Subclinical vitamin K deficiency in hemodialysis patients.

BACKGROUND: Subclinical vitamin K deficiency increasingly is associated with extraosseous calcification in healthy adults. Nondietary determinants of vitamin K status include apolipoprotein E (apoE) genotype, which may influence vitamin K transport to peripheral tissues. METHODS: Serum phylloquinone concentrations and percentage of uncarboxyated osteocalcin (%ucOC) were measured by means of high-performance liquid chromatography and radioimmunoassay in 142 hemodialysis patients, respectively. ApoE phenotype was determined by means of isoelectric focusing of delipidated serum samples and Western blot analysis. Clinical and laboratory data were obtained by using chart review. RESULTS: Mean age was 62.6 +/- 14.8 (SD) years. Mean phylloquinone level was 0.99 +/- 1.12 nmol/L; 29% of patients had levels less than 0.4 nmol/L. There was no association between phylloquinone level and %ucOC. There were positive correlations between phylloquinone and total cholesterol (P = 0.017), triglyceride (P = 0.022), and ionized calcium levels (P = 0.019). There was a negative correlation between phylloquinone level and dialysis adequacy (P = 0.002). Mean %ucOC was 51.1% +/- 25.8%, and 93% of subjects had values greater than 20%. There were positive correlations between %ucOC and dialysis vintage (P < 0.001), phosphate level (P < 0.001), parathyroid hormone level (P < 0.001), albumin level (P = 0.035), and ionized calcium level (P = 0.046). Seventeen percent of patients were apoE4. Mean %ucOC was significantly greater in apoE4 carriers compared with all other apoE phenotypes (60.1% +/- 28.4% versus 47.8% +/- 24.4%; P = 0.035). In multiple regression analysis with phylloquinone level forced in, independent predictors of %ucOC were phosphate level, dialysis vintage, parathyroid hormone level, and apoE4. CONCLUSION: These data indicate suboptimal vitamin K status in hemodialysis patients, shown by low phylloquinone concentrations and high %ucOC in 29% and 93% of subjects, respectively. The apoE4 allele influences osteocalcin gamma-carboxylation in hemodialysis patients.

Cardioprotective medication use in hemodialysis patients.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in patients with renal failure, accounting for more than 50% of deaths in end-stage renal disease. Risk factor modification with the use of cardioprotective medications such as angiotensin-converting enzyme inhibitors (ACEIs), beta-adrenergic antagonists (beta-blockers), acetylsalicylic acid (ASA) and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been shown to reduce mortality in the general population. OBJECTIVE: To determine the extent of use of these medications in a hemodialysis population. METHODS: This was a cross-sectional study of a cohort of 185 prevalent hemodialysis patients. The inclusion criterion was dialysis dependence and there were no exclusion criteria. Data collection was by chart review. Contraindications to individual medication classes were not obtained. RESULTS: There were 185 patients enrolled, the mean age was 63.42+/-15.1 years and 126 (68.1%) were male. Sixty-six (35.7%) patients had diabetes and 89 (48.1%) patients had established coronary artery disease (CAD). Forty-six (24.9%) patients were on ACEIs or angiotensin II receptor blockers, 59 (31.9%) were on beta-blockers, 70 (37.8%) were on ASA and 84 (45.4%) were on statins. Although these medications were used in fewer than 60% of patients, those with CAD were more likely to be prescribed an ACEI or an angiotensin II receptor blocker (P=0.026), a beta-blocker (P<0.001), ASA (P<0.001) or a statin (P=0.001) than those without CAD. There were no differences in the use of these medications between diabetic and nondiabetic patients. CONCLUSIONS: Many hemodialysis patients are not prescribed cardioprotective medications. Given the high cardiovascular mortality in this high-risk population, more attention to reducing cardiovascular risk is warranted.

Prevention of catheter lumen occlusion with rT-PA versus heparin (Pre-CLOT): study protocol of a randomized trial [ISRCTN35253449].

