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


CONCLUSIONS
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.
Galli
Francesco
F
Department of Internal Medicine, Section of Applied and Clinical Biochemistry, University of Perugia, Italy. f.galli@unipg.it
Benedetti
Serena
S
Buoncristiani
Umberto
U
Piroddi
Marta
M
Conte
Carmela
C
Canestrari
Franco
F
Buoncristiani
Emanuela
E
Floridi
Ardesio
A
D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins; D015314:Dialysis Solutions; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000628:therapy*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D019904:Polymethyl Methacrylate / Q000627:therapeutic use*; D006435:Renal Dialysis / Q000379:methods*; D012709:Serum Albumin
D001798:Blood Proteins; D015314:Dialysis Solutions; D008567:Membranes, Artificial; D012709:Serum Albumin; D006710:Homocysteine; D019904:Polymethyl Methacrylate