Effects of erythropoietin and vitamin E-modified membrane on plasma oxidative stress markers and anemia of hemodialyzed patients.
BACKGROUND
Oxidant stress has a pathogenic role in uremic anemia, possibly interfering with erythropoietin (EPO) function and red blood cell (RBC) survival. Therefore, it is expected that antioxidant therapy might exert a beneficial effect on these parameters.


METHODS
To test this hypothesis, we investigated some oxidant stress indices, anemia levels, and RBC survival in 47 hemodialysis (HD) patients randomly assigned to three groups. Patients in groups A (n = l8) and B (n = 20) were on dialysis therapy using conventional cellulosic and synthetic membranes and were administered high and low doses of recombinant human EPO (rHuEPO), respectively. Patients in group C (n = 9) were dialyzed with vitamin E-modified membranes (CL-Es) and investigated in a two-step prospective study. In step Cl, patients were administered rHuEPO doses similar to those of group A. In step C2, rHuEPO doses were reduced to those of group B. As oxidant stress markers, we determined in plasma the susceptibility of lipids to undergo iron-catalyzed oxidation (reactive oxygen molecules [ROMs] test) and malondialdehyde-4-hydroxynonenal (MDA-4HNE), alpha-tocopherol (alpha-T), total thiol (-SH), and total antioxidant activity. RBC survival was measured using the chromium 51 T/2 technique in 22 patients.


RESULTS
Results show that: (1) high rHuEPO doses (groups A and C1) were associated with decreased ROM production, low alpha-T levels, and slightly increased -SH levels compared with corresponding groups on low rHuEPO doses (groups B and C2); (2) treatment with CL-Es (group C) increased plasma alpha-T and decreased -SH levels; these data were associated with decreased indices of lipid peroxidation, particularly MDA-4HNE 1evels, only in patients administered low rHuEPO doses; (3) alpha-T concentration influenced RBC survival, which was remarkably decreased in HD patients; patients treated with CL-Es showed a better degree of anemia correction; and (4) alpha-T level correlated negatively with -SH level and seemed to be independent of the extent of peroxidation and oxidizability of plasma lipids.


CONCLUSIONS
Both EPO and CL-E can influence plasma antioxidants and, to an extent, lipid peroxidation processes. However, this study shows that even in patients treated with low rHuEPO doses, RBC survival close to normal and sufficient correction of anemia are achieved only when appropriate alpha-T levels are reached.
Servizio di Nefrologia e Dialisi Ospedale di Manerbio, Manerbio, Bs, Italy. mario.usberti@aod.it
Mario
M
Usberti
GianMario
G
Gerardi
Giuseppe
G
Bufano
Paola
P
Tira
Annamaria
A
Micheli
Alberto
A
Albertini
Ardesio
A
Floridi
Diego
D
Di Lorenzo
Francesco
F
Galli
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002470:Cell Survival / Q000187:drug effects; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000628:therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011446:Prospective Studies; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000295:instrumentation* / Q000379:methods; D014511:Uremia / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D014810:Vitamin E / Q000378:metabolism*
D000975:Antioxidants; D015415:Biomarkers; D008567:Membranes, Artificial; D011994:Recombinant Proteins; D004921:Erythropoietin; D014810:Vitamin E