Therapy of hyperhomocysteinemia in hemodialysis patients: effects of folates and N-acetylcysteine.
OBJECTIVE
Uremia represents a state where hyperhomocysteinemia is resistant to folate therapy, thus undermining intervention trials' efficacy. N-acetylcysteine (NAC), an antioxidant, in addition to folates (5-methyltetrahydrofolate, MTHF), was tested in a population of hemodialysis patients.


METHODS
The study is an open, parallel, intervention study.


METHODS
Ambulatory chronic hemodialysis patients.


METHODS
Clinically stable chronic hemodialysis patients, on hemodialysis since more than 3 months, undergoing a folate washout. Control group on standard therapy (n = 50).


METHODS
One group was treated with intravenous MTHF (MTHF group, n = 48). A second group was represented by patients treated with MTHF, and, during the course of 10 hemodialysis sessions, NAC was administered intravenous (MTHF + NAC group, n = 47).


METHODS
Plasma homocysteine measured before and after dialysis at the first and the last treatment.


RESULTS
At the end of the study, there was a significant decrease in predialysis plasma homocysteine levels in the MTHF group and MTHF + NAC group, compared with the control group, but no significant difference between the MTHF group and MTHF + NAC group. A significant decrease in postdialysis plasma homocysteine levels in MTHF + NAC group (10.27 ± 0.94 μmol/L, 95% confidence interval: 8.37-12.17) compared with the MTHF group (16.23 ± 0.83, 95% confidence interval: 14.55-17.90) was present. In the MTHF + NAC group, 64% of patients reached a postdialysis homocysteine level <12 μmol/L, compared with 19% in the MTHF group and 16% in the control group.


CONCLUSIONS
NAC therapy induces a significant additional decrease in homocysteine removal during dialysis. The advantage is limited to the time of administration.
First Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, Second University of Medicine, Naples, Italy. alessandra.perna@unina2.it
Alessandra F
AF
Perna
Eleonora
E
Violetti
Diana
D
Lanza
Immacolata
I
Sepe
Guido
G
Bellinghieri
Vincenzo
V
Savica
Domenico
D
Santoro
Ersilia
E
Satta
Giovanni
G
Cirillo
Antonio
A
Lupo
Cataldo
C
Abaterusso
Ilaria
I
Raiola
Paolino
P
Raiola
Salvatore
S
Coppola
Biagio
B
Di Iorio
Giuseppina
G
Tirino
Massimo
M
Cirillo
Diego
D
Ingrosso
Natale G
NG
De Santo
D000111:Acetylcysteine / Q000008:administration & dosage*; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D006710:Homocysteine; C032418:5,11-methenyltetrahydrohomofolate; D005492:Folic Acid; D000111:Acetylcysteine