Randomized trial of high-flux vs low-flux haemodialysis: effects on homocysteine and lipids.

BACKGROUND: Uncontrolled studies have found that high-flux haemodialysis favourably modifies homocysteine and lipid profiles. We sought to confirm these findings by carrying out a randomized prospective comparison of high-flux and low-flux polysulphone in chronic, stable dialysis patients. METHODS: Forty-eight patients were randomly assigned to either high or low-flux dialysis for 3 months. Serum levels of homocysteine, lipoprotein (a), and lipids were compared between the treatment groups at monthly intervals. RESULTS: All patient characteristics and laboratory variables were equally distributed between the groups at baseline. Over the study duration, we observed no differences between high- and low-flux treatment groups for the following outcomes: pre-dialysis homocysteine, lipoprotein (a), total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides (all P>0.05). Geometric mean (interquartile range) homocysteine at baseline was 20.0 (16.8-24.5) and 19.5 (15.3-22.0) micromol/l for the high-and low-flux groups respectively (P=0.80), and levels did not change significantly during the study. We did demonstrate a more pronounced intradialytic effect of high-flux dialysis on homocysteine levels, which fell during dialysis by 42%, compared to 32% with low-flux dialysis (P<0. 001). CONCLUSIONS: In this randomized controlled trial, the effects of high-flux and low-flux haemodialysis on homocysteine and lipid profiles were comparable. The greater intradialytic effect of high-flux dialysis on homocysteine did not translate into a significant difference in pre-dialysis levels after 3 months of study.     

The effect of vitamin B6 and folate supplements on plasma homocysteine and serum lipids levels in patients on regular hemodialysis

Background: Hyperhomocysteinemia is anindependent risk factor for cardiovascularevents. The aim of this study was to show theresults of the reduction of homocysteine in endstage renal failure patients on hemodialysis,as it is known, have higher levels ofhomocysteine than other groups of subjects.Methods: Plasma homocysteineconcentration was determined before and afterthe administration of vitamin B₆ and folicacid in 12 patients (males : 6) on regulardialysis therapy. Mean monthly fasting serumconcentrations of total cholesterol (TCHOL),HDL-chol, LDL-chol and triglycerides (TRG) weredetermined for a period 68 months (12–120months) before and 26 months after theadministration of vitamin B₆ and folicacid. Results: Mean serum concentrations forfolic acid and vitamin B₁₂ before andafter the administration were: folic acid:5.03 ± 4.9 and 18.0 ± 19.2 ng/ml,(p < 0.0001) and B₁₂ : 456 ± 257 and514.38 ± 307 pg/mL respectively). Plasmahomocysteine was reduced significantly afterthe administration of above drugs (from47 ± 14 to 29 ± 9 µmol/mL, p < 0.001).This reduction of homocysteine resulted in amodification of the patients' lipidemicprofile: Serum LDL-chol was decreasedsignificantly (119 ± 38 mg/dL to110 ± 35 mg/dL, p<0.005). TCHOL and TRG werealso decreased but not significantly(190 ± 45 mg/dL to 187 ± 43 mg/dL and116 ± 63 mg/dL to 108 ± 47 mg/dLrespectively)). Serum concentrations HDL-cholwere increased significantly (from42 ± 10 mg/dL to 47 ± 10 mg/dL, p < 0.001).The atherogenic index for cholesterol, LDL/HDL,was 1.6 times lower after the drugs receiving(before: LDL/HDL = 3.1 and after: LDL/HDL = 2.5,p < 0.001).Conclusions: These results indicate thatthe folate and vitamin B₆ supplementationresulted in reduction of homocysteine levelsand improvement of lipidemic profile in regulardialysis patients.     

