls were included in this study. The measurement of cIMT was performed by using a linear B-mode 7.5-MHz ultrasound transducer. We determined anemia, abnormal calcium/phosphate metabolism, hyperhomocysteinemia, hypertriglyceridemia and increased lipoprotein (a) levels in the ESRD group. The cIMT in the ESRD group was higher than in the control group (P<0.05). SBP, DBP, MAP, LVMI and LVH prevalence were statistically higher in the ESRD group (P<0.05). There were significant positive correlations between cIMT and LVMI, MBP, whereas a significant negative correlation was determined between cIMT and PTH in the ESRD group (P<0.05). When a multiple linear regression analysis was performed with cIMT as a dependent variable and LVMI, MBP, PTH, as independent variables, a significant positive correlation was determined between cIMT and LVMI (P<0.05). In conclusion, we think that arteriopathy occurs in children with ESRD. Left ventricular hypertrophy and hypertension may associate with vascular changes in children and young adults with ESRD. Further investigations are necessary to explain association of LVMI index with cIMT.
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PMID:Carotid artery thickness in children and young adults with end stage renal disease. 1694 11

By the time of renal transplantation, end-stage renal disease patients have a huge burden of cardiovascular disease (CVD) and are heavily saturated with atherosclerotic risk factors. Worsening of preexisting risk factors or new CVD risk factors may develop in the posttransplant period consequent in part to the diabetogenic and atherogenic potential of immunosuppressive drugs. The annual risk of a fatal or non-fatal CVD event of 3.5 to 5% in kidney transplant recipients is 50-fold higher than the general population. Renal allograft dysfunction, proteinuria, anemia, moderate hyperhomocysteinemia and elevated serum C-reactive protein concentrations, each dependently confer greater risk of CVD morbidity and mortality in the posttransplant period. Long-term care of renal transplant recipients should programmatically incorporate the recommendations of the National Kidney Foundation Working Groups and European Best Practice Guidelines Expert Group on Renal Transplantations into the management of hypertension, dyslipidemia, smoking, and posttransplant diabetes mellitus. Timely utilization of coronary revascularization procedures should be undertaken as these treatments are equally effective in the kidney transplant population.
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PMID:Cardiovascular complications after renal transplantation and their prevention. 1696 81

Cardiovascular disease is the leading cause of death following renal transplantation, accounting for 40% to 55% of all deaths. An analysis in our center showed a 15% mortality in a cohort of renal transplant recipients followed for an average of 10 years. Various contributing risk factors of cardiovascular diseases in transplant recipients such as tobacco use, hypertension, hyperlipidemia, hereditary risk, diabetes, physical inactivity, obesity, dialysis duration, hyperuricemia, proteinuria, hyperhomocysteinemia, hyperparathyroidism, anemia; C-reactive protein level, and immunosuppressive regimen as well as some rare risk factors, such as cytomegalovirus infection, were evaluated in a population of 1200 kidney transplant recipients. Also we introduced methods for early detection, monitoring, and follow-up of proven risk factors of cardiovascular disease.
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PMID:How to decrease cardiovascular mortality in renal transplant recipients. 1711 56

The next decade will face an increase in the number of patients affected by end-stage renal disease. In line with the growing incidence of type 2 diabetes, hypertension and old age in the general population, we can expect a dramatic increase of uremic patients needing a substitutive treatment of renal function. On the basis of the current trends, we expect an exponential growth of cardiovascular complications in both dialysis and transplant populations. Progress in the treatment of end-stage renal disease will aim at the prevention of cardiovascular complications, that remain the leading cause of morbidity and mortality in uremic patients. Preventive interventions for cardiovascular complications should focus on traditional risk factors, such as hypertension, dyslipidemia and obesity, diabetes mellitus, smoking, as well as on the non traditional risk factors inherent in the uremic state, such as anemia, hyperphosphoremia, hyperhomocysteinemia, inflammation and malnutrition. Recent and future innovations in peritoneal dialysis solutions include a larger use of icodextrin, a glucose polymer able to enhance ultrafiltration while inducing less glycation and caloric absorption, and perhaps improving blood pressure control. The gene therapy directed to the mesothelial cells should bring about improvements in nutrition, cardiovascular comorbidity, and dialysis adequacy. Patients submitted to increased hemodialysis time or to the implementation of a night or daily hemodialysis program have shown better blood pressure control, cardiovascular stability, tolerability and perhaps reduced mortality. Modifications of dialysis schedules clearly indicate another road to future improvements in renal replacement therapy. In the field of kidney transplantation, much improvement has already been achieved regarding the prevention of acute rejection, and the new therapeutic strategies are aimed at reducing the incidence of the adverse reactions of immunosuppressive drugs, as well as of the chronic allograft nephropathy. Induction of transplantation tolerance remains the most attractive target, which now seems closer than before because many of the mechanisms involved in the tolerance induction have been better elucidated.
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PMID:[Perspectives on treatment of the renal failure]. 1725 35

