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 micromol/l), while in the study group at 1, 3, and 6 months they decreased from a baseline value (in micrormol/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 (delta hdhcy) slightly but progressively decreased during the 3 steps on protein-leaking dialyzers and a positive correlation was found between delta hdhcy 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 delta hdhcy 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.