Effects of a vitamin E-bonded membrane and of glutathione on anemia and erythropoietin requirements in hemodialysis patients.
BACKGROUND
The oxidative damage of RBC membranes in hemodialysis (HD) patients increases red blood cell (RBC) susceptibility to hemolysis and impairs cell survival. Reduction of the oxidative stress might lead to better control of anemia and reduction of the erythropoietin (rhEPO) dose.


METHODS
We studied 38 stable HD patients, given a mean dose of rhEPO of 104+/-65 U/kg BW/week, at baseline and during antioxidant treatment with either a full or a 50% dose of EPO. Antioxidant treatment involved the combined use of glutathione, GSH (1200 mg i.v. at the end of each dialysis session) and a vitamin E-bonded HD membrane, CL-E. RBC and reticulocyte counts were done monthly. RBC survival (51Cr T/2) was assayed in 18 patients before and after the end of the study. Oxidative status was determined in 10 patients by measuring plasma concentrations of malondyhaldeide-4-hydroxynonenal (MDA-4HNE), reactive oxygen molecular species (ROMs), and oxydized-LDL (oxLDL) as indices of oxidative stress, alpha-tocopherol and total thiols as single antioxidants, and TAS as a marker of total antioxidant plasma activity.


RESULTS
Antioxidant treatment significantly reduced the high basal plasma concentrations of MDA4HNE and oxLDL, and significantly increased those of alpha-tocopherol, whereas TAS and thiols were unmodified. These changes lasted after the reduction of EPO. Anemia significantly improved with treatment, due to a significant increase in RBC survival. A close direct linear relationship was detected between plasma levels of vitamin E and hemoglobin.


CONCLUSIONS
Adequate control of oxidative stress achieves better control of anemia in HD patients. Since several antioxidant systems are impaired in uremia, the combined use of the CL-E membrane and GSH seems to be the best antioxidant therapy so far, with significant saving of the rhEPO dose.
Usberti
Mario
M
Nephrology and Dialysis Service, Manerbio Hospital, Brescia, Italy. mario.usberti@aod.it
Gerardi
Gianmario
G
Micheli
Annamaria
A
Tira
Paola
P
Bufano
Giuseppe
G
Gaggia
Paola
P
Movilli
Ezio
E
Cancarini
Giovanni C
GC
De Marinis
Sergio
S
D'Avolio
Gerolamo
G
Broccoli
Roberto
R
Manganoni
Annunciata
A
Albertin
Alberto
A
Di Lorenzo
Diego
D
D000328:Adult; D000368:Aged; D000747:Anemia, Hypochromic / Q000188:drug therapy* / Q000209:etiology; D000975:Antioxidants / Q000008:administration & dosage; D001774:Blood Chemical Analysis; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D005978:Glutathione / Q000008:administration & dosage*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011994:Recombinant Proteins; D012016:Reference Values; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014810:Vitamin E / Q000008:administration & dosage*
D000975:Antioxidants; D011994:Recombinant Proteins; D004921:Erythropoietin; D014810:Vitamin E; D005978:Glutathione