Effects of pre- vs. intra-dialysis folic acid on arterial wave reflections and endothelial function in patients with end-stage renal disease

Yuka Tochihara, Malcolm J Whiting, Jeffrey A Barbara, Arduino Aleksander Mangoni

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BACKGROUND: Haemodialysis (HD) is associated with the acute loss through the dialysis membrane of biochemical factors either enhancing [folic acid (F)] or impairing [asymmetric dimethylarginine (ADMA)] arterial function. Changes in these opposing factors might explain the absence of significant modifications in arterial function during HD. We speculated that intra-HD, instead of pre-HD, F administration would provide beneficial effects on arterial wave reflections and endothelial function by preventing HD-induced F loss. METHODS: Arterial wave reflections [augmentation index (AIx), pulse-wave analysis], endothelium-dependent vasodilation (salbutamol-mediated changes in AIx) and plasma concentrations of F and ADMA were measured pre-HD and end-HD in 10 patients (age 67.7 +/- 10.3 years). Each subject received F 5 mg either pre-HD or intra-HD in two separate studies 2-4 weeks apart, in an open-label randomized cross-over trial. RESULTS: Pre-HD F administration did not prevent significant reductions in F during HD (end-HD vs. pre-HD, -865 +/- 465 nmol l(-1), P <0.001), but no significant changes in AIx (+1.4 +/- 5.7%) or salbutamol-mediated AIx modifications (+0.4 +/- 5.5%) were observed. By contrast, intra-HD F administration was associated with significant increases in F (+298 +/- 283 nmol l(-1), P = 0.010) and a significant reduction of AIx (-4.7 +/- 7.2%, P = 0.013), but no effects on salbutamol-mediated AIx changes (+1.5 +/- 4.4%). There was a trend towards greater HD-induced reductions in plasma ADMA concentrations with intra-HD F administration (P = 0.066). CONCLUSIONS: Intra-HD F administration reduces arterial wave reflections but not endothelial function during HD. Given the prognostic significance of arterial wave reflections in HD patients, the timing of F administration is important in the design of interventional trials in this cohort.
Original languageEnglish
Pages (from-to)717-722
Number of pages6
JournalBritish Journal of Clinical Pharmacology
Volume66
Issue number5
Early online date11 Jul 2008
DOIs
Publication statusPublished - Nov 2008

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Folic Acid
Chronic Kidney Failure
Renal Dialysis
Dialysis
Albuterol
Pulse Wave Analysis
Vasodilation
Cross-Over Studies

Keywords

  • aged
  • albuterol
  • arginine
  • cross-over studies
  • drug administration schedule
  • endothelium, vascular
  • female
  • folic acid
  • humans
  • kidney failure, chronic
  • male
  • middle aged
  • radial artery
  • renal dialysis
  • statistics, nonparametric
  • vasodilator agents
  • arterial wave reflection
  • endothelial function
  • haemodialysis

Cite this

Effects of pre- vs. intra-dialysis folic acid on arterial wave reflections and endothelial function in patients with end-stage renal disease. / Tochihara, Yuka; Whiting, Malcolm J; Barbara, Jeffrey A; Mangoni, Arduino Aleksander.

In: British Journal of Clinical Pharmacology, Vol. 66, No. 5, 11.2008, p. 717-722.

Research output: Contribution to journalArticle

Tochihara, Yuka ; Whiting, Malcolm J ; Barbara, Jeffrey A ; Mangoni, Arduino Aleksander. / Effects of pre- vs. intra-dialysis folic acid on arterial wave reflections and endothelial function in patients with end-stage renal disease. In: British Journal of Clinical Pharmacology. 2008 ; Vol. 66, No. 5. pp. 717-722.
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abstract = "BACKGROUND: Haemodialysis (HD) is associated with the acute loss through the dialysis membrane of biochemical factors either enhancing [folic acid (F)] or impairing [asymmetric dimethylarginine (ADMA)] arterial function. Changes in these opposing factors might explain the absence of significant modifications in arterial function during HD. We speculated that intra-HD, instead of pre-HD, F administration would provide beneficial effects on arterial wave reflections and endothelial function by preventing HD-induced F loss. METHODS: Arterial wave reflections [augmentation index (AIx), pulse-wave analysis], endothelium-dependent vasodilation (salbutamol-mediated changes in AIx) and plasma concentrations of F and ADMA were measured pre-HD and end-HD in 10 patients (age 67.7 +/- 10.3 years). Each subject received F 5 mg either pre-HD or intra-HD in two separate studies 2-4 weeks apart, in an open-label randomized cross-over trial. RESULTS: Pre-HD F administration did not prevent significant reductions in F during HD (end-HD vs. pre-HD, -865 +/- 465 nmol l(-1), P <0.001), but no significant changes in AIx (+1.4 +/- 5.7{\%}) or salbutamol-mediated AIx modifications (+0.4 +/- 5.5{\%}) were observed. By contrast, intra-HD F administration was associated with significant increases in F (+298 +/- 283 nmol l(-1), P = 0.010) and a significant reduction of AIx (-4.7 +/- 7.2{\%}, P = 0.013), but no effects on salbutamol-mediated AIx changes (+1.5 +/- 4.4{\%}). There was a trend towards greater HD-induced reductions in plasma ADMA concentrations with intra-HD F administration (P = 0.066). CONCLUSIONS: Intra-HD F administration reduces arterial wave reflections but not endothelial function during HD. Given the prognostic significance of arterial wave reflections in HD patients, the timing of F administration is important in the design of interventional trials in this cohort.",
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T1 - Effects of pre- vs. intra-dialysis folic acid on arterial wave reflections and endothelial function in patients with end-stage renal disease

