title: Hyperhomocysteinemia and end-stage renal disease: determinants and association with cardiovascular disease in Tunisian patients.
abstract: 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 age- and 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 micromol/l), in HD patients (29.4 +/- 11.1 micromol/l), and in RT (19.3 +/- 6.3 micromol/l) patients compared to controls (11.9 +/- 4.1 micromol/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 B12 (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.
authors.affiliation: Laboratoire de Biochimie, Hôpital La Rabta, Tunis, Tunisia.
authors.forename: Hayet
authors.initials: H
authors.lastname: Fellah
authors.forename: Moncef
authors.initials: M
authors.lastname: Feki
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hsairi
authors.forename: Haifa
authors.initials: H
authors.lastname: Sanhaji
authors.forename: Neziha
authors.initials: N
authors.lastname: Kaabachi
authors.forename: Taieb
authors.initials: T
authors.lastname: Ben Abdallah
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.forename: Hedi
authors.initials: H
authors.lastname: Ben Maiz
authors.forename: Bernard
authors.initials: B
authors.lastname: Lacour
authors.forename: Abderraouf
authors.initials: A
authors.lastname: Mebazaa
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012306:Risk; D013927:Thrombosis / Q000097:blood / Q000209:etiology
chemical_list: D015415:Biomarkers; D006710:Homocysteine