Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found
in adult patients with end-stage renal disease. Major determinants of elev
ated plasma homocysteine levels in these patients include deficiencies in f
olate and vitamin B-12, methylenetetrahydrofolate reductase (MTHFR) genotyp
e and renal function. Little information is available for children with chr
onic renal failure (CRF). The prevalence and the factors that affect plasma
homocysteine concentration were determined in children. Twenty-nine childr
en with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) wer
e compared with 57 age- and sex-matched healthy children. Homocysteine conc
entrations were higher in patients than controls (17.3 mu mol/l vs 6.8 mu m
ol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14
.0 mu mol/l) was seen in 62.0% of patients and 5.2% of controls. Folate con
centrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l)
, P<0.01. Vitamin B-12 was similar in patients (322 pmol/l) and controls (2
84 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteine
mia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mu
tation have higher plasma homocysteine (28.5 <mu>mol/l) than nondialyzed pa
tients with the mutation (10.7 mu mol/l), P<0.002. In our study, difference
s between controls and patients in plasma homocysteine concentrations are o
bserved when age is greater then 92 months, folate less than 21.6 nmol/l an
d vitamin B-12 less than 522 pmol/l. Our study shows that hyperhomocysteine
mia is common in children with CRF and is associated with low folate and no
rmal vitamin B-12 status, compared to normal children. Among the patients,
the dialyzed patients with the MTHFR mutation are particularly at risk for
hyperhomocysteinemia. Further studies are needed to investigate therapeutic
interventions and the potential link with vascular complications in these
patients.