Prevalence and determinants of hyperhomocysteinemia in hemodialysis and peritoneal dialysis

Moustapha, Ali; Gupta, Anjan; Robinson, Killian; Arheart, Kristopher L.; Jacobsen, Donald W.; Schreiber, Martin J.; Dennis, Vincent W.

doi:10.1046/j.1523-1755.1999.00378.x

Cited by 98 publications

(74 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10 Similarly, many studies have reported that hHcys still occurs in ESRD patients receiving hemodialysis therapy. 3,9,11 In some patients with hypertension, in addition, a long-term diuretic therapy resulted in hHcys, but their GFR or renal functions were normal. 5,15 All these data indicate that elevated plasma tHcys levels in the patients with ESRD or hypertension may not depend on a decrease in GFR.…”

Section: Discussionmentioning

confidence: 99%

Implications of Hyperhomocysteinemia in Glomerular Sclerosis in Hypertension

Chen

Zou

2002

Hypertension

View full text Add to dashboard Cite

Abstract-Hyperhomocysteinemia (hHcys) has been recognized as a new risk factor for cardiovascular diseases independent of plasma lipid levels or other factors. However, it remains unknown whether hHcys is implicated in the target organ damages associated with hypertension. The present study first examined the possible role of hHcys in the development of glomerulosclerosis in Dahl salt-sensitive (DS) hypertensive rats. High-performance liquid chromatography showed that plasma total homocysteine (tHcys) concentration was 7.64Ϯ0.29 mol/L in conscious DS rats on a low salt (0.4% NaCl) diet, which was higher than 5.23Ϯ0.25 mol/L in Dahl salt-resistant normotensive rats. When these rats were exposed to a high salt (4% NaCl) diet, plasma tHcys markedly increased in DS rats (14.7Ϯ1.31 mol/L) but not in Dahl salt-resistant rats (5.34Ϯ0.54 mol/L). An iron chelater, desferrioxamine (0.3 mg/kg IV per day), completely normalized high salt-induced elevations of plasma tHcys and significantly attenuated the sclerotic changes in the glomeruli in DS rats. To further determine whether hHcys has an independent effect in the development of glomerulosclerosis, Sprague-Dawley rats were fed drinking water containing methionine (1 g/kg per day) for 6 weeks to produce hHcys. In these rats, plasma tHcys increased to 12.5Ϯ1.9 mol/L (versus 6.1Ϯ2.6 mol/L in control rats), and the aorta exhibited typical sclerotic changes, but arterial pressure was not altered. Urinary protein excretion increased to 52Ϯ2 mg/24 hours (versus 17Ϯ2 mg/24 hours in control rats), and the glomerular mesangium was expanded with glomerular hypercellularity, capillary collapse, and fibrous deposition in the rats with hHcys. These results suggest that elevated plasma homocysteine may be an important pathogenic factor for glomerular damage in hypertension independent of arterial pressure.

show abstract

Section: Discussionmentioning

confidence: 99%

Implications of Hyperhomocysteinemia in Glomerular Sclerosis in Hypertension

Chen

Zou

2002

Hypertension

View full text Add to dashboard Cite

show abstract

“…Födinger et al [22]have reported that MTHFR VV genotype, serum albumin, and plasma folate influence the plasma homocysteine level, but that gender, plasma vitamin B 12 , and serum creatinine do not. Several studies [28, 29, 30]have shown that the plasma homocysteine concentration shows significant negative correlations with plasma vitamin B 12 and plasma folate concentrations in patients on hemodialysis. However, the exact mechanism of hyperhomocysteinemia in hemodialysis patients remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Methylenetetrahydrofolate Reductase Gene Polymorphism, Hyperhomocysteinemia, and Cardiovascular Diseases in Chronic Hemodialysis Patients

