Jungers P, Chauveau P, Chadefaux B, Aupetit J, Labrunie M,
Descamps-Latscha B, Kamoun P
Hyperhomocysteinemia is associated with arterial occlusive
accidents in predialysis chronic renal failure patients
Am Soc Nephrol
J Am Soc Nephrol (abstract)
(Sep) 7:1320 1996
Also reviewed: Folate status, a common mutation in methylene
tetrahydrofolate reductase and fasting total plasma homocysteine levels in
dialysis patients by Bostom et al., JASN 7:1474, 1996.
Homocysteine is an intermediary amino acid formed during the
interconversion of methionine and cysteine. Transsulfuration of
homocysteine to cysteine requires vitamin B6 as a cofactor while
remethylation of homocysteine to methionine requires folate and
vitamin B12 as cofactors. Multiple lines of evidence have documented
an association between elevated levels of homocysteine and
cardiovascular events such as stroke and myocardial infarction in the
general population.
The levels of homocysteine in patients with
chronic renal failure and in patients receiving maintenance dialysis
have been reported to be elevated due to decreased removal by the
kidneys and due to disorders in metabolism. In addition, the most common
enzyme defect associated with hyperhomocysteinemia involves the enzyme
methylene tetrahydrofolate reductase (MTHFR). It has also has been
demonstrated that providing dietary supplements of folate, B6 and B12
can lower elevated levels of homocysteine. One mutation of MTHFR
leads to high levels of homocysteine when folate levels are low. Two
abstracts examined homocysteine levels in patients with chronic renal
failure.
Bostom et al demonstrated that the above mentioned mutation in MTHFR
occurs with a homozygous frequency of 13% and a heterozygous frequency
of 44% in 68 patients on maintenance dialysis. Importantly, patients
with folate levels above 29 ng/ml had lower homocysteine levels than
those with levels below this value after accounting for a number of
variables including age, sex , levels of B6 and B12, creatinine and
albumin. In persons with normal renal function, these investigators
had previously determined that folate levels of less than 6.8 ng/ml
were associated with higher levels of homocysteine. The implication
of this study is that supernormal levels of folate are still
associated with high levels of homocysteine in patients on maintenance
hemodialysis and that current dosages of folate supplementation may be
inadequate to lower homocysteine levels in those patients with
elevated levels who are at risk for cardiovascular events.
Jungers et al have performed the first prospective study examining the
risk of arterial occlusive events in association with elevated
homocysteine levels in patients with chronic renal failure. In 93
patients with a GFR < 50 ml/min and older than 50 years of age, 24
experienced a myocardial infarction, or stroke over a 5 year period of
study. There was no difference in age or serum creatinine between
this group and the 69 patients who did not experience an arterial
occlusive event. However, there were very significant differences in
homocysteine levels between the groups (20.7 mmol/L vs 12.8 mmol/L);
and the percentage of individuals with abnormal levels of greater
than 14 mmol/L was also highly significant (83% vs 30%). Thus,
elevated homocysteine levels represent a risk factor in patients with
chronic renal failure.
(Gerald Schulman, M.D., Vanderbilt University, Nashville, TN)
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Am Soc Nephrol
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