Hyperhomocysteinemia in Chronic Renal Failure: Alternative Therapeutic Strategies

Perna, Alessandra F.; Sepe, Immacolata; Lanza, Diana; Pollastro, Rosa Maria; Santo, Natale G. De; Ingrosso, Diego

doi:10.1053/j.jrn.2011.10.008

Cited by 16 publications

(15 citation statements)

References 21 publications

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“…Numerous studies have demonstrated an association of HHcy with vascular disease [ 1 – 3 , 15 , 35 , 61 – 63 ], and several age related pathologies like Alzheimer’s disease [ 64 – 66 ], stroke [ 67 , 68 ], Parkinson’s disease (PD) [ 66 ] have also been linked to high levels of Hcy. Additionally there are studies showing an association between HHcy and osteoporosis [ 69 ], end stage renal disease (ESRD) [ 70 ], insulin resistance (IR) [ 71 , 72 ], aneurysm [ 73 – 75 ], hypothyroidism [ 76 , 77 ] cancer [ 78 , 79 ] and gastrointestinal disorders [ 80 ] to mention some.…”

Section: Pathologies Associated With Hcymentioning

confidence: 99%

“…The common causes known to contribute to this pathology are high blood pressure and diabetes. Chronic renal failure and uremia represent states wherein high blood levels of Hcy are seen [ 70 ], and with decline in function these patients become more and more hyperhomocysteinemic [ 93 ]. Also, an association between dialysis and an increase in plasma level of Hcy is documented [ 94 ].…”

Section: Pathologies Associated With Hcymentioning

confidence: 99%

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The metabolism and significance of homocysteine in nutrition and health

et al. 2017

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An association between arteriosclerosis and homocysteine (Hcy) was first demonstrated in 1969. Hcy is a sulfur containing amino acid derived from the essential amino acid methionine (Met). Hyperhomocysteinemia (HHcy) was subsequently shown in several age-related pathologies such as osteoporosis, Alzheimer’s disease, Parkinson’s disease, stroke, and cardiovascular disease (CVD). Also, Hcy is associated with (but not limited to) cancer, aortic aneurysm, hypothyroidism and end renal stage disease to mention some. The circulating levels of Hcy can be increased by defects in enzymes of the metabolism of Met, deficiencies of vitamins B6, B12 and folate or by feeding Met enriched diets. Additionally, some of the pharmaceuticals currently in clinical practice such as lipid lowering, and anti-Parkinsonian drugs are known to elevate Hcy levels. Studies on supplementation with folate, vitamins B6 and B12 have shown reduction in Hcy levels but concomitant reduction in certain associated pathologies have not been definitive. The enormous importance of Hcy in health and disease is illustrated by its prevalence in the medical literature (e.g. > 22,000 publications). Although there are compelling data in favor of Hcy as a modifiable risk factor, the debate regarding the significance of Hcy mediated health effects is still ongoing. Despite associations between increased levels of Hcy with several pathologies being well documented, whether it is a causative factor, or an effect remains inconclusive. The present review though not exhaustive, is focused on several important aspects of Hcy metabolism and their relevance to health.

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Section: Pathologies Associated With Hcymentioning

confidence: 99%

Section: Pathologies Associated With Hcymentioning

confidence: 99%

The metabolism and significance of homocysteine in nutrition and health

et al. 2017

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“…Hyperhomocysteinemia can result from four main disorders: 1) genetic abnormalities of enzymes involved in homocysteine metabolism, 2) nutritional deficiencies in folate, vitamin B 6 and vitamin B 12 , 3) methionine rich diet, and 4) decreased renal function. Two enzymes and three vitamins play a key role in the regulation of circulating homocysteine levels (Nagele et al 2011;Nilsson et al 2014;Iacobazzi et al 2014;Cook and Hess 2005;Perna et al 2012).…”

Section: Basic Mechanisms In Development Of Hyperhomocysteinemiamentioning

confidence: 99%

Homocysteine and homocysteine-related compounds: an overview of the roles in the pathology of the cardiovascular and nervous systems

Djuric

Jakovljević

Živković

et al. 2018

Can. J. Physiol. Pharmacol.

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Homocysteine, an amino acid containing a sulfhydryl group, is an intermediate product during metabolism of the amino acids methionine and cysteine. Hyperhomocysteinemia is used as a predictive risk factor for cardiovascular disorders, the stroke progression, screening for inborn errors of methionine metabolism, and as a supplementary test for vitamin B deficiency. Two organic systems in which homocysteine has the most harmful effects are the cardiovascular and nervous system. The adverse effects of homocysteine are achieved by the action of several different mechanisms, such as overactivation of N-methyl-d-aspartate receptors, activation of Toll-like receptor 4, disturbance in Ca handling, increased activity of nicotinamide adenine dinucleotide phosphate-oxidase and subsequent increase of production of reactive oxygen species, increased activity of nitric oxide synthase and nitric oxide synthase uncoupling and consequent impairment in nitric oxide and reactive oxygen species synthesis. Increased production of reactive species during hyperhomocysteinemia is related with increased expression of several proinflammatory cytokines, including IL-1β, IL-6, TNF-α, MCP-1, and intracellular adhesion molecule-1. All these mechanisms contribute to the emergence of diseases like atherosclerosis and related complications such as myocardial infarction, stroke, aortic aneurysm, as well as Alzheimer disease and epilepsy. This review provides evidence that supports the causal role for hyperhomocysteinemia in the development of cardiovascular disease and nervous system disorders.

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“… 95 In addition, an elevated Hcy was linked to osteoporosis, chronic renal failure, hypothyroidism, insulin resistant diabetes, polycystic ovarian syndrome, and gastrointestinal disorders. 96 - 100 Although the molecular mechanism in this role has not been fully defined, age related disorders such as acoustic dysfunction, and age related macular degeneration has been reported. 101 - 104 …”

Section: Conditions Associated With Hyperhomocysteinementioning

confidence: 99%

Hyperhomocysteinemia: Clinical Insights

Mutairi

2020

J Cent Nerv Syst Dis

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Homocysteine (Hcy) is a sulfhydryl-containing amino acid, and intermediate metabolite formed in metabolising methionine (Met) to cysteine (Cys); defective Met metabolism can increase Hcy. The effect of hyperhomocysteinemia (HHcy) on human health, is well described and associated with multiple clinical conditions. HHcy is considered to be an independent risk factor for common cardiovascular and central nervous disorders, where its role in folate metabolism and choline catabolism is fundamental in many metabolic pathways. HHcy induces inflammatory responses via increasing the pro-inflammatory cytokines and downregulation of anti-inflammatory cytokines which lead to Hcy-induced cell apoptosis. Conflicting evidence indicates that the development of the homocysteine-associated cerebrovascular disease may be prevented by the maintenance of normal Hcy levels. In this review, we discuss common conditions associated with HHcy and biochemical diagnostic workup that may help in reaching diagnosis at early stages. Furthermore, future systematic studies need to prove the exact pathophysiological mechanism of HHcy at the cellular level and the effect of Hcy lowering agents on disease courses.

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Hyperhomocysteinemia in Chronic Renal Failure: Alternative Therapeutic Strategies

Cited by 16 publications

References 21 publications

The metabolism and significance of homocysteine in nutrition and health

The metabolism and significance of homocysteine in nutrition and health

Homocysteine and homocysteine-related compounds: an overview of the roles in the pathology of the cardiovascular and nervous systems

Hyperhomocysteinemia: Clinical Insights

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