NDT Advance Access originally published online on March 6, 2006
Nephrology Dialysis Transplantation 2006 21(7):1927-1933; 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
Original Articles: Dialysis and Transplantation
Effects of folinic acid on forearm blood flow in patients with end-stage renal disease
1 Department of Cardiovascular Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, 2 Division of Cardiovascular Surgery, University of Toronto and 3 Department of Medicine, Renal Division, University of Calgary, Canada
Correspondence and offprint requests to: Todd J. Anderson, MD, FRCPC, Division of Cardiology, 8th Floor, Foothills Hospital, 1403-29th Street NW, Calgary, Alberta T2N 2T9, Canada. Email: todd.anderson{at}calgaryhealthregion.ca
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