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

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.