Hyperhomocysteinemia and traditional cardiovascular disease risk factors in end-stage renal disease patients on dialysis: a case-control study

Bostom, Andrew G.; Shemin, Douglas; Lapane, Kate L.; Miller, Joshua W.; Sutherland, Patrice; Nadeau, Marie; Seyoum, Elias; Hartman, Wilburta J.; Prior, Ronald L.; Wilson, Peter W.F.; Selhub, Jacob

doi:10.1016/0021-9150(94)05470-4

Cited by 170 publications

(86 citation statements)

References 34 publications

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“…It should be stressed that many protein-bound uremic solutes have important pathophysiologic actions and might be subject to a similar enhancement of toxicity in the case of hypoalbuminemia. Candidate molecules are indoxyl sulfate (6,33,34 ), indole 3-acetic acid (35,36 ), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (37,38 ), phenol (39 ), advanced glycation end products (40 -42 ), leptin (43,44 ), homocysteine (45,46 ), hippuric acid (47,48 ), and p-hydroxyhippuric acid (49,50 ).…”

Section: Discussionmentioning

confidence: 99%

Toxicity of Free p-Cresol: A Prospective and Cross-Sectional Analysis

et al. 2003

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Background: Uremic syndrome is the consequence of the retention of solutes usually cleared by the healthy kidneys. p-Cresol can be considered a prototypic protein-bound uremic toxin. It is conceivable, analogous with drugs, that the non-protein-bound fraction of pcresol exerts toxicity. This aspect had never been evaluated, nor have the factors influencing the free fraction of p-cresol. Methods: In a transsectional study we evaluated the relationship between prehemodialysis free p-cresol and the ratio of free to total p-cresol (F:T) to clinical and biological factors in 44 chronic renal failure patients. The evolution of free p-cresol was assessed prospectively in 12 patients showing a change in serum albumin of at least 5 g/L over time. Hospitalization days attributable to infection and the free p-cresol concentrations were noted over a 1-year period. The impact of free p-cresol in vitro on leukocyte functional capacity was evaluated by chemiluminescence. Results: We observed a correlation between total and free p-cresol (r ‫؍‬ 0.84; P <0.001). In the multivariate analyses, free p-cresol and F:T showed a negative correlation with albumin. A shift from normal serum albumin to hypoalbumininemia in 12 patients led to an increase in free p-cresol from 5.9 ؎ 3.2 to 8.2 ؎ 4.5 mol/L (P <0.05; 0.64 ؎ 0.35 to 0.89 ؎ 0.49 mg/L). Free p-cresol (P <0.05) was higher in the patients hospitalized for infectious disease. In vitro, free p-cresol was higher in a 25 g/L than in a 50 g/L albumin solution (P <0.05). Leukocyte chemiluminescence production was more inhibited in the low albumin (high free p-cresol) solution (28% ؎ 6% vs 21% ؎ 8%; P <0.05).

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Section: Discussionmentioning

confidence: 99%

Toxicity of Free p-Cresol: A Prospective and Cross-Sectional Analysis

et al. 2003

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“…4,6,19,22 The metabolism of homocysteine is also dependent on other micronutrients, including the B-group vitamins. However, correction of hyperhomocysteinemia in uremia has not been demonstrated with vitamins B 6 , B 12 , 6 serine, 23 or betaine. 19 In a placebo-controlled trial, a combination of folic acid (15 mg/d) and vitamins B 6 and B 12 normalized plasma homocysteine in only one third of dialysis patients.…”

Section: Discussionmentioning

confidence: 99%

Does Folic Acid Decrease Plasma Homocysteine and Improve Endothelial Function in Patients With Predialysis Renal Failure?

