Abstract Hyperhomocysteinemia, a risk factor for vas- cular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include de- ficiencies in folate and vitamin B 12 , methylenetetrahy- drofolate reductase (MTHFR) genotype and renal func- tion. 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 μmol/l vs 6.8 μmol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 μmol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concen- trations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B 12 was similar in pa- tients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteine- mia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma ho- mocysteine (28.5 μmol/l) than nondialyzed patients with the mutation (10.7 μmol/l), P<0.002. In our study, differ- ences between controls and patients in plasma homocys- teine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B 12 less than 522 pmol/l. Our study shows that hyper- homocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B 12 status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are par- ticularly at risk for hyperhomocysteinemia. Further stud- ies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients. Keywords Plasma homocysteine concentration · Vitamin B 12 · Folic acid · MTHFR genotype · Chronic renal failure Introduction Homocysteine is a thiol-containing amino acid derived from the metabolism of methionine. It is metabolized through the transsulfuration pathway by cystathionine-β- synthase (CBS) to form cysteine or remethylated to form methionine by methionine synthase (MS), a reaction that is dependent on the cofactor vitamin B 12 . Methylenetet- rahydrofolate reductase (MTHFR) synthesizes the folate derivative that provides the methyl group for the methio- nine synthase reaction. Disorders of homocysteine metabolism resulting in hyperhomocysteinemia can be caused by genetic and nongenetic factors. Severe genetic deficiencies of CBS and MTHFR activity (homocystinuria) are rare. The most common form of genetic hyperhomocysteinemia results from production of a thermolabile variant of MTHFR with moderately reduced enzyme activity [1]. Homozy- gosity for this polymorphism occurs in 10%–12% of the general North American population and is associated with increased plasma homocysteine concentration in subjects with low folate [2]. Nongenetic causes of hyper- homocysteinemia include dietary deficiencies of folate and vitamin B 12 [3] and chronic renal failure [4, 5]. A. Merouani ( ✉ ) · M. Lambert · P. Robitaille Department of Pediatrics, Ste-Justine Hospital, University of Montréal, 3175 Cote Sainte-Catherine, Montréal, Canada, H3T1C5 e-mail: merouana@ere.umontreal.ca Tel.: +1-514-3454737, Fax: +1-514-3454838 E.E. Delvin Department of Clinical Biochemistry, Ste-Justine Hospital, University of Montréal, Montréal, Canada J. Genest, Jr. Division of Cardiology, McGill University Health Center, Royal Victoria Hospital, Montréal, Canada R. Rozen Departments of Pediatrics and Human Genetics, McGill University Health Center, Montréal, Canada Pediatr Nephrol (2001) 16:805–811 © IPNA 2001 ORIGINAL ARTICLE Aicha Merouani · Marie Lambert · Edgar E. Delvin Jacques Genest, Jr. · Pierre Robitaille · Rima Rozen Plasma homocysteine concentration in children with chronic renal failure Received: 26 January 2001 / Revised: 16 April 2001 / Accepted: 17 April 2001