Effect of glutamate carboxypeptidase II and reduced folate carrier polymorphisms on folate and total homocysteine concentrations in dialysis patients

This study was designed to examine the effect of two single nucleotide polymorphisms in the reduced folate carrier 1 (RFC1 80G>A) and the glutamate carboxypeptidase 2 (GCP2 1561C>T) gene on total homocysteine (tHcy) plasma level and folate status in 120 chronic dialysis patients. Red blood cell folate concentration was higher in patients with the GCP2 CT or TT genotype (ANOVA, P = 0.04). Among patient groups with different RFC1 genotypes, red blood cell folate level was not significantly different. A multivariate analysis confirmed that the GCP2 1561C>T genotype (P = 0.011) had a significant influence on the red blood cell folate concentration. Overall, serum folate, creatinine, and the GCP2 polymorphism explained nearly 50% of the variance of red blood cell folate. A linear multivariate regression analysis showed that red blood cell folate (P < 0.001), creatinine (P < 0.001), and the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677T allele (P = 0.013) are independent predictors of tHcy plasma level explaining 49% of the variance of tHcy plasma concentration. GCP2 1561C>T and RFC1 80G>A showed no effect on tHcy and folate plasma level. In conclusion, GCP2 1561C>T, but not RFC1 80G>A, is a predictor of red blood cell folate level in chronic dialysis patients. Both polymorphisms have no major effect on tHcy plasma concentration in end-stage renal disease patients.     

Is folate supplementation necessary in hemodialysis patients on erythropoietin therapy.

The need for folate supplementation in hemodialysis (HD) patients receiving erythropoietin (EPO) therapy remains unknown. Twenty stable HD patients, taking folic acid, 5 mg, after a meal during each HD session were divided into two groups. Supplementation was withdrawn at the start of the study in group 1 and after a 12-month-observation period in group 2. EPO treatment, 1500 u x 3/week i.v. was started in both groups. Pre- and post-HD blood samples were obtained at the beginning of the study for baseline values, then 12 and 18 months later. Folate levels decreased to normal after withdrawal of the supplements. The response to EPO treatment was exactly the same in both groups and the anemia was effectively improved. We conclude that there is no need for routine folic acid supplements in HD patients receiving EPO therapy if they are eating an adequate mixed diet.     

Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations in haemodialysis patients receiving high-dose folic acid supplementation.

BACKGROUND: Hyperhomocysteinaemia, which is considered to be induced by impairment of the remethylation pathway in patients with chronic renal failure (CRF), cannot be cured solely by folic acid therapy. In the present study, we investigated the additional benefit of administration of methylcobalamin, which is a co-enzyme in the remethylation pathway, on lowering total homocysteine (tHcy) plasma concentrations in haemodialysis (HD) patients receiving high-dose folic acid supplementation. METHODS: In order to assess the efficacy on lowering plasma tHcy levels (fasting concentration), 21 HD patients, were randomly assigned and provided folic acid supplementation: 15 mg/day orally (group I, n=7); methylcobalamin 500 mg intravenously after each HD, in addition to folic acid (group II, n=7); or vitamin B(6) (B(6)), 60 mg/day orally, in addition to folic acid and methylcobalamin (group III, n=7). All patients were treated for 3 weeks. A methionine-loading test was conducted before and after supplementation. The following measurements were also made before and after supplementation for each group: serum folic acid, B(6), and vitamin B(12) (B(12)) concentrations (including measurement of proportion of methylcobalamin fraction). Twelve HD patients receiving methylcobalamin alone served as the HD control group and seven healthy volunteers served as the normal control group for this study. RESULTS: In our randomized HD patients the proportions of methylcobalamin fraction (48.3+/-7.5%) and plasma vitamin B(6) concentration (2.9+/-1.1 ng/ml) were significantly lower than in the normal controls (methylcobalamin 58.7+/-2.2%, P<0.01; B(6) 20.1+/-10.8 ng/ml, P<0.01), while folic acid and vitamin B(12) were not significantly different from the normal controls. Mean percentage reduction in fasting tHcy was 17.3+/-8.4% in group I, 57.4+/-13.3% in group II, 59.9+/-5.6% in group III, and 18.7+/-7.5% in HD controls. The power of the test to detect a reduction of tHcy level was 99.6% in group II and 99.9% in group III when type I error level was set at 0.05. Groups II and III had normal results for the methionine-loading test after treatment. Treatment resulted in normalization of fasting tHcy levels (<12 ng/ml) in all 14 patients treated by the combined administration of methylcobalamin and supplementation of folic acid regardless of whether there was supplementation of vitamin B(6). CONCLUSION: The benefit of methylcobalamin administration on lowering plasma tHcy levels in HD patients was remarkable. Our study suggested that both supplementations of high-dose folic acid and methylcobalamin are required for the remethylation pathway to regain its normal activity. This method could be a therapeutic strategy to combat the risk associated with atherosclerosis and cardiovascular disease in patients with chronic renal failure.     

