Relationship Between Homocysteine and Mortality in Chronic Kidney Disease (original) (raw)
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Clinical Chemistry and Laboratory Medicine, 2001
A moderate increase in plasma total homocysteine (tHcy) is considered to be an independent risk factor for cardiovascular disease (CVD) in the general population. Almost all chronic renal failure (CRF) patients have plasma concentration of tHcy that is elevated 3 to 4 times above normal. The prevalence of CVD, diabetes mellitus, malnutrition and hypoalbuminemia is high in CRF patients. Previous investigations have focused on the role of vitamin status on plasma tHcy in CRF patients, but little information exists on the influence of nutritional status and hypoalbuminemia on plasma tHcy in CRF, although a substantial fraction of tHcy (>70%) is protein-bound, mainly to albumin. Our study in patients with end-stage renal disease showed that more than 90% of the patients had elevated plasma tHcy levels, which were higher in patients with normal nutritional status than in malnourished patients. Moreover, plasma tHcy was inversely correlated with subjective global nutritional assessment (high values denote malnutrition) and positively correlated with serum albumin and protein intake. Hence, it seems likely that serum-albumin is a strong determinant of plasma tHcy in CRF patients and this may contribute to the lower tHcy levels in malnourished patients. Patients with diabetes mellitus had lower serum-albumin and plasma tHcy than non-diabetic patients, irrespective whether they were malnourished or not. Patients with CVD had lower (although still elevated) plasma tHcy levels than those without CVD. An explanation may be that the prevalence of diabetes mellitus, malnutrition and hypoalbuminema, i.e. factors that decrease tHcy, was higher in patients with CVD, which may explain why they had less elevated values. Assuming that hyperhomocysteinemia carries an independent risk of CVD, this implies that almost all CRF patients are exposed to this risk. CRF patients with CVD had a higher prevalence of malnutrition, hypoalbuminemia and diabetes mellitus, which was associated with a lower plasma Hcy level. This may explain why plasma tHcy was lower (although still abnormally high) in patients with CVD than in patients without CVD. The lower tHcy levels in CVD patients do not contradict the assumption that hyperhomocysteinemia is a risk factor for CVD since almost all patients are exposed to this risk, and other factors might be present that confound the relationship between the absolute tHcy levels and CVD. Our findings imply that nutritional status and serum albumin, as well as the presence of diabetes mellitus, should be taken into consideration when evaluating tHcy as a risk factor for CVD in CRF patients.
Clinical Chemistry and Laboratory Medicine, 2003
The study reports on plasma total homocysteine (tHcy) levels in Tunisian patients with chronic renal failure (CRF) and those treated with hemodialysis (HD) and renal transplant (RT). The aims of the study were to identify the determinants of tHcy concentration and to test the association between hyperhomocysteinemia and atherothrombotic disease in end-stage renal disease (ESRD). A total of 35 CRF patients on conservative treatment, 50 HD patients, and 30 RT recipients, and 31 ageand sex-matched healthy subjects were included. Plasma tHcy was assessed by a fluorescent-polarizing immunoassay method. Multivariate analysis was applied to identify the main determinants of tHcy concentration and to assess the relationship between hyperhomocysteinemia and cardiovascular disease. Plasma mean tHcy concentration was significantly increased (p < 0.001) in CRF patients (mean ± SD) (28.9 ± 9.8 µmol/l), in HD patients (29.4 ± 11.1 µmol/l), and in RT (19.3 ± 6.3 µmol/l) patients compared to controls (11.9 ± 4.1 µmol/l). Multivariate analysis using GLM ANOVA modeling demonstrated that tHcy was significantly higher in males (p = 0.02), and was related to age (p = 0.008), albumin (p = 0.005), vitamin B 12 (p = 0.002), folate (p = 0.00001), and creatinine clearance (p = 0.0008). However, tHcy was not associated with C-reactive protein and did not significantly differ between CRF, HD, or RT patients. The upper quartile of tHcy concentration was significantly associated with atherothrombotic cardiovascular disease (unadjusted odds ratio (OR) = 3.09; 95% CI, 1.11-8.61; p = 0.01). This association remained significant after adjusting for sex, age, hypertension, and smoking (multi-adjusted OR = 4.78; 95% CI, 1.92-11.9; p = 0.0008). The mean tHcy concentration was 2 to 3 times higher in ESRD patients than in subjects with normal renal function. This increase could be related to glomerular filtration rate reduction and functional B vitamins deficiency, but was not associated with inflammation. The upper quartile of tHcy concentrations confers 4.78-fold increased independent risk for atherothrombotic events in ESRD patients.
Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins
Kidney International, 2005
Data are limited on the determinants of homocysteine (tHcy) and its relationship with nutritional indices, and dietary protein intake, in the earlier stages of chronic kidney disease (CKD). Levels of tHcy were assayed at baseline (N= 804) and 1 year postrandomization (N= 678) in the Modification of Diet in Renal Disease (MDRD) Study [study A, glomerular filtration rate (GFR) 25 to 55 mL/min/1.73 m(2) and study B GFR 13 to 24 mL/min/1.73 m(2)]. Participants were randomly assigned to different blood pressure targets and protein diets and all subjects received a multivitamin supplement containing 1 mg of folic acid, 10 mg pyridoxal 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-phosphate (PLP) and 6 mug of vitamin B(12). Multivariable analyses were used to evaluate determinants of tHcy at baseline and 1 year. The prevalence of hyperhomocysteinemia (tHcy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;15 mumol/L) at baseline was 56% in study A and 85% in study B. Baseline tHcy was negatively correlated with measures of body fat and dietary protein intake. Folate, vitamin B(12), and GFR were the major determinants of tHcy levels. Of the patients with hyperhomocysteinemia at baseline, 49% and 24% reduced their tHcy levels at 1 year to &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =15 micromol/L in study A and study B, respectively. There was no association between dietary protein intake and odds of developing hyperhomocysteinemia at 1 year in study A (P= 0.94) or study B (P= 0.10). Hyperhomocysteinemia is partly amenable to correction by vitamin supplementation in CKD stages 3 and 4. There is insufficient evidence to suggest that low tHcy is associated with poor nutritional status in the MDRD Study cohort. B vitamins and GFR, but not dietary protein, are the major determinants of tHcy in this patient population.
Hyperhomocysteinemia, nutritional status, and cardiovascular disease in hemodialysis patients
Kidney International, 2000
tients have grossly elevated tHcy levels, but that the absolute Hyperhomocysteinemia, nutritional status, and cardiovascular level appears to be dependent on nutritional status, protein disease in hemodialysis patients. intake, and S Alb. The results also suggest that the lower tHcy Background. Hyperhomocysteinemia, cardiovascular disease levels in patients with CVD than in those without CVD may (CVD), and malnutrition are common in patients with endbe related to the higher prevalence of malnutrition and hypoalstage renal disease (ESRD). This study was designed to assess buminemia in the CVD patients. This is also in accordance possible relationships between total plasma homocysteine with our observation that the patients with lower tHcy had a (tHcy), nutritional status, and ischemic CVD. worse survival rate than those with higher tHcy, considering Methods. We performed a cross-sectional study in 117 unsethat malnutrition is a strong risk factor for mortality and that lected patients on maintenance hemodialysis (HD) treatment, CVD is the most common cause of death in ESRD patients. among whom there was a high prevalence of malnutrition (56%), as assessed by the subjective global nutritional assessment (SGNA), and a high prevalence of CVD (60%), and prospectively, we followed-up the overall mortality for four years. Hyperhomocysteinemia is considered an independent Results. The level of tHcy was elevated in 95% of the HD risk factor for atherosclerosis in the general population patients, and that of total plasma cysteine (tCys) was also [1, 2]. However, the relationship between hyperhomosignificantly elevated, while the plasma concentrations of methionine (Met), serine (Ser), and taurine (Tau) were significysteinemia and vascular events is complex and not well cantly lower than those in healthy controls. The 65 patients understood, and it is not clear why a high level of plasma who were malnourished according to the SGNA score had total homocysteine (tHcy) appears to promote atherosignificantly lower levels of serum albumin (S Alb), plasma IFG-1 sclerosis. Experimental studies suggest that homocysteine (p-IGF-1), tHcy, tCys, and Met than the 52 patients with normal may enhance lipoprotein oxidation, increases smooth nutritional status, whereas the levels of Ser, Tau, plasma folate, and vitamin B 12 were similar in the two groups. The prevalence muscle cell proliferation, induces endothelial dysfuncof malnutrition was 30% in the 47 patients without CVD and tion, induces endothelial activation of factor V, and rewas significantly higher (70%, P Ͻ 0.001) in the 70 patients duces protein C activation by arterial and venous endowith CVD, who also had lower tHcy, S Alb , plasma IGF-1, serum thelial cells [3]. creatinine (S Cr), and blood hemoglobin. The tHcy levels were The risk of premature and progressive occlusive vascupositively correlated with S Alb , Met, tCys, and S Cr. Stepwise, multiple-regression analysis showed that tCys, S Alb , and normallar disease is high in chronic uremic patients and accounts ized protein equivalent of nitrogen appearance (nPNA), an for more than 40% of the deaths in dialysis patients indicator of protein intake, were independent predictors of [4]. The mechanism is unclear, although hypertension, tHcy. The patients with tHcy Ͻ24 mol/L (median value) had disorders of lipid metabolism, glucose intolerance, smoka significantly worse four-year survival than those with a higher ing, and anemia, as well as inflammation/infection, may tHcy (Ն24 mol/L). Conclusions. Our results demonstrate that most of HD pabe relevant [4, 5]. In addition, malnutrition in uremic patients may be a predisposing factor to cardiac disease or may contribute to a poor prognosis by aggravating 1 These authors share equal responsibility for this article. pre-existing heart failure [5]. It is now well established that uremic patients have a high prevalence of hyperho
Homocysteine, traditional risk factors and impaired renal function in coronary artery disease
European Journal of Clinical Investigation, 2006
Background To establish whether the frequent finding of a moderate-intermediate increase in plasma total homocysteine (tHcy) causes coronary artery disease (CAD), the authors evaluated the number of coexisting major traditional risk factors, as well as the major tHcy determinants, in patients with the same degree of CAD but different tHcy levels.
