Randomized trial of FX high flux vs standard high flux dialysis for homocysteine clearance

Abstract

Background. Cardiovascular disease is the major cause of death in the end-stage renal disease population. Novel risk factors such as homocysteine (Hcy) are of considerable interest in this group as hyperhomocysteinaemia is highly prevalent in the setting of renal impairment. Folic acid-vitamin B group therapies are only partially effective treatments. Hcy is highly protein-bound and thus poorly dialysed. Dialyzers with albumin-leaking properties have been shown to result in lowering of plasma Hcy. As the FX-class (Advanced Fresenius Polysulfone dialyzer) has greater clearance of larger molecular weight substances but is non-albumin-leaking, we explored the capacity of this new technology membrane to reduce plasma Hcy levels. Methods. A prospective randomized cross-over trial in 35 prevalent haemodialysis patients, one group receiving 12 weeks dialysis using FX dialyzer then 12 weeks with standard high flux dialysis (SHF) and the other group SHF followed by FX dialyzer. All patients received vitamin B 6 25 mg and folic acid 5 mg daily throughout the study. Results. The primary outcome was plasma Hcy pre-dialysis at week 12. FX vs SHF showed no significant difference, 25±6.6 vs 25.9±5.8 mg/l, Á95% CI ¼ À2.77 to 4.59, P ¼ 0.31. There was a nonsignificant trend toward a decrease in Hcy in both groups (27.43±7.68 to 25.91±5.78 mmol/l for SHF, P ¼ 0.23 and 26.0±4.58 to 25.0±6.61 mmol/l for FX, P ¼ 0.28). Analysis by repeated measures method demonstrated a statistically significantly lower Hcy with FX vs SHF dialyzer (adjusted b ¼ À1.30, 95% CI ¼ À2.41 to À0.19, P ¼ 0.022). K t /V urea was higher in FX vs SHF (1.35±0.18 vs 1.22±0.2; P ¼ 0.013). Folate and B 6 levels did not change. Conclusions. The primary outcome analysis did not show any significant difference in pre-Hcy comparing FX and SHF membranes. Although our secondary analysis demonstrated a statistically significant difference between membranes, the magnitude of the difference (1.3 mmol/l) is not clinically significant. Thus the use of the FX dialyzer did not result in a clinically significant benefit in relation to improving pre-dialysis Hcy compared with standard high-flux dialysis.

Washout of water‐soluble vitamins and of homocysteine during haemodialysis: Effect of high‐flux and low‐flux dialyser membranes

“…Also, treatment with nocturnal haemodialysis is independently associated with lower tHcy levels before dialysis 27 . However, the use of FX‐class dialysers, which have a better clearance of larger uraemic toxins than standard high‐flux dialysers but are non‐albumin‐leaking, did not result in a clinically significant benefit with regard to improved predialysis concentrations of tHcy 28 …”

“…27 However, the use of FX-class dialysers, which have a better clearance of larger uraemic toxins than standard high-flux dialysers but are non-albumin-leaking, did not result in a clinically significant benefit with regard to improved predialysis concentrations of tHcy. 28 Although this is a non-randomized trial with a relatively small number of patients in the treatment groups, which are not balanced regarding age and time on dialysis, it can be summarized that blood concentrations of water-soluble vitamins are reduced by the dialysis procedure. The nature of the dialysis membranes, high-flux or low-flux, has no influence on washout of vitamins.…”

Effect of FX Dialysers on Systemic Inflammation and Quality of Life in Chronic Haemodialysis Patients

“…Detailed studies on the potential clinical benefits, however, have Some studies have demonstrated a reduced CRP, oxidized LDL cholesterol and pentosidine levels, suggesting a reduction in inflammation and oxidative stress, but these were performed comparing high-flux to low-flux dialysers unlike our study which is comparing two different high-flux dialysers to each other [11,14,15] . Previous studies on the FX class of dialyser have demonstrated no significant change in serum homocysteine level, parameters of oxidative stress or inflammation compared to use of a HF80 dialyser [16,17] .…”

Homocysteine and Folate Therapy in Dialysis Patients

“…High-flux dialysers with high capacity to eliminate large uraemic substances, but without excessive leakage of useful proteins such as albumin, show a larger intradialytic hcy reduction rate, about 40% compared to 30% with low-flux membrane, but pre-dialysis hcy values are slightly, but not significantly, lower with high-flux membranes compared to low flux dialysers after 3 months of follow-up [37]. Advanced high-flux polysulphone dialysers with great clearance of larger uraemic toxins, but nonalbumin-leaking, do not improve hcy clearance compared to standard high-flux polysulphone membranes, confirming that the major part of uraemic toxins affecting hcy metabolism are protein-bound or have a molecular weight above 15000 Daltons [38]. Super-flux, albumin-leaking, dialysers improve pre-dialysis plasma hcy concentrations compared to both low and high-flux membranes, mainly by removing large molecular weight solutes able to affect the hcy metabolism [39,40,41].…”