Aim of the study was to estimate the incidence of coronary heart disease (CAD) in patients (pts) with end stage renal disease (ESRD) maintained on chronic hemodialysis (HD) and its association with the presence of predisposing factors. The study included 171 dialysis pts (107 male (M) and 64 female (F)). Mean age of pts was 67+/-13 years, mean time on dialysis 52.7+/-44 months and Body Mass Index (BMI) 25.9+/-3.7 kg/m2. Fifty pts (29.2%) were clinically diagnosed with CAD. The diagnosis was established by coronary angiography in 24 (48%) and in 26 by combined dipyridamole-exercise thallium imaging (52%). Pts' data in association with the development of CAD that were recorded included age, sex, smoking habits, hypertension, obesity, the presence of diabetes mellitus (DM), hyperlipidemia, anemia, low albumin levels, secondary hyperparathyroidism (SHP), the presence of chronic inflammation, as evidenced by the presence of elevated levels of CRP and hyperhomocysteinemia. There was a statistically significant association of increasing age and CAD (p<0.0001). Relative risk (RR) was significantly increased i) in male pts compared to female pts (RR: 8.56, p<0.001), ii) in anemic pts compared to pts with hemoglobin levels< or =11 g/dL (RR: 8.26, p<0.0001), iii) in obese pts compared to pts with BMI < or =30 (RR: 5.09, p<0.005) and iv) in pts with increased levels of homocysteine compared to pts with levels of homocysteine <15 |IM (RR: 4.14, p<0.0001). Using linear regression analysis, CAD was associated with the inadequacy of HD (r = - 0.05, p<0.0001), time on HD (r =0.04, p =0.012) and increasing age (r =0.24, p<0.001). There was no statistically significant association between CAD and the presence of the other traditional risk factors. The incidence of CAD in dialysis pts is significantly increased with age, male sex, obesity, time on dialysis, the presence of anemia, hyperhomocysteinemia and inadequacy of HD.
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PMID:Incidence and risk factors of coronary artery disease in patients on chronic hemodialysis. 1741 65

Vitamin B12 deficiency may be induced by long-term use of metformin, which may in turn lead to hyperhomocysteinemia. Thus, hyperhomocysteinemia may increase the risk of vascular thrombosis in diabetic patients, when metformin is used and a homozygous methylenetetrahydrofolate reductase (MTHFR) C677T mutation is present. We report a 65-year-old Taiwanese diabetic woman who was treated with metformin for 6 years and who had suffered from swelling of the left lower extremity for 3 months. Ascending venography confirmed the diagnosis of proximal deep vein thrombosis, while hyperhomocysteinemia, megaloblastic anemia caused by vitamin B12 deficiency, and a homozygous C677T mutation of the MTHFR gene were also found. She had no identifiable venous thrombotic risk factors other than hyperhomocysteinemia, which seemed to be caused by both MTHFR C677T homozygous mutation and vitamin B12 deficiency. With the substitution of insulin injection for metformin, short-term supplement of vitamin B12, and anticoagulant therapy for the deep vein thrombosis, her anemia and hyperhomocysteinemia recovered rapidly. The deep vein thrombosis also responded well. Our findings highly suggested the role of metformin in causing vitamin B12 deficiency, which may serve as an additional risk factor for venous thrombosis in diabetic patients. Our report also highlights the need to check vitamin B12 levels during metformin treatment.
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PMID:Hyperhomocysteinemia, deep vein thrombosis and vitamin B12 deficiency in a metformin-treated diabetic patient. 1858 23


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