Hyperhomocysteinaemia and MTHFR C677T gene polymorphism in renal transplant recipients

Abstract

Aim-To study the eVect of folate treatment on hyperhomocysteinaemia and the eVect of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism on total homocysteine and folate concentrations after renal transplantation. Methods-A total of 30 transplanted children and adolescents were investigated for total homocysteine and folate serum concentrations before and after folate treatment, as well as for the presence of the MTHFR C677T polymorphism. Results-The allele frequency of C677T polymorphism in the MTHFR gene in the study population (0.33) was not diVerent to that in controls (0.38). Before folate treatment the homocysteine concentration was raised in all groups; following folate supplementation it was significantly decreased in the CC and CT groups, but not in the TT group. In patients with CC genotype, serum homocysteine correlated with serum creatinine and cholesterol, and time since transplantation before treatment. Conclusion-Folate supplementation appears to be an eVective strategy to normalise total homocysteine concentration in renal transplanted children and adolescents. (Arch Dis Child 2001;85:47-49)

Autonomic dysfunction in uremia assessed by heart rate variability

“…Between 15 and 30 years of age, the incidence of cardiovascular death is about two orders of magnitude higher in HD patients compared with the general population [1,2,3]. A number of possible mechanisms have been proposed to explain the excess of cardiovascular mortality, including hypertension, anemia, inflammation, and increased arterial stiffness due to disturbed calcium, phosphate, homocysteine, and lipid metabolism [4,5,6,7,8,9]. Recently, the role of cardiovascular autonomic dysfunction has been emphasized as an independent risk factor for sudden cardiac death in uremia [3,10].…”

Hyperhomocysteinemia in children with renal transplants

“…It has been suggested that plasma cyclosporine A levels may alter plasma tHcys concentration [33], but recent trials have failed to corroborate such an influence [34,35]. Homozygosity for the MTHFR C677T polymorphism constitutes an important determinant of plasma tHcys levels both in children with end-stage renal failure [19] and recipients of renal transplants [20]. This polymorphism results in decreased enzyme activity and decreased formation of active folate [24].…”

“…It is already present in 60%-90% of children with chronic renal insufficiency [18,19] and persists after renal transplantation [18,20], albeit at lower levels, despite the improvement in renal function. In this series, hyperhomocysteinemia was present in 73% of patients.…”

“…The beneficial effect of folic acid supplementation is also evident both in adults and in children on dialysis or with renal transplants [20,39,40,41,42]. The dosage of folic acid for optimal treatment in children is not yet established, but a dose of 2.5 or 5 mg/day, depending on age, is generally prescribed.…”

“…In transplanted adults, the MTHFRR polymorphisms also influence plasma tHcys [15,16,17]. Only a few reports have recently demonstrated that hyperhomocysteinemia may be also present in children with chronic renal failure or recipients of renal transplants [18,19,20].…”