Morimoto

Haneda

Okamoto

et al. 2001

Nephron

View full text Add to dashboard Cite

Cardiovascular disease (CVD) is the principle cause of death in patients with end-stage renal disease. Some gene polymorphisms and hyperhomocysteinemia have been implicated in the pathogenesis of CVD. The aim of this study was to assess the relationships between angiotensin-converting enzyme genotype, endothelial nitric oxide synthase genotype, and methylenetetrahydrofolate reductase (MTHFR) genotype and CVD in patients on hemodialysis and to clarify the determinants of plasma homocysteine level. One hundred and sixty-eight patients on hemodialysis (87 males and 81 females, mean age 60.7 ± 13.1 years) were included. A history of CVD was present in 25% of the patients. There was a significant difference in the distributions of MTHFR non-VV genotype and MTHFR VV genotype between patients with a CVD history and patients without a CVD history, but no difference in the distributions of angiotensin-converting enzyme genotypes and endothelial nitric oxide synthase genotypes. The plasma homocysteine concentration was significantly higher in patients with MTHFR VV genotype than in patients with MTHFR non-VV genotype. The plasma homocysteine concentration was negatively correlated with plasma vitamin B₁₂ concentration and plasma folate concentration. On stepwise multiple-regression analysis for the predictors of plasma homocysteine concentration, MTHFR VV genotype and gender were significant. In conclusion, MTHFR polymorphism may be a risk factor for CVD in patients on hemodialysis, and MTHFR VV genotype and gender may be strong determinants of the plasma homocysteine level.

show abstract

“…Many studies indeed demonstrated that clinically stable renal transplant recipients have an excess prevalence of hHcys, suggesting that improvement of the GFR in these patients does not completely restore plasma Hcys to normal [9, 29]. Similarly, in ESRD patients receiving hemodialysis therapy, improvement of the renal function could not restore plasma Hcys concentrations to normal levels [35, 36]. In some patients with hypertension, moreover, long-term diuretic therapy results in hHcys, but their GFR or renal functions are normal [3].…”

Section: Hhcys and Esrdmentioning

confidence: 99%

Mechanisms of Homocysteine-Induced Glomerular Injury and Sclerosis

Li²

2007

Am J Nephrol

View full text Add to dashboard Cite

Hyperhomocysteinemia (hHcys) has been recognized as a critical risk or pathogenic factor in the progression of end-stage renal disease (ESRD) and in the development of cardiovascular complications related to ESRD. Recently, evidence is accumulating that hHcys may directly act on glomerular cells to induce glomerular dysfunction and consequent glomerular sclerosis, leading to ESRD. In this review, we summarize recent findings that reveal the contribution of homocysteine as a pathogenic factor to the development of glomerular sclerosis or ESRD. In addition, we discuss several important mechanisms mediating the pathogenic action of homocysteine in the glomeruli or in the kidney, such as lo- cal oxidative stress, endoplasmic reticulum stress, homocysteinylation, and hypomethylation. Understanding these mechanisms may help design new approaches to develop therapeutic strategies for treatment of hHcys-associated end-organ damage and for prevention of deterioration of kidney function and ultimate ESRD in patients with hypertension and diabetes mellitus or even in aged people with hHcys.

show abstract

Prevalence and determinants of hyperhomocysteinemia in hemodialysis and peritoneal dialysis

Abstract: Hyperhomocysteinemia is more prevalent and intense in HD patients compared with those on PD. The homocysteine response may become refractory to excess folate supplementation in PD patients.

Cited by 98 publications

References 23 publications

Implications of Hyperhomocysteinemia in Glomerular Sclerosis in Hypertension

Implications of Hyperhomocysteinemia in Glomerular Sclerosis in Hypertension

Methylenetetrahydrofolate Reductase Gene Polymorphism, Hyperhomocysteinemia, and Cardiovascular Diseases in Chronic Hemodialysis Patients

Mechanisms of Homocysteine-Induced Glomerular Injury and Sclerosis

Contact Info

Product

Resources

About