Homocystein as a Risk Factor for Developing Complications in Chronic Renal Failure
Materia Socio Medica, 2015
Aim: Cardiovascular diseases are leading cause of death in patients with chronic renal failure. The aim of our study was to establish connection between levels of homocysteine and traditional and nontraditional risk factors for developing cardiovascular diseases in dialysis and pre dialysis patients. Methods: We included 33 pre dialysis (23 in stage three and 10 in stage four of chronic kidney disease) and 43 patients receiving hemodialysis longer than six months. Besides standard laboratory parameters, levels of homocysteine and blood pressure were measured in all patients. Glomerular filtration rate was measured in pre dialysis patients and dialysis quality parameters in dialysis patients. Results: Homocysteine levels were elevated in all patients (19±5.42mmol/l). The connection between homocysteine levels and other cardiovascular diseases risk factors was not established in pre dialysis patients. In patients treated with hemodialysis we found negative correlation between homocysteine levels and patients' age (p<0.05) and positive correlation between homocysteine levels and length of dialysis (p<0.01) as well as between homocysteine and anemia parameters (erythrocytes, hemoglobin), (p<0.01). Homocysteine and LDL (and total cholesterol) were in negative correlation (p<0.01). Conclusion: Homocysteine, as one of nontraditional cardiovascular diseases risk factors, is elevated in all patients with chronic renal failure and it's positive correlation with some other risk factors was found.
Total homocysteine is associated with nephropathy in non—insulin-dependent diabetes mellitus
Metabolism, 1999
Non-insulin-dependent diabetes mellitus (NIDDM) and hyperhomocysteinemia are both associated with premature vascular disease. We tested the hypothesis that homocysteine is associated with vascular disease and other diabetic complications in patients with NIDDM. The current investigation is a cross-sectional analysis of baseline variables for participants in the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Men and women aged 40 to 74 years with NIDDM and a mean diastolic blood pressure (BP) of 80 mm Hg or higher were eligible. We measured serum levels of total homocysteine (tHcy), cystathionine, and methylmalonic acid (MMA) and correlated these values with clinical and other laboratory measures of the complications of diabetes mellitus in 452 subjects, tHcy was higher in males than in females and correlated with the duration of hypertension and systolic BR tHcy was significantly correlated with MMA (r = .35, P < .0001) and cystathionine (r-.53, P < .0001) levels and inversely correlated with serum B12 (r =-.23, P < .0001) and folate (r =-.18, P < .0001). It was significantly correlated with serum creatinine (r = .28, P < .0001 for males and r = .39, P < .0001 for females) and inversely correlated with creatinine clearance {r =-.19, P < .005 for males and r =-.30, P < .0001 for females), tHcy was not increased in subjects with cardiovascular disease or retinopathy, but it was increased in those with neuropathy (10.3 v 9.3 i~mol/L, P < .05) and macroalbuminuria (11.0 v9.2 i~mol/L, P < .005). Of these subjects, 2.2% met the criteria for vitamin B12 deficiency and 1% met the criteria for folate deficiency. We conclude that elevations of tHcy in this population appear to be the result of a combination of vitamin deficiency and decreased renal function and do not appear to be a predictor of cardiovascular disease.
American Journal of Kidney Diseases, 2009
Cardiovascular disease (CVD) is the leading cause of death worldwide. CVD is causally related to "classical" risk factors such as elevated blood pressure, cholesterol, or glucose level and smoking. A causal role in the development of CVD is also suggested for numerous other factors, including an elevated plasma homocysteine concentration. Variation of homocysteinaemia is mainly due to genetic mutations and/or vitamin deficiency. The homocysteine concentration can be lowered with folate. Vitamin supplementation has thus been proposed in individuals with hyperhomocysteinaemia in order to reduce their CVD risk. On the other hand, population-based studies show little or no association between moderate hyperhomocysteinaemia and CVD risk. Nor has any randomised clinical trial clearly proven the efficacy of lowering the homocysteine concentration as a means of lowering the incidence of CVD. Hence at present it is inappropriate to recommend screening and treatment of hyperhomocysteinaemia in asymptomatic persons with or without other CVD risk. Until new evidence is available, clinicians should focus on better control of the "classical" risk factors for CVD.