Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy.
OBJECTIVE
Haemodialysis patients have elevated levels of the atherogenic amino acid homocysteine. We wanted to assess the effects of small doses of intravenous folinic acid (the active form of folic acid) on some biochemical risk factors of cardiovascular disease.


METHODS
Longitudinal and open intervention study.


METHODS
Two dialysis units in the County of Rogaland.


METHODS
All patients on maintenance haemodialysis were invited, and 32 of 35 patients gave their informed consent.


METHODS
After each dialysis session, the patients were given 1.0 mg of folinic acid intravenously thrice a week for a period of 3 months. Prior to and during the study, all patients were on maintenance supplementation with small doses of vitamins B1, B2, B3, B5, B6 and B12.


METHODS
Changes in the levels of (i) plasma total homocysteine (p-tHcy) and folate, (ii) circulating endothelium related proteins--markers of endothelial activation and (iii) serum malondialdehyde (S-MDA)--a marker of oxidative stress and lipid peroxidation.


RESULTS
The p-tHcy levels were reduced by 37% (P < 0.0001), whilst the serum and erythrocyte folate levels increased by 95 and 104%, respectively (P < 0.0001 for both). The circulating levels of endothelium related cellular adhesion molecules and haemostatic factors remained high and unchanged, except the thrombomodulin (TM) levels increased (P = 0.0004). The high levels of S-MDA were reduced by 26% (P = 0.003).


CONCLUSIONS
Low doses of folinic acid given intravenously to dialysis patients reduced their levels of p-tHcy and S-MDA and thus improved their cardiovascular risk profile. The concurrent increment in TM levels was unexpected and of unknown clinical significance.
Apeland
T
T
Renal Unit, Department of Medicine, Rogaland Central Hospital, Stavanger, Norway. apeland@online.no
Mansoor
M A
MA
Seljeflot
I
I
Brønstad
I
I
Gøransson
L
L
Strandjord
R E
RE
D003404:Creatinine / Q000097:blood; D004730:Endothelium, Vascular; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D002955:Leucovorin / Q000008:administration & dosage*; D008137:Longitudinal Studies; D008297:Male; D008315:Malondialdehyde / Q000097:blood*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D006435:Renal Dialysis; D012709:Serum Albumin / Q000032:analysis
D006454:Hemoglobins; D012709:Serum Albumin; D006710:Homocysteine; D008315:Malondialdehyde; D003404:Creatinine; D002955:Leucovorin