Citrate for long-term hemodialysis: prospective study of 1,009 consecutive high-flux treatments in 59 patients.

BACKGROUND: Regional citrate anticoagulation during hemodialysis is performed in selected patients at highly specialized units. We postulated that routine use of citrate at a long-term dialysis ward is safe and efficient. METHODS: During a 2-year period, we studied 1,009 consecutive citrate-anticoagulated high-flux hemodialysis treatments performed in 59 patients at our long-term dialysis ward. We used a simple citrate infusion protocol, calcium-free dialysate, and intravenous calcium substitution. Simple and clear algorithms allowed adjustments of the calcium substitution rate and dialysate settings by the attending nurse. Adverse events; indications for citrate anticoagulation; clotting; technical data; blood ionized calcium, sodium, and potassium levels; and acid-base homeostasis were analyzed prospectively. RESULTS: Of the treatments, 99.6% were accomplished successfully. Two adverse events were attributed to citrate use. Overall, ionized calcium levels were stable during the procedures and electrolyte and acid-base balances were well controlled. The use of central venous catheters for dialysis was associated with paradoxical behavior of ionized calcium levels (increasing blood ionized calcium levels despite decreased calcium infusion). Anticoagulation was excellent. CONCLUSION: Routine use of citrate anticoagulation in the setting of a long-term hemodialysis ward is safe and efficient. Measured ionized calcium levels should be interpreted with care if central venous catheters are used for vascular access because they could be biased by recirculation.

Effect of MTHFR 1298A-->C and MTHFR 677C-->T genotypes on total homocysteine, folate, and vitamin B(12) plasma concentrations in kdiney graft recipients.

The effect of 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C on total homocysteine (tHcy), folate and vitamin B(12) levels was investigated in 733 kidney graft recipients. The six major genotype combinations were used as grouping variables, and age, gender, BMI, serum creatinine, and creatinine clearance and ln-folate, ln-vitamin B(12), or logarithmus naturalis tHcy (ln-tHcy) were used as covariates in three ANCOVA and multiple stepwise linear regression models. Hyperhomocysteinemia was present in 49.7% of the patients. The allele frequency of MTHFR 677T and 1298C was 0.319 and 0.326. MTHFR genotype and all other variables were significant predictors of ln-tHcy (higher tHcy plasma levels for MTHFR 677TT/1298AA versus all other five genotype groups: P < 0. 05). BMI, creatinine clearance, ln-tHcy, and MTHFR genotype influenced ln-folate (lower folate levels for MTHFR 677TT/1298AA versus all other genotype groups: P < 0.05). Creatinine clearance and ln-tHcy were the only predictors of ln-vitamin B(12) levels. In a prespecified subgroup analysis (n = 496), the MTHFR genotype also influenced tHcy levels and compound heterozygous patients had significantly lower folate levels as compared with MTHFR 677CC/1298AA and 677CC/1298CC. This study shows that the MTHFR 677TT/1298AA and 677CT/1298AC genotypes are significant predictors of tHcy and folate plasma levels.

Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study.

Homocysteine is associated with atherosclerosis and enhanced cardiovascular risk. In previous studies, treatment with folic acid up to 15 mg/d failed to correct hyperhomocysteinemia in the majority of end-stage renal disease patients. A dose of 30 or 60 mg of folic acid per day was compared with 15 mg/d in an attempt to normalize hyperhomocysteinemia in 150 hemodialysis patients. In a randomized, double-blind, multicenter study, 144 patients completed the 4-wk treatment period and 121 patients completed the 6-mo follow-up. Total homocysteine plasma levels were reduced by 32.1% (15 mg/d), 29. 9% (30 mg/d), or 37.8% (60 mg/d) with no significant differences found between the three treatment groups. Baseline total homocysteine plasma concentration was an independent predictor of the response to folic acid therapy (P = 0.0001), whereas the 5, 10-methylenetetrahydrofolate reductase polymorphisms (MTHFR 677C --> T and 1298A --> C) had no influence. Nevertheless, patients with the MTHFR 677TT genotype more frequently attained normal total homocysteine plasma levels than patients with the CC or CT genotype (P = 0.025). In response to 60 mg of folic acid per day, TT genotype patients had lower folate plasma levels compared to CC or CT genotype patients (P = 0.016). After completion of the 4-wk treatment period with 30 or 60 mg of folic acid per day, there was a marked rebound of total homocysteine plasma levels at the end of the follow-up in patients with the MTHFR 677TT genotype, which even exceeded baseline values in several patients (P = 0.0001). This study clearly demonstrates that doses of 30 or 60 mg of folic acid per day are not more effective than 15 mg/d in reducing hyperhomocysteinemia in regular hemodialysis patients. Patients with the MTHFR 677TT genotype are more likely to realize normal total homocysteine plasma levels. Folic acid at 30 or 60 mg/d but not 15 mg/d results in a rebound of total homocysteine plasma concentrations when treatment is stopped.