A controlled trial of the effect of folate supplements on homocysteine, lipids and hemorheology in end-stage renal disease

Elevated plasma homocysteine (Hcy), dyslipidemia and hemorheological abnormalities all occur commonly in end-stage renal disease (ESRD) and are recognized risk factors for arteriosclerosis. To study the effect of folate supplementation on these factors we conducted a randomized controlled trial. Thirteen hemodialysis (HD) and 8 continuous ambulatory peritoneal dialysis (CAPD) patients received either 5 mg folic acid daily or placebo for 3 months. After 1 and 3 months, fasting blood samples were taken for Hcy, lipid profile, blood and plasma viscosity, red blood cell (RBC) osmotic fragility, plasma fibrinogen concentration and in vivo platelet aggregability. At baseline, the CAPD patients had a higher mean plasma fibrinogen concentration than the HD patients and they also tended to have higher mean plasma viscosity. Folate-treated patients showed marked increases in RBC folate and an average decrease in plasma Hcy concentration of 33%. Mean total cholesterol, LDL cholesterol and triglyceride concentrations decreased significantly in the CAPD patients who took folate. Folate had no significant effect on hemorheology. In conclusion, folate supplements in ESRD reduce plasma Hcy concentrations and may improve lipid profiles. In our patients, hemorheological abnormalities were more marked in patients on CAPD than in those on HD and were not improved by folate supplementation.     

Randomized, clinical trial comparison of trisodium citrate 30% and heparin as catheter-locking solution in hemodialysis patients

Interdialytic hemodialysis catheter-locking solutions could contribute to a reduction of catheter-related complications, especially infections. However, they can cause side effects because of leakage from the tip of the catheter. Recently, trisodium citrate (TSC) has been advocated because of its antimicrobial properties and local anticoagulation. In a multicenter, double-blind, randomized, controlled trial, TSC 30% was compared with unfractionated heparin 5000 U/ml for prevention of catheter-related infections, thrombosis, and bleeding complications. The study was stopped prematurely because of a difference in catheter-related bacteremia (CRB; P < 0.01). Of 363 eligible patients, 291 could be randomized. The study included 98 tunneled cuffed catheters and 193 untunneled. There were no significant differences in patient and catheter characteristics on inclusion. In the heparin group, 46% of catheters had to be removed because of any complication compared with 28% in the TSC group (P = 0.005). CRB rates were 1.1 per 1000 catheter-days for TSC versus 4.1 in the heparin group (P < 0.001). For tunneled cuffed catheters, the risk reduction for CRB was 87% (P < 0.001) and for untunneled catheters was 64% (P = 0.05). Fewer patients died from CRB in the TSC group (0 versus 5; P = 0.028). There were no differences in catheter flow problems and thrombosis (P = 0.75). No serious adverse events were encountered. Major bleeding episodes were significantly lower in the TSC group (P = 0.010). TSC 30% improves overall patency rates and reduces catheter-related infections and major bleeding episodes for both tunneled and untunneled hemodialysis catheters. Flow problems are not reduced.     

Controlled trial of calcitriol in hemodialysis patients

We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation.     

Randomized controlled trial of prophylactic repair of hemodialysis arteriovenous graft stenosis

BACKGROUND: Previous nonrandomized studies suggest that prophylactic repair of hemodialyisis arteriovenous (AV) graft stenosis reduces thrombosis rates and increases cumulative graft survival. The present study is a randomized trial comparing prophylactic repair of AV graft stenosis with repair at the time of thrombosis. METHODS: Sixty-four patients with elevated static venous pressure measured in an upper extremity AV graft were randomized to Intervention or Observation. Monthly static venous pressure/systolic blood pressure ratios (SVPR) were determined for all patients throughout the duration of study participation. Patients in the Intervention group underwent angiography and repair of identified stenoses if the monthly SVPR was elevated (>/=0.4). Patients in the Observation group underwent stenosis repair only in the event of access thrombosis or clinical evidence of access dysfunction. The primary end point was access abandonment. RESULTS: Access abandonment occurred in 14 patients in the Intervention group and 14 patients in the Observation group during the 3.5-year study period. Time to access abandonment did not differ significantly between the treatment groups (hazard ratio for randomization to Intervention 1.75, 95% CI 0.80-3.82, P= 0.16). The proportion of patients with a thrombotic event was greater in the Observation group (72%) than in the Intervention group (44%) (P= 0.04), but overall thrombosis rates were similar in the groups. CONCLUSION: Compared with a strategy of observation and repair of accesses only in the event of thrombosis, prospective static venous pressure monitoring with prophylactic stenosis repair did not prolong graft survival.     