AU - Tochihara, Yuka

AU - Whiting, Malcolm J

AU - Barbara, Jeffrey A

AU - Mangoni, Arduino Aleksander

PY - 2008/11

Y1 - 2008/11

N2 - BACKGROUND: Haemodialysis (HD) is associated with the acute loss through the dialysis membrane of biochemical factors either enhancing [folic acid (F)] or impairing [asymmetric dimethylarginine (ADMA)] arterial function. Changes in these opposing factors might explain the absence of significant modifications in arterial function during HD. We speculated that intra-HD, instead of pre-HD, F administration would provide beneficial effects on arterial wave reflections and endothelial function by preventing HD-induced F loss. METHODS: Arterial wave reflections [augmentation index (AIx), pulse-wave analysis], endothelium-dependent vasodilation (salbutamol-mediated changes in AIx) and plasma concentrations of F and ADMA were measured pre-HD and end-HD in 10 patients (age 67.7 +/- 10.3 years). Each subject received F 5 mg either pre-HD or intra-HD in two separate studies 2-4 weeks apart, in an open-label randomized cross-over trial. RESULTS: Pre-HD F administration did not prevent significant reductions in F during HD (end-HD vs. pre-HD, -865 +/- 465 nmol l(-1), P <0.001), but no significant changes in AIx (+1.4 +/- 5.7%) or salbutamol-mediated AIx modifications (+0.4 +/- 5.5%) were observed. By contrast, intra-HD F administration was associated with significant increases in F (+298 +/- 283 nmol l(-1), P = 0.010) and a significant reduction of AIx (-4.7 +/- 7.2%, P = 0.013), but no effects on salbutamol-mediated AIx changes (+1.5 +/- 4.4%). There was a trend towards greater HD-induced reductions in plasma ADMA concentrations with intra-HD F administration (P = 0.066). CONCLUSIONS: Intra-HD F administration reduces arterial wave reflections but not endothelial function during HD. Given the prognostic significance of arterial wave reflections in HD patients, the timing of F administration is important in the design of interventional trials in this cohort.

AB - BACKGROUND: Haemodialysis (HD) is associated with the acute loss through the dialysis membrane of biochemical factors either enhancing [folic acid (F)] or impairing [asymmetric dimethylarginine (ADMA)] arterial function. Changes in these opposing factors might explain the absence of significant modifications in arterial function during HD. We speculated that intra-HD, instead of pre-HD, F administration would provide beneficial effects on arterial wave reflections and endothelial function by preventing HD-induced F loss. METHODS: Arterial wave reflections [augmentation index (AIx), pulse-wave analysis], endothelium-dependent vasodilation (salbutamol-mediated changes in AIx) and plasma concentrations of F and ADMA were measured pre-HD and end-HD in 10 patients (age 67.7 +/- 10.3 years). Each subject received F 5 mg either pre-HD or intra-HD in two separate studies 2-4 weeks apart, in an open-label randomized cross-over trial. RESULTS: Pre-HD F administration did not prevent significant reductions in F during HD (end-HD vs. pre-HD, -865 +/- 465 nmol l(-1), P <0.001), but no significant changes in AIx (+1.4 +/- 5.7%) or salbutamol-mediated AIx modifications (+0.4 +/- 5.5%) were observed. By contrast, intra-HD F administration was associated with significant increases in F (+298 +/- 283 nmol l(-1), P = 0.010) and a significant reduction of AIx (-4.7 +/- 7.2%, P = 0.013), but no effects on salbutamol-mediated AIx changes (+1.5 +/- 4.4%). There was a trend towards greater HD-induced reductions in plasma ADMA concentrations with intra-HD F administration (P = 0.066). CONCLUSIONS: Intra-HD F administration reduces arterial wave reflections but not endothelial function during HD. Given the prognostic significance of arterial wave reflections in HD patients, the timing of F administration is important in the design of interventional trials in this cohort.

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KW - albuterol

KW - arginine

KW - cross-over studies

KW - drug administration schedule

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KW - female

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KW - humans

KW - kidney failure, chronic

KW - male

KW - middle aged

KW - radial artery

KW - renal dialysis

KW - statistics, nonparametric

KW - vasodilator agents

KW - arterial wave reflection

KW - endothelial function

KW - haemodialysis

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