Plasma homocysteine concentration in children with chronic renal failure

Abstract

Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 micromol/l vs 6.8 micromol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 micromol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B12 was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 micromol/l) than nondialyzed patients with the mutation (10.7 micromol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B12 less than 522 pmol/l. Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B12 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.

Study of the Homocysteine Status in Children with Chronic Renal Failure

“…In agreement with our results, Merouani et al [30]found higher levels of Hcy in dialysis patients than those on conservative treatment, whereas Hong et al [32]did not find any significant difference.…”

“…We found that Hcy in patients with CRF on conservative management did not differ from controls, similar to what was reported by Vilaseca et al [33]; however, other studies reported elevated levels in predialysis CRF [28, 29, 30, 34, 35, 36]. A negative correlation has been reported between Hcy level and GFR [35].…”

“…Our results revealed that basal serum Hcy levels were higher in children with ESRD on regular HD compared to controls or CRF patients on conservative therapy; similar higher levels of Hcy in HD patients in comparison to controls have been reported by some previous investigators [27, 28, 29, 30, 31]. In agreement with our results, Merouani et al [30]found higher levels of Hcy in dialysis patients than those on conservative treatment, whereas Hong et al [32]did not find any significant difference.…”

A hypothesis linking low folate intake to neural tube defects due to failure of post-translation methylations of the cytoskeleton

“…PEMT2 knockout mice develop normally, from a behavioral perspective, if given choline supplements, because extra phosphotidylcholine is produced via the alternate pathway of phosphorylation of choline. They do have some anatomical brain abnormalities even though their behaviour is normal (Merouani, et al, 2001).…”

Reduction of plasma homocysteine by folic acid in children with chronic renal failure

“…The association between moderately elevated homocysteine level and the increased risk of cardiovascular disease [2], as well as the amelioration of hyperhomocysteinemia by folic acid supplementation [2,3,4,5,6], has been reported in adults with predialytic chronic renal failure. However, only a few studies have examined changes in homocysteine level in children with predialytic chronic renal failure [7,8,9]. Furthermore, according to a recent literature search, no published data concerning the effect of vitamin supplementation on homocysteine levels in such children are available.…”