Randomized trial of bioelectrical impedance analysis versus clinical criteria for guiding ultrafiltration in hemodialysis patients: effects on blood pressure, hydration status, and arterial stiffness

Background

Chronic fluid overload is common in maintenance hemodialysis (HD) patients and is associated with severe cardiovascular complications, such as arterial hypertension, left ventricular hypertrophy, congestive heart failure, and arrhythmia. Therefore, a crucial target of HD is to achieve the so-called dry weight; however, the best way to assess fluid status and dry weight is still unclear. Dry weight is currently determined in most dialysis units on a clinical basis, and it is commonly defined as the lowest body weight a patient can tolerate without developing intra-dialytic or inter-dialytic hypotension or other symptoms of dehydration. One of the most promising methods that have emerged in recent years is bioelectrical impedance analysis (BIA), which estimates body composition, including hydration status, by measuring the body??s resistance and reactance to electrical current. Our objective was to study the effect BIA-guided versus clinical-guided ultrafiltration on various cardiovascular disease risk factors and markers in HD patients.

Materials and methods

We included 135 HD patients from a single center in a prospective study, aiming to compare the long-term (12?months) effect of BIA-based versus clinical-based assessment of dry weight on blood pressure (BP), pulse wave velocity (PWV), and serum N-terminal fragment of B-type natriuretic peptide (NT-proBNP). The body composition was measured using the portable whole-body multifrequency BIA device, Body Composition Monitor??BCM^? (Fresenius Medical Care, Bad Homburg, Germany).

Results

In the ??clinical?? group there were no changes in BP, body mass index (BMI), and body fluids. The PWV increased from 7.9?±?2.5 to 9.2?±?3.6?m/s (P?=?0.002), whereas serum NT-proBNP decreased from 5,238 to 3,883?pg/ml (P?=?0.05). In the ??BIA?? group, BMI and body volumes also did not change; however, there was a significant decrease in both systolic BP, from 144.6?±?14.7 to 135.3?±?17.8?mmHg (P?P?P?=?0.001) and NT-proBNP decreased from 7,552 to 4,561?pg/ml (P?=?0.001).

Conclusion

BIA is not inferior and possibly even better than clinical criteria for assessing dry weight and guiding ultrafiltration in HD patients.     

Multicenter trial of L-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects

Since carnitine deficiency has been reported in some patients undergoing maintenance hemodialysis, we studied the effects of intravenous infusion of L-carnitine or placebo at the end of each dialysis treatment. The trial, which lasted seven months (one month baseline, 6 months treatment) was multicenter, double blind, placebo controlled, and randomized. Eighty-two long-term hemodialysis patients, who were given either carnitine (N = 38) or placebo (N = 44), completed this study. In each group, clinical and biochemical parameters during treatment were compared with baseline values. Intra-dialytic hypotension and muscle cramps were reduced only in the carnitine treated group, while improvement in post-dialysis asthenia was noticed in both carnitine and placebo groups. Maximal oxygen consumption, measured during a progressive work exercise test, improved significantly in the carnitine group (111 +/- 50 ml/min. P less than 0.03) and was unchanged in the placebo group. L-carnitine treatment was associated with a significant drop in pre-dialysis concentrations of serum urea nitrogen, creatinine and phosphorus (means +/- SEM, 101 +/- 4.5 to 84 +/- 3.9, 16.7 +/- 0.67 to 14.7 +/- 0.64, and 6.4 +/- 0.3 to 5.5 +/- 0.4 mg/dl, respectively, P less than 0.004). No significant changes in any of these variables were noticed in the placebo group. Mid-arm circumference and triceps skinfold thickness were measured in 11 carnitine and 13 placebo treated patients. Calculated mid-arm muscle area increased in the carnitine patients (41.37 +/- 2.68 to 45.6 +/- 2.82 cm2, P = 0.05) and remained unchanged in the placebo patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationships between homocysteine and related amino acids in chronic hemodialysis patients.

