Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
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Coen van Guldener
Abstract
Hyperhomocysteinaemia almost invariably occurs in patients with end-stage renal disease (ESRD), but there is debate whether, within the group of ESRD patients, higher or lower plasma homocysteine concentrations are related to an increased risk of vascular disease. Homocysteine is thought to be vasculotoxic in high concentrations, but it may also lead to elevated levels of its precursor, S-adenosylhomocysteine (AdoHcy), which is a potent inhibitor of the transmethylation pathway, in which S-adenosylmethionine (AdoMet) donates its methyl group to a variety of acceptors. Impairment of this transmethylation pathway in ESRD patients has been suggested by high AdoHcy levels, decreased AdoMet/AdoHcy ratios, decreased protein repair requiring methyltransferases, and by DNA hypomethylation. Stable isotope techniques using labelled methionine have indeed demonstrated a decreased whole body transmethylation flux in ESRD patients. These studies have also shown that folic acid treatment is capable of restoring transmethylation rates to normal values. The remaining hyperhomocysteinaemia after folic acid treatment in ESRD is probably due to a persistent impairment of homocysteine clearance through transsulphuration. DNA hypomethylation with its concurrent alterations in gene expression is largely improved by folate treatment. The adverse effects of hyperhomocysteinaemia in ESRD may thus be related to impaired transmethylation. Normalisation of plasma homocysteine does not seem to be required to restore transmethylation to normal levels in ESRD patients.
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©2005 by Walter de Gruyter Berlin New York
Artikel in diesem Heft
- Homocysteine research – where do we stand and where are we going?
- Hyperhomocysteinemia and arteriosclerosis: historical perspectives
- Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
- Homocysteine and vascular disease in diabetes: a double hit?
- Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
- Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
- Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
- Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
- Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
- Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
- Hyperhomocysteinemia and macromolecule modifications in uremic patients
- Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
- Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
- Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
- Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
- A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
- Betaine: a key modulator of one-carbon metabolism and homocysteine status
- Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
- Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
- Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
- Homocysteine and B vitamins in mild cognitive impairment and dementia
- Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
- Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
- Homocysteine – a newly recognised risk factor for osteoporosis
- Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
- Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
- Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
- Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
- Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
- Interactions between folate and aging for carcinogenesis
- The potential cocarcinogenic effect of vitamin B12 deficiency
- The vegetarian lifestyle and DNA methylation
Artikel in diesem Heft
- Homocysteine research – where do we stand and where are we going?
- Hyperhomocysteinemia and arteriosclerosis: historical perspectives
- Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
- Homocysteine and vascular disease in diabetes: a double hit?
- Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
- Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
- Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
- Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
- Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
- Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
- Hyperhomocysteinemia and macromolecule modifications in uremic patients
- Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
- Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
- Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
- Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
- A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
- Betaine: a key modulator of one-carbon metabolism and homocysteine status
- Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
- Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
- Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
- Homocysteine and B vitamins in mild cognitive impairment and dementia
- Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
- Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
- Homocysteine – a newly recognised risk factor for osteoporosis
- Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
- Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
- Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
- Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
- Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
- Interactions between folate and aging for carcinogenesis
- The potential cocarcinogenic effect of vitamin B12 deficiency
- The vegetarian lifestyle and DNA methylation
