Hyperhomocysteinemia and arteriovenous fistula thrombosis in hemodialysis patients.
BACKGROUND
To date, the relationship between vascular access (VA) failure and plasma total homocysteine level has been investigated only in mixed dialysis populations (ie, patients with a native arteriovenous [AV] fistula or arterial graft), whereas almost no data exist for hemodialysis patients with a native AV fistula.


METHODS
In this prospective cohort study, we examined the relationship between plasma total homocysteine level and the methylenetetrahydrofolate reductase (MTHFR) gene and VA-related incident morbidity in a cohort of 205 hemodialysis patients, all with a native AV fistula.


RESULTS
During follow-up, 78 patients experienced 1 or more VA thrombotic episodes. Patients with incident VA thrombosis had a significantly greater plasma total homocysteine level compared with patients without this event (P = 0.046). In Kaplan-Meier survival analysis, the hazard ratio for VA thrombosis increased in parallel with homocysteine level, such that patients in the third homocysteine level tertile had a relative risk for this outcome 1.72 times (95% CI, 1.21 to 2.24) greater than in those in the first tertile (log-rank test, 6.81; P = 0.009). In a multiple Cox regression model, plasma total homocysteine level was confirmed to be an independent predictor of AV fistula outcome. Plasma total homocysteine level was significantly greater (P < 0.001) in patients with the TT genotype of the MTHFR gene than in those with the CT or CC genotype.


CONCLUSIONS
VA thrombosis in dialysis patients is associated with hyperhomocysteinemia. Intervention studies are needed to clarify whether decreasing plasma homocysteine concentrations may prevent VA failure in hemodialysis patients.
Mallamaci
Francesca
F
Division of Nephrology, Consiglio Nazionale della Ricerche-Istituto di Bio-Medicina, Institute of Biomedicine, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.
Bonanno
Grazia
G
Seminara
Giuseppe
G
Rapisarda
Francesco
F
Fatuzzo
Pasquale
P
Candela
Vincenzo
V
Scudo
Paolo
P
Spoto
Belinda
B
Testa
Alessandra
A
Tripepi
Giovanni
G
Tech
Stat
S
Zoccali
Carmine
C
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D015331:Cohort Studies; D015897:Comorbidity; D003928:Diabetic Nephropathies / Q000150:complications / Q000628:therapy; D004198:Disease Susceptibility; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D015993:Life Tables; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D011446:Prospective Studies; D012008:Recurrence; D006435:Renal Dialysis; D012306:Risk; D019851:Thrombophilia / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D013927:Thrombosis / Q000453:epidemiology* / Q000209:etiology
D042965:Methylenetetrahydrofolate Reductase (NADPH2)