AIMS: Homocysteine (Hcy) has emerged as an important risk factor for atherosclerotic disease. Elevated levels in chronic dialysis patients may contribute to high vascular mortality, but little is known about levels of related amino acids in this group. In an observational study in the clinical setting we sought to document these. METHODS: In 114 hemodialysis patients pre-dialysis total plasma homocysteine, vitamin B12 and red blood cell (RBC) folate concentrations were measured. In a subgroup of patients (n = 42), other plasma amino acids were measured pre- and post-dialysis. All patients were routinely taking oral folic acid supplements (1.2 mg per week). RESULTS: Elevated homocysteine concentrations were found in all patients (geometric mean 33.1 umol/l, range 13.8 - 69.2 umol/l, laboratory reference range (RR) 3-13 umol/l). RBC folate levels were high (1223 +/- 54.5 nmol/l mean +/- SE, RR 300 - 710 nmol/l) and inversely related to pre-dialysis plasma Hcy (r = -0.44, p < 0.001). Hcy levels were not related to vitamin B12 levels. A history of vascular disease was not associated with higher concentrations of Hcy. Hcy clearance on dialysis was substantial (mean Hcy reduction 33 +/- 14%). While plasma methionine levels were normal, serine levels were significantly lower than the reference range (59.3 +/- 2.39 umol/l (mean +/- SE, RR 70 - 195 umol/l)) and directly related to levels of glycine (r = 0.52, p < 0.001). Glycine levels were within normal range. Although overall levels were low, higher serine levels were related to elevated homocysteine (r = 0.42, p < 0.01). Dialytic loss of glycine, serine and methionine was moderate. CONCLUSION: An inverse association between RBC folate and homocysteine levels extended to 3 times the upper limit of normal for folate, suggesting a role for high dose folic acid supplementation in the treatment of renal-failure related hyperhomocysteinemia. Low serine levels are expected as it is primarily synthesized in the kidney. The direct relationship between serine and homocysteine is consistent with the reported lack of effect of serine supplements on high Hcy levels.     

Folate supplementation in peritoneal dialysis patients with normal erythrocyte folate: effect on plasma homocysteine

The possible role of folate supplementation in reducing hyperhomocysteinemia in dialysis patients has been reported in several recent papers. However, scant data are available for peritoneal dialysis patients; besides, none of these studies investigated either the role of intraerythrocyte folate concentration or the presence of side effects caused by folate administration. Sixty-six peritoneal dialysis patients with hyperhomocysteinemia (>15 micromol/l) and normal folate status (as assessed by erythrocyte folate level >600 nmol/l) were randomly allocated to receive either oral folate (5 mg/day) or no vitamin supplementation. After 2 months of therapy, patients were requested to answer a questionnaire investigating the occurrence of symptoms possibly related to folate supplementation. Twenty-nine treated patients and 30 untreated controls completed the study. In the treated patients, serum and erythrocyte folate increased significantly (p < 0.0001) (respectively from 10.6 +/- 4.9 to 237 +/- 231 nmol/l and from 1,201 +/- 297 to 2,881 +/- 294 nmol/l) to levels at the uppermost limit of detection by laboratory methods. Serum vitamin B(12) levels did not change. Plasma homocysteine levels decreased from 54 +/- 32 to 23 +/- 14 micromol/l after folate supplementation and remained unchanged in the control group. After 4 months of folate therapy, homocysteine concentration was within the normal range in 5 patients (17%) and below 30 micromol/l in the other 21 (72%). Folate therapy resulted in a decrease in homocysteine of more than 50% in 45% of the patients and decrease of more than 20% in a further 38%. No significant symptoms were reported. Thus, serum and erythrocyte folate increase confirms that normal folate levels are inadequate in dialysis patients, even if serum and erythrocyte levels before folate supplementation cannot predict the effect on homocysteine plasma levels.     

