Nephrology Dialysis Transplantation, Vol 13, Issue 3 656-661, Copyright © 1998 by Oxford University Press
F Loehrer, C Angst, F Brunner, W Haefeli and B Fowler
Background: Elevated homocysteine concentrations have
been associated with premature arteriosclerosis and with impairment of key
methylation reactions through accumulation of the homocysteine metabolite
S-adenosylhomocysteine. In end-stage renal failure high homocysteine
concentrations are commonly found but thus far the concentrations of
related adenosylated metabolites in plasma have not been assessed.
Methods: In this prospective study we determined
plasma homocysteine and related metabolites in 25 patients on regular
haemodialysis, and in 40 healthy volunteers. Blood samples from patients
were drawn immediately before and in 10 patients additionally after the
dialysis session. Results: Folic acid and vitamin B12
in plasma were similar in patients (mean±SEM 25±2
nmol/l and 400±41 pmol/l respectively) and controls
(24±3 and 324±23 respectively). In patients plasma
homocysteine, S-adenosylmethionine and S-adenosylhomocysteine were markedly
elevated (36.6±3.6 &mgr;mol/l, 381±32 nmol/l and
1074±55 nmol/l respectively) compared to the control values
(6.8±0.4 &mgr;mol/l, 60±3 nmol/l and
24.4±1.2 nmol/l respectively) whereas the molar ratio of plasma
S-adenosylmethionine and S-adenosylhomocysteine was significantly decreased
(0.36±0.02 and 2.7±0.2 in patients and controls
respectively). Haemodialysis failed to normalize the abnormal levels of
these metabolites. Conclusion: Since the ratio of
S-adenosylmethionine : S-adenosylhomocysteine is closely linked to the
activity of numerous enzymatic methylation reactions, these results suggest
that methylation may be impaired in these patients. Key
words: S-adenosylhomocysteine; S-adenosylmethionine;
cardiovascular disease; end-stage renal disease; homocysteine; methylation
ORIGINAL ARTICLES
Evidence for disturbed S-adenosylmethionine: S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions?
Metabolic Unit, University Children's Hospital Basel, CH-4005 Basel, Switzerland; Division of Nephrology and Division of Clinical Pharmacology, Department of Medicine, University Hospital, Basel, Switzerland; Department of Pharmacy, University of Basel, Switzerland; Corresponding author
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