The effect of PMMA-based protein-leaking dialyzers on plasma homocysteine levels

Abstract

Background. Hyperhomocysteinemia is a well-recognized independent risk factor for cardiovascular disease in end-stage renal disease (ESRD) patients. Since homocysteine (Hcy) largely binds to serum proteins (80 to 90%), in this study we investigated the possibility that polymethylmethacrylate (PMMA)-based protein-leaking dialyzers could reduce total plasma Hcy (tHcy) levels in ESRD patients. Methods. Two matched groups of patients (N = 13) showing mild to intermediate hyperhomocysteinemia on standard hemodialysis (HD) with conventional non-protein-leaking dialyzers were included. In the control group membranes were maintained the same, while the study group was switched to protein-leaking dialyzers (BK-F series; Toray, Japan) and studied for 6 months. tHcy was measured by high performance liquid chromatography (HPLC) at baseline and after 1, 3, and 6 months. Proteins and Hcy were also measured in the spent dialysate. Results. The pre-HD levels of tHcy in the control group remained close to baseline values (26.6 ± 5.0 μmol/L), while in the study group at 1, 3, and 6 months they decreased from a baseline value (in μmol/L) of 25.3 ± 5.9 to 21.5 ± 4.5, 16.9 ± 4.0, and 17.2 ± 4.2, respectively (P < 0.01 for values at 3 and 6 months vs. baseline). The intra-HD drop of tHcy (ΔHDHcy) slightly but progressively decreased during the 3 steps on protein-leaking dialyzers and a positive correlation was found between ΔHDHcy and pre-HD levels of tHcy. In spent dialysate samples from protein-leaking dialyzer-treated patients, the amount of protein-bound Hcy (bHcy) was approximately 10 times higher than in non-protein-leaking dialyzers, but the ΔHDHcy observed in non-protein-leaking dialyzers and protein-leaking dialyzers was comparable. Serum proteins and albumin were only slightly affected by protein-leaking dialyzers. Conclusion. This study demonstrates that protein-leaking dialyzers used with a pure diffusive technique significantly lower pre-HD tHcy (approximately 33% of starting levels after 3 months of treatment) in ESRD patients. A possible underlying mechanism for this effect could be the removal of large molecular weight solutes responsible for a defective metabolism of the Hcy, as the removal of bHcy with protein-leaking dialyzers seems not sufficient, per se, to explain this steady reduction of tHcy levels in pre-HD.