Effects of folinic acid on forearm blood flow in patients with end-stage renal disease.
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 microg/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 micromol/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.
Anderson
Todd J
TJ
Department of Cardiovascular Sciences, Lubin Cardiovascular Institute of Alberta, University of Calgary, Canada. todd.anderson@calgaryhealthregion.ca
Sun
Yiu-Hui
YH
Hubacek
Jaroslav
J
Hyndman
M Eric
ME
Verma
Subodh
S
Shewchuk
Lana
L
Scott-Douglas
Nairne
N
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D050197:Atherosclerosis; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005542:Forearm; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000473:pathology*; D002955:Leucovorin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010919:Placebos; D012039:Regional Blood Flow / Q000187:drug effects*; D013997:Time Factors; D014803:Vitamin B Complex / Q000494:pharmacology*
D010919:Placebos; D014803:Vitamin B Complex; D009599:Nitroprusside; D005492:Folic Acid; D000109:Acetylcholine; D002955:Leucovorin