Homocyst(e)ine and vascular access complications in haemodialysis patients: insights into a complex metabolic relationship

Sirrs, Sandra; Duncan, Lynda; Djurdjev, Ognjenka; Nussbaumer, Gary; Ganz, G; Frohlich, Jiri; Levin, Adeera

doi:10.1093/ndt/14.3.738

Cited by 46 publications

(36 citation statements)

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“…Hyperhomocysteinemia is present in the vast majority of maintenance dialysis patients according to almost all descriptive and prevalent studies (5)(6)(7)(8)(9)(10)(11)(12). In most of such studies, including our current study, Ͼ90% of maintenance dialysis patients have hyperhomocysteinemia, and the mean and median values of tHcy are between 20 and 25 mol/L.…”

Section: Discussionsupporting

confidence: 49%

“…Almost 72% of the patients were taking daily multivitamin supplementation designed specifically for patients with renal failure, which usually includes 1000 g of folic acid. These pills included nephrovite (209), nephrocaps (10), and other brands (46). Moreover, 86 patients were taking folic acid supplement, 1000 g/d, including 67 who were also taking above-mentioned multivitamins.…”

Section: Resultsmentioning

confidence: 99%

“…Although some studies reported positive correlations between increased tHcy and higher rate of mortality in dialysis patients (7)(8)(9), other studies failed to show such an association (39,40) or found paradoxically reversed correlations (10 -12). Sirrs et al (10) examined the association between tHcy and vascular access complications in 96 MHD patients and did not find any correlation between them. However, they found a significantly higher 9-mo mortality in MHD patients whose tHcy was Ͻ27 mol/L.…”

Section: Discussionmentioning

confidence: 98%

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A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

Kalantar-Zadeh

Block

Humphreys

et al. 2004

Journal of the American Society of Nephrology

153

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Abstract. An increased level of total plasma homocysteine (tHcy) is a risk factor for poor cardiovascular outcome in the general population. However, a decreased, rather than an increased, tHcy concentration may predict poor outcome in maintenance hemodialysis (MHD) patients, a phenomenon referred to as reverse epidemiology. Associations were examined between tHcy level and markers of malnutrition-inflammation complex syndrome and 12-mo prospective hospitalization and mortality in 367 MHD patients, aged 54.5 Ϯ 14.7 (mean Ϯ SD) years, who included 199 men and 55% individuals with diabetes. tHcy was 24.4 Ϯ 11.8 mol/L, and 94% of the patients had hyperhomocysteinemia (tHcy Ͼ13.5 mol/L). tHcy had weak to moderate but statistically significant bivariate and multivariate correlations with some laboratory markers of nutrition (serum albumin, prealbumin, creatinine, and urea nitrogen) but no significant correlation with serum C-reactive protein or two proinflammatory cytokines (IL-6 and TNF-␣).During 12 mo of follow-up, 191 MHD patients were hospitalized, 37 died, nine underwent renal transplantation, and 38 transferred out. Hospitalization rates were significantly higher in patients with lower tHcy levels. Mortality rate in the lowest tHcy quartile (17.4%) was significantly higher compared with other three quartiles (6.5 to 9.8%; Kaplan-Meier P ϭ 0.04). Relative risk of death for the lowest tHcy quartile, even after adjustment for case-mix and serum albumin, was 2.27 (95% confidence interval, 1.14 to 4.53; P ϭ 0.02). Hence, tHcy may be a more exclusive nutritional marker in MHD patients with no association with inflammatory measures. Despite a very high prevalence of hyperhomocysteinemia in MHD patients, lower values of tHcy are paradoxically associated with increased hospitalization and mortality. The lowest tHcy quartile confers a twofold increase in risk of death independent of hypoalbuminemia. The nutritional feature of tHcy in MHD patients may explain its reverse association with outcome.In the general population, an increased level of total plasma homocysteine (tHcy) is a risk factor for increased cardiovascular events and mortality (1-4). In maintenance hemodialysis (MHD) outpatients, however, the association between tHcy and clinical outcome is inconsistent and even paradoxical. Some studies have shown a poor outcome in MHD patients with hyperhomocysteinemia (5-9). However, a few recent studies have suggested that a decreased, not an increased, tHcy concentration is related to a higher prevalence of cardiovascular disease and poor outcome in these individuals (10 -12). This seems to be due to the empirical association between a low tHcy and protein-energy malnutrition, which is per se a known risk factor for poor clinical outcome in dialysis patients (11,13,14). This recently described paradoxical association between tHcy and clinical outcome in dialysis patients has now been referred to as a possible component of the reversal of the cardiovascular risks (15-17). It is believed that both inflammation and protei...

