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NDT Advance Access published online on March 6, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl083
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received January 31, 2006
Accepted February 7, 2006

Original Article

Effects of folinic acid on forearm blood flow in patients with end-stage renal disease

Todd J. Anderson 1 *, Yiu-Hui Sun 1, Jaroslav Hubacek 1, M. Eric Hyndman 1, Subodh Verma 2, Lana Shewchuk 1, and Nairne Scott-Douglas 3

1 Department of Cardiovascular Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Canada
2 Division of Cardiovascular Surgery, University of Toronto, Canada
3 Department of Medicine, Renal Division, University of Calgary, Canada

* To whom correspondence should be addressed.
Todd J. Anderson, E-mail: todd.anderson{at}calgaryhealthregion.ca



  Abstract

Background. Abnormalities of endothelial function are likely to contribute to the accelerated atherosclerotic risk in subjects with end-stage renal disease (ESRD). While folates can improve endothelial function, their role in ESRD has not been fully studied. The objective was to determine the acute and 12 week-effect of folinic acid on endothelium-dependent vasodilation in subjects with ESRD.

Methods. Forearm blood flow (FBF) was assessed by strain gauge plethysmography at baseline and after 12 weeks in 34 ESRD patients (57±14 years). Vascular function was assessed with acetylcholine (ACh), and sodium nitroprusside (SNP). Patients were randomized to receive folinic acid (50 mg i.v. once weekly) or a matching placebo. A subset of 25 subjects also received folinic acid (500 µg/min intra-arterially) or placebo to determine the acute effect on ACh and SNP mediated dilation at the time of the baseline vascular study.

Results. Folinic acid acutely improved the maximum change in ACh mediated FBF (10.0±2.4 to 12.8±2.2 ml/min/100 ml, P = 0.017), but did not change SNP responses. Chronic active therapy did not change ACh or SNP-mediated increases in FBF. Folinic acid resulted in a non-significant decrease in homocysteine (21±6 vs 28±18 µmol/l, P = 0.16) and diastolic blood pressure was significantly reduced (P = 0.05).

Conclusions. The present study demonstrated that folinic acid acutely improved endothelium-dependent vasodilatation in patients with ESRD suggesting a direct vascular effect. Chronic treatment with folinic acid did not show benefit in endothelial function, but did lower diastolic blood pressure. Further work is required to determine the optimal regime to protect vascular health in subjects with ESRD.

Keywords: atherosclerosis; dialysis; endothelium; folates; renal disease.
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