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NDT Advance Access originally published online on May 9, 2008
Nephrology Dialysis Transplantation 2008 23(10):3272-3279; doi:10.1093/ndt/gfn254
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Reduction of the genomic damage level in haemodialysis patients by  folic acid and vitamin B12 supplementation

Helga Stopper1, Anna-Teresa Treutlein1, Udo Bahner2, Nicole Schupp1, Ursula Schmid1, Andreas Brink1, Alessandra Perna3 and August Heidland2

1 Department of Toxicology 2 Department of Internal Medicine, University of Wuerzburg, Wuerzburg, Germany 3 First Division of Nephrology, Interdepartmental Center for Clinical Research, Second University of Naples, Naples, Italy

Helga Stopper, Department of Toxicology, University of Wuerzburg, Versbacher Strasse 9, D-97078 Wuerzburg, Germany. Tel: +49-931-201-48427; Fax: +49-931-201-48446; E-mail: stopper{at}toxi.uni-wuerzburg.de



  Abstract

Background. Cancer incidence and genomic damage of peripheral lymphocytes are elevated in patients with end-stage renal failure. Among other uraemic toxins, homocysteine (Hcy) levels are increased in most of these patients. In healthy individuals, plasma Hcy correlates with the degree of genomic damage observed in peripheral blood lymphocytes (PBL). The accumulation of Hcy can be reduced by supplementation with folic acid and vitamin B12. The aim of this study was to analyse whether this supplementation can also lower the genomic damage in PBL of haemodialysis patients. This may ultimately help to reduce cancer incidence in renal patients.

Methods. In a prospective study with 27 patients, we analysed the genomic damage in dialysis patients before and at different time points after the initiation of folate/vitamin B12 supplementation. Genomic damage was measured by the frequency of micronuclei, a subset of chromosomal aberrations, in PBL.

Results. Supplementation with folic acid and vitamin B12 (more markedly with both) reduced the micronucleus frequency in PBL of dialysis patients. This was not mediated by altered lymphocyte proliferation capacity or changes in DNA cytosine-methylation. Plasma-Hcy was lowered more efficiently by the combined folic acid/vitamin B12 supplementation, and lymphocyte DNA of this group exhibited a nonsignificant trend for a reduction of 1,N6-etheno-2'-deoxyadenosine, a marker for oxidative stress.

Conclusions. A reduction of the genomic damage in PBL can be achieved in dialysis patients by supplementation with folic acid and vitamin B12. This may be mediated by Hcy reduction.

Keywords: dialysis; folic acid; homocysteine; micronuclei; vitamin B12

Received for publication: 16.11.07
Accepted in revised form: 14. 4.08


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