左旋卡尼汀治疗维持性血液透析患者肉碱缺乏症的临床研究

目的研究静脉注射左旋卡尼汀对维持血液透析（ＨＤ）患者肉碱缺乏症的治疗作用。方法采用多中心、双盲、随机、对照的研究方法,选择ＨＤ患者１９７例,分为治疗组、对照组和开放组,每次透析结束后,治疗组和开放组静脉注射左旋卡尼汀１ｇ,对照组注射生理盐水,为期３个月。结果治疗组和开放组体力、精神状态、食欲、恶心、呕吐、透析耐受性、透析中肌痉挛或低血压等症状的改善十分显著,血浆肉碱浓度明显升高（治疗前比治疗后：２８８２±１２５８ｖｓ．１８１３１±７４５７,Ｐ＜００１）,对照组以上各项均无变化,治疗组与对照组相比变化差异十分显著（Ｐ＜００１）;治疗组及开放组血浆总蛋白、白蛋白、前白蛋白和转铁蛋白等营养参数也明显升高。左旋卡尼汀治疗主要不良反应为转氨酶轻度升高和血小板降低,发生率分别为５．３％和２．３％,停药即可恢复正常。结论左旋卡尼汀能安全有效地治疗维持ＨＤ患者肉碱缺乏症。     

Neither folic nor folinic acid normalize homocysteine levels in hemodialysis patients

AIMS: A greater decrease in total homocystein (tHcy) has been reported in patients on hemodialysis (HD) following the administration of reduced forms of folic acid (FA), however, the effect of the administration of moderated doses of oral levofolinic acid has not been compared with that of FA. We decided to perform a study to evaluate the therapeutic effectiveness of oral levofolinic acid, the pharmacologically active form of folinic acid in our population of HD patients already on treatment with oral FA and vitamin B6. MATERIAL AND METHODS: We undertook a prospective study in HD patients who had been receiving oral supplements of both FA 5 mg every 48 hours and vitamin B6 40 mg every 7 days during at least 6 months, with a 17% initial decrease of tHcy levels. Patients matched for age, sex and time on HD were assigned to 1 of 2 groups: Those in group A continued to receive their previous supplements while in group B, FA was substituted by calcium levofolinate 5 mg given orally every 48 hours. The following parameters were measured at baseline and at month 6: urea kinetic model and concentrations of plasma albumin, C-reactive protein, folate, vitamin B12, pyridoxal phosphate and tHcy. RESULTS: Group A: 30 patients aged 63.4 (57.9, 68.9) years, with a time on HD of 23.4 (15.8, 30.8) months, group B: 32 age-matched patients 66.2 (62.1, 70.3) years old, with a time on HD of 23.8 (16.7, 30.9) months. No differences were found either in folate levels (72.7 (47.9, 97.5) vs. 71.9 (44.0. 99.9) ng/ml), tHcy (23.5 (21.1, 25.9) vs. 23.3 (20.8, 25.8) micromol/l), or any other study variables. In the 2 groups a significant reduction in both residual renal function (RRF) and vitamin B12 levels was observed after supplementation, but no changes in tHcy values, folate levels or any of the other parameters were found. The prevalence of hyperhomocysteinemia in group A was 93.3% at study start and 100% at month 6, in group B the corresponding values were 93.8% and 96.9%. After 6 months, multiple regression analysis showed that tHcy levels were not influenced by the type of treatment (p = 0.543). CONCLUSIONS: After 6 months of calcium-levofolinate supplementation tHcy levels did not decrease and were similar to those in patients given the same dose of FA.     

Impact of high-flux/high-efficiency dialysis on folate and homocysteine metabolism

High-flux/high-efficiency (HF/HE) dialysis may have detrimental effects on micro-nutrients and water-soluble vitamins, such as vitamin B6, whose levels are lowered. Folate deficiency may increase cardiovascular risk through an increase in homocysteine (Hcy) serum levels. We therefore investigated the effects of dialysis with a high-flux (HF) membrane on folate and Hcy metabolism. Twelve patients without any folate supplementation, receiving dialysis with a low-flux membrane prior to the study (TO), were switched to dialysis using a HF triacetate membrane for four months (T1, T2, T3, T4) and received an oral daily folate supplementation during the two last months (T3, T4). Mean predialysis plasma folate levels fell dramatically after one month of HF dialysis (T1) and remained significantly lower than the initial level (p<0.05) at T2. Hcy concentrations were high in all patients at TO (mean 47.3 +/- 17.6 microM, normal range 5 to 15 microM). They did not change during the first two months of the study but dropped steeply after the beginning of oral folate supplementation. Folate supplementation should be used in HF/HE dialysis to avoid folate depletion. The combination of folate supplementation and HF/HE may lower Hcy levels and reduce cardiovascular morbidity and mortality in these patients.