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Homocysteine, folate, vitamin B12 levels, and C677T MTHFR mutation in children with renal failure

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Abstract

Hyperhomocysteinemia is well documented in chronic renal failure (CRF) and premature and progressive occlusive vascular disease is common in CRF. The combined effects of renal failure, folate and vitamin B12 levels, and a common mutation (C677T) in the methylenetetrahydrofolate reductase (MTHFR) gene that leads to total plasma homocysteine (tHcy) elevation in CRF children were investigated. Forty-two children (15 females) with CRF, mean age 10.3±4.7 years, were included. The mean glomerular filtration rate (GFR) was 37.3±16.9 ml/min per 1.73 m2. The control group comprised 33 children (18 females) with a mean age of 8.6±3.4 years. There were 40% of CRF patients with hyperhomocysteinemia. Folate and vitamin B12 deficiencies were identified in 14% (n=6) and 5% (n=2), respectively, of all patients. On univariate analysis, the tHcy serum concentration was negatively correlated with the plasma folate concentration (P<0.05) in controls, and with GFR (P<0.05) in patients. On multiple regression analysis for the predictors of tHcy serum concentrations, folic and vitamin B12 were significant in controls, whereas only GFR was significant in CRF children. In our patients no effect of the MTHFR polymorphism on tHcy levels was seen This result, in addition to the limited number of patients, may partially be explained by the low prevalence of folate deficiency in our patients.

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References

  1. Graham IM, Daly LE, Refsum HM (1997) Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 277:1775–1781

    CAS  PubMed  Google Scholar 

  2. Fodinger M, Buchmayer H, Sunder-Plassmann G (1999) Molecular genetics of homocysteine metabolism. Miner Electrolyte Metab 25:269–278

    Article  CAS  PubMed  Google Scholar 

  3. Kang SS, Wong PW, Susmano A, Sora J, Norusis M, Ruggie N (1991) Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. Am J Hum Genet 48:536–545

    CAS  Google Scholar 

  4. Finkelstein JD, Martin JJ (1986) Methionine metabolism in mammals. Adaptation to methionine excess. J Biol Chem 261:1582–1587

    CAS  PubMed  Google Scholar 

  5. Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, Maemura K, Shindo T, Minamino T, Ohno M, Yamaoki K, Ogasawara K, Aizawa T, Suzuki S, Yazaki Y (1997) Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation 95:2032–2036

    CAS  PubMed  Google Scholar 

  6. Brattstrom L (1997) Common mutation in the methylenetetrahydrofolate reductase gene offers no support for mild hyperhomocysteinemia being a causal risk factor for cardiovascular disease. Circulation 96:3805–3807

    CAS  PubMed  Google Scholar 

  7. Bostom AG, Shemin D, Lapane KL, Nadeau MR, Sutherland P, Chan J, Rozen R, Yoburn D, Jacques PF, Selhub J, Rosenberg IH (1996) Folate status is the major determinant of fasting total plasma homocysteine levels in maintenance dialysis patients. Atherosclerosis 123:193–202

    CAS  PubMed  Google Scholar 

  8. Bostom AG, Culleton BF (1999) Hyperhomocysteinemia in chronic renal disease. J Am Soc Nephrol 10:891–900

    CAS  PubMed  Google Scholar 

  9. Massy ZA (1999) Reversal of hyperhomocyst(e)inaemia in chronic renal failure—is folic or folinic acid the answer? Nephrol Dial Transplant 14:2810–2812

    Article  CAS  PubMed  Google Scholar 

  10. Fodinger M, Mannhalter C, Wolfl G, Pabinger I, Muller E, Schmid R, Horl WH, Sunder-Plassmann G (1997) Mutation (677 C to T) in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients. Kidney Int 52:517–523

    CAS  PubMed  Google Scholar 

  11. Lilien M, Duran M, Van Hoeck K, Poll-The BT, Schroder C (1999) Hyperhomocyst(e)inaemia in children with chronic renal failure. Nephrol Dial Transplant 14:366–368

    CAS  PubMed  Google Scholar 

  12. Schroder CH, Wan de Boer A, Giesen AM, Monnens LAH, Blom H (1999) Treatment of hyperhomocysteinemia in children on dialysis by folic acid. Pediatr Nephrol 13:583–585

    PubMed  Google Scholar 

  13. Litwin M, Abuauba M, Wawer ZT, Grenda R, Kuryt T, Pietraszek E (2001) Folate, vitamin B12, and sulfur amino acid levels in patients with renal failure. Pediatr Nephrol 16:127–132

    Article  CAS  PubMed  Google Scholar 

  14. Merouani A, Lambert M, Delvin EE, Genest J Jr, Robitaille P, Rozen R (2001) Plasma homocysteine concentration in children with chronic renal failure. Pediatr Nephrol 16:805–811

    CAS  PubMed  Google Scholar 

  15. Maroni BJ, Steinman TI, Mitch WE (1985) A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int 27:58–65

    CAS  PubMed  Google Scholar 

  16. Minniti G, Piana A, Armani U, Cerone R (1998) Determination of plasma and serum homocysteine by high-performance liquid chromatography with fluorescence detection. J Chromatogr A 828:401–405

    Article  CAS  PubMed  Google Scholar 

  17. Guldener C van, Donker AJ, Jakobs C, Teerlink T, Meer K de, Stehouwer CD (1998) No net renal extraction of homocysteine in fasting humans. Kidney Int 54:166–169

    PubMed  Google Scholar 

  18. Suliman ME, Lindholm B, Barany P, Bergstrom J (2001) Hyperhomocysteinemia in chronic renal failure patients: relation to nutritional status and cardiovascular disease. Clin Chem Lab Med 39:734–738

    CAS  PubMed  Google Scholar 

  19. Cuskelly GJ, Stacpoole PW, Williamson J, Baumgartner TG, Gregory JF 3rd (2001) Deficiencies of folate and vitamin B(6) exert distinct effects on homocysteine, serine, and methionine kinetics. Am J Physiol Endocrinol Metab 281:E1182–E1190

    CAS  PubMed  Google Scholar 

  20. Kimura H, Gejyo F, Suzuki S, Miyazaki R (2000) The C677T methylenetetrahydrofolate reductase gene mutation in hemodialysis patients. J Am Soc Nephrol 11:885–893

    CAS  PubMed  Google Scholar 

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Correspondence to Alberto Canepa.

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Canepa, A., Carrea, A., Caridi, G. et al. Homocysteine, folate, vitamin B12 levels, and C677T MTHFR mutation in children with renal failure. Pediatr Nephrol 18, 225–229 (2003). https://doi.org/10.1007/s00467-002-1058-0

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  • DOI: https://doi.org/10.1007/s00467-002-1058-0

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