et al. 2000

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Background-Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction. Although folic acid reduces hyperhomocysteinemia, the effect on adverse vascular events is unknown. We hypothesized that in patients with chronic renal failure, a condition associated with both hyperhomocysteinemia and atherosclerosis, treatment with folic acid would improve endothelial function. Methods and Results-In a prospective, double-blind protocol, 100 patients (mean age 62 years, 67 men) with predialysis chronic renal failure were randomized to 5 mg folic acid or placebo daily for 12 weeks. Endothelial function was assessed by measuring (1) endothelium-dependent dilation of the brachial artery, (2)

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“…30 Diabetic patients with advanced renal failure have a mediocre vascular prognosis, related in particular to macroangiopathies and increased arterial stiffness. 31 Finally, increased plasma levels of homocysteine 13,14 and ET 11,12 are a common feature in subjects with chronic renal failure. In the present study, such plasma levels did not differ in the presence or absence of native kidneys, indicating that the altered renal parenchyma did not contribute substantially to the increased plasma levels of both biochemical components.…”

Section: Discussionmentioning

confidence: 99%

“…8 However, in chronic renal failure, there are many other nonmechanical factors that may be related to the status of large arteries. In particular, increased levels of parathyroid hormone, 9,10 ET, 11,12 and homocysteine 13,14 have been widely reported. However, their connection with the alterations in both the structure and function of conduit vessels has not yet been established.…”

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confidence: 99%

Influence of Biochemical Alterations on Arterial Stiffness in Patients With End-stage Renal Disease

Blacher

Demuth

Guérin

et al. 1998

ATVB

190

115

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Abstract-The incremental elastic modulus of the common carotid and radial arteries is increased in patients with end-stage renal disease (ESRD), independently of blood pressure, wall stress, and the presence of atherosclerotic alterations. Whether biochemical factors may be involved in the arterial changes and related to renal dysfunction remain largely ignored. To assess this question, we measured aortic (carotid-femoral), upper-limb (carotid-radial), and lower-limb (femoral-tibial) pulse wave velocity (PWV) in 74 ESRD patients undergoing hemodialysis in comparison with 57 control subjects similar in age, sex ratio, and mean blood pressure. We evaluated arterial blood presure by sphygmomanometry, aortic calcifications and cardiac mass by echography, and routine biochemical parameters, total plasma homocysteine, and plasma endothelin levels by standard techniques. In the population of patients with ESRD, on the basis of multiple stepwise regression analysis, aortic PWV was positively and independently correlated with systolic blood pressure (PϽ.0001), age (PϽ.0001), prevalence of aortic calcification (Pϭ.0004), and the prevalence of diabetes mellitus (Pϭ.0043). Upper-limb PWV was influenced exclusively by mean blood pressure (PϽ.0001). Lower-limb PWV was positively and independently correlated with plasma total homocysteine (Pϭ.0004) and plasma endothelin (Pϭ.0187) only. At any vascular site, PWV was not independently correlated with tobacco consumption; plasma levels of cholesterol, triglyceride, fibrinogen, or hemoglobin; body mass index; or the presence of bilateral nephrectomy. Finally, plasma homocysteine was independently correlated with cardiac mass (Pϭ.0022). This study provides evidence that in ESRD patients, the stiffness of the arterial wall and cardiac mass are strongly influenced by biochemical factors related to the kidney alterations and are independent of age and blood pressure level. Increased plasma endothelin and homocysteine may be specifically involved in the vascular damage of lower limbs. (Arterioscler Thromb Vasc Biol. 1998;18:535-541.)

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Hyperhomocysteinemia and traditional cardiovascular disease risk factors in end-stage renal disease patients on dialysis: a case-control study

Cited by 170 publications

References 34 publications

Toxicity of Free p-Cresol: A Prospective and Cross-Sectional Analysis

Toxicity of Free p-Cresol: A Prospective and Cross-Sectional Analysis

Does Folic Acid Decrease Plasma Homocysteine and Improve Endothelial Function in Patients With Predialysis Renal Failure?

Influence of Biochemical Alterations on Arterial Stiffness in Patients With End-stage Renal Disease

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