BACKGROUND: Many patients with end-stage renal disease use a central venous catheter for hemodialysis access. A large majority of these catheters malfunction within one year of insertion, with up to two-thirds due to thrombosis. The optimal solution for locking the catheter between hemodialysis sessions, to decrease the risk of thrombosis and catheter malfunction, is unknown. The Prevention of Catheter Lumen Occlusion with rt-PA versus Heparin (PreCLOT) study will determine if use of weekly rt-PA, compared to regular heparin, as a catheter locking solution, will decrease the risk of catheter malfunction. METHODS/DESIGN: The study population will consist of patients requiring chronic hemodialysis thrice weekly who are dialyzed with a newly inserted permanent dual-lumen central venous catheter. Patients randomized to the treatment arm will receive rt-PA 1 mg per lumen once per week, with heparin 5,000 units per ml as a catheter locking solution for the remaining two sessions. Patients randomized to the control arm will receive heparin 5,000 units per ml as a catheter locking solution after each dialysis session. The study treatment period will be six months, with 340 patients to be recruited from 14 sites across Canada. The primary outcome will be catheter malfunction, based on mean blood flow parameters while on hemodialysis, with a secondary outcome of catheter-related bacteremia. A cost-effectiveness analysis will be undertaken to assess the cost of maintaining a catheter using rt-PA as a locking solution, compared to the use of heparin. DISCUSSION: Results from this study will determine if use of weekly rt-PA, compared to heparin, will decrease catheter malfunction, as well as assess the cost-effectiveness of these locking solutions.

Thrombophilia and the risk for hemodialysis vascular access thrombosis.

Vascular access thrombosis is the most common and costly complication in hemodialysis patients. The role of thrombophilia in access thrombosis is not established. A case-control study was conducted of 419 hemodialysis patients to determine whether thrombophilia was associated with arteriovenous fistula or graft thrombosis. Participants were enrolled from three in-center and five satellite dialysis units associated with a Canadian academic health science center that provides dialysis services in a catchment area of one million. Patients were tested for factor V Leiden, prothrombin gene mutation, factor XIII genotype, methylenetetrahydrofolate reductase genotype, lupus anticoagulant, anticardiolipin antibody, factor VIII, homocysteine, and lipoprotein (a) concentrations. Overall, 59 (55%) patients with access thrombosis had at least one thrombophilia compared with 122 (39%) patients without access thrombosis (unadjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.23 to 2.98). After controlling for important risk factors, the association between any thrombophilia and access thrombosis remained (adjusted OR, 2.42; 95% CI, 1.47 to 3.99). For each additional thrombophilic disorder, the odds of access thrombosis increased significantly (adjusted OR, 1.87; 95% CI, 1.34 to 2.61). This study suggests that thrombophilia is associated with access thrombosis in dialysis patients. Large, multicenter, prospective cohort studies are needed to confirm the observations from this case-control study.

Pre-dialysis clinic attendance improves quality of life among hemodialysis patients.

BACKGROUND: Although previous research has demonstrated that referral to pre-dialysis clinics is associated with favourable objective outcomes, the benefit of a pre-dialysis clinic from the perspective of patient-perceived subjective outcomes, such as quality of life (QOL), is less well defined. METHODS: A retrospective incident cohort study was conducted to determine if pre-dialysis clinic attendance was a predictor of better QOL scores measured within the first six months of hemodialysis (HD) initiation. Inclusion criteria were HD initiation from January 1 1998 to January 1 2000, diagnosis of chronic renal failure, and completion of the QOL questionnaire within six months of HD initiation. Patients receiving HD for less than four weeks were excluded. An incident cohort of 120 dialysis patients was identified, including 74 patients who attended at least one pre-dialysis clinic and 46 patients who did not. QOL was measured using the SF 36-Item Health Survey. Independent variables included age, sex, diabetes, pre-dialysis clinic attendance and length of attendance, history of ischemic heart disease, stroke, peripheral vascular disease, heart failure, malignancy, and chronic lung disease, residual creatinine clearance at dialysis initiation, and kt/v, albumin and hemoglobin at the time of QOL assessment. Bivariate and multivariate linear regression analyses were used to identify predictors of QOL scores. RESULTS: Multivariate analysis suggested that pre-dialysis clinic attendance was an independent predictor of higher QOL scores in four of eight health domains (physical function, p < 0.01; emotional role limitation, p = 0.01; social function, p = 0.01; and general health, p = 0.03), even after statistical adjustment for age, sex, residual renal function, kt/v, albumin, and co-morbid disease. Pre-dialysis clinic attendance was also an independent predictor of the physical component summary score (p = 0.03). CONCLUSIONS: We conclude that pre-dialysis clinic attendance favourably influences patient-perceived quality of life within six months of dialysis initiation.