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. CONCLUSION: 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.

Chlamydia pneumoniae, overall and cardiovascular mortality in end-stage renal disease (ESRD).

BACKGROUND: Cross-sectional and retrospective studies suggest that Chlamydia pneumoniae infection may contribute importantly to the high cardiovascular risk of patients with end-stage renal disease (ESRD). METHODS: We investigated the relationship between C. pneumoniae serology and survival and incident fatal cardiovascular events in a cohort of 227 ESRD patients (follow-up of 39 +/- 20 months). RESULTS: On univariate Cox regression analysis patients with anti-C. pneumoniae immunogloblulin A (IgA) titer > or = 1:16 had a significantly higher risk of all-cause and cardiovascular mortality when compared to patients without IgA antibodies. However, after data adjustment for age and smoking, the hazard ratio (HR) decreased substantially and became largely nonsignificant. Adjustments for traditional and nontraditional risk factors further decreased the independent association of IgA anti-C. pneumoniae and these outcomes (all-cause mortality HR, 1.08; 95% CI, 0.68 to 1.72; P = 0.74; cardiovascular mortality HR, 1.07; 95% CI, 0.60 to 1.89; P = 0.83). A similar loss of prognostic power was observed for IgG anti-C. pneumoniae so that in fully adjusted models the HRs were very close to those observed for IgA anti-C. pneumoniae (all-cause mortality HR, 1.13; 95% CI, 0.68 to 1.86, P = 0.64; cardiovascular mortality HR, 1.10; 95% CI, 0.60 to 2.00; P = 0.77). CONCLUSION: C. pneumoniae seropositivity is associated to shorter survival and incident fatal cardiovascular events in patients with ESRD but these associations are in large part attributable to the link between C. pneumoniae and well-established, traditional risk factors. It is highly unlikely that C. pneumoniae infection is a major risk factor in patients with ESRD.

Diagnostic value of troponin T for alterations in left ventricular mass and function in dialysis patients.

BACKGROUND: Cardiac troponin T (cTnT) is related to left ventricular (LV) mass in patients with end-stage renal disease (ESRD). Furthermore, cTnT reflects the severity of systolic dysfunction in patients with heart diseases. We tested the diagnostic value of cTnT for left ventricular hypertrophy (LVH) and LV systolic dysfunction in a large group of clinically stable hemodialysis patients without heart failure. RESULTS: CTnT was significantly (P < 0.001) higher in patients with LVH than in those with normal LV mass. In a multiple logistic regression model, adjusting for potential confounders (including cardiac ischemia), systolic pressure and cTnT (both P = 0.003) were the strongest correlates of LVH. Similarly, cTnT was significantly higher (P = 0.005) in patients with systolic dysfunction than in those with normal LV function and in a multiple logistic regression model cTnT ranked as the second independent correlate of this alteration after male sex. Serum cTnT had a high positive prediction value for the diagnosis of LVH (87%) but its negative prediction value was relatively low (44%). The positive predictive value of cTnT for LV dysfunction was low (25%) while its negative predictive value was high (93%). A combined analysis including systolic pressure (for the diagnosis of LVH) and sex (for the diagnosis of LV systolic dysfunction) augmented the diagnostic estimates to an important extent (95% positive prediction value for LVH and 98% negative prediction value for LV systolic dysfunction). CONCLUSIONS: CTnT has a fairly good diagnostic potential for the identification of LVH and for the exclusion of LV systolic dysfunction in patients with ESRD without heart failure. This marker may be useful for the screening of alterations in LV mass and function in clinically stable hemodialysis patients.