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Section: Discussionsupporting

confidence: 49%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

Kalantar-Zadeh

Block

Humphreys

et al. 2004

Journal of the American Society of Nephrology

153

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“…Of the eleven cohort studies only two failed to find an increased risk of vascular disease associated with elevated homocysteine levels. One of these studies, by Sirrs et al (1999) in haemodialysis patients, actually observed an inverse relationship between homocysteine levels and mortality, suggesting that lower homocysteine levels were actually associated with an increased risk of death. The follow-up period in this study, however, was very short.…”

Section: Prospective Studiesmentioning

confidence: 99%

Nutritional aspects and possible pathological mechanisms of hyperhomocysteinaemia: an independent risk factor for vascular disease

McKinley

2000

Proc. Nutr. Soc.

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Numerous case–control and prospective studies have identified elevated plasma homocysteine as a strong independent risk factor for cerebovascular, cardiovascular and peripheral vascular disease. Homocysteine is formed as a result of the breakdown of the dietary amino acid methionine. Once formed, homocysteine is either remethylated to methionine, or undergoes a trans-sulfuration reaction to form cysteine. The re-methylation of homocysteine to methionine is dependent on three B-vitamins, i.e. riboflavin, vitamin B12and folate. The second pathway of homocysteine metabolism is the trans-sulfuration pathway which requires both vitamin B6and riboflavin for its activity. Thus, up to four B-vitamins are required for intracellular homocysteine metabolism. Many studies have noted strong inverse relationships between homocysteine levels and the status of both vitamin B12and folate. However, the relationship between vitamin B6status and homocysteine is still uncertain. Similarly, numerous intervention studies have demonstrated effective lowering of homocysteine levels as a result of folate and vitamin B12supplementation, while the homocysteine-lowering ability of vitamin B6is unclear. Even though riboflavin plays a crucial role in both the trans-sulfuration and remethylation pathways of homocysteine metabolism, the relationship between riboflavin status and homocysteine levels has not been investigated. The exact mechanism that explains the vascular toxicity of elevated homocysteine levels is unknown at present, studies indicate that it is both atherogenic and thrombogenic. To date, no randomized clinical trial has demonstrated that lowering of homocysteine levels is beneficial in terms of reducing the prevalence of vascular disease. It is probable, however, that optimal B-vitamin status is important in the prevention of vascular disease.

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“…The development of VAT is characterized by neointimal hyperplasia and luminal stenosis 1) . Increasing evidence suggests that VAT is associated with an increase of systemic inflammation markers, such as C-reactive protein (CRP) 2) and homocysteine [3][4] , in chronic HD patients. Increases of inflammatory markers, such as interleukin-6, were also identified in vascular access stenotic lesions 5) .…”

Section: Introductionmentioning

confidence: 99%

Atrial Fibrillation linked to Vascular access Thrombosis in Chronic Hemodialysis Patients

Chen

Liu

et al. 2011

JAT

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Homocyst(e)ine and vascular access complications in haemodialysis patients: insights into a complex metabolic relationship

Cited by 46 publications

References 4 publications

A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

Nutritional aspects and possible pathological mechanisms of hyperhomocysteinaemia: an independent risk factor for vascular disease

Atrial Fibrillation linked to Vascular access Thrombosis in Chronic Hemodialysis Patients

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