BACKGROUND: Pentoxifylline has been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin-stimulating agent (ESA)-hyporesponsive anaemia in the Handling Erythropoietin Resistance with Oxpentifylline (HERO) multi-centre double-blind, randomized controlled trial. The present sub-study evaluated the effects of pentoxifylline on the iron-regulatory hormone hepcidin in ESA-hyporesponsive CKD patients. METHODS: This sub-study included 13 patients in the pentoxifylline arm (400 mg daily) and 13 in the matched placebo arm. Hepcidin-25 was measured by Ultra Performance Liquid Chromatography/Quadrupole time-of-flight mass spectrometry following isolation from patient serum. Serum hepcidin-25, serum iron biomarkers, haemoglobin and ESA dosage were compared within and between the two groups. RESULTS: Hepcidin-25 concentration at 4 months adjusted for baseline did not differ significantly in pentoxifylline vs. placebo treated patients (adjusted mean difference (MD) -7.9 nmol, P = 0.114), although the difference between the groups mean translated into a >25% reduction of circulating hepcidin-25 due to pentoxifylline compared to the placebo baseline. In paired analysis serum hepcidin-25 levels were significantly decreased at 4 months compared to baseline in the pentoxifylline group (-5.47 +/- 2.27 nmol/l, P < 0.05), but not in the placebo group (2.82 +/- 4.29 nmol/l, P = 0.24). Pentoxifylline did not significantly alter serum ferritin (MD 55.4mcg/l), transferrin saturation (MD 4.04%), the dosage of ESA (MD -9.93 U/kg/week), or haemoglobin concentration (MD 5.75 g/l). CONCLUSIONS: The reduction of circulating hepcidin-25 due to pentoxifylline did not reach statistical significance, however, the magnitude of the difference suggests that pentoxifylline may be a clinically and biologically meaningful modulator of hepcidin-25 in dialysis patients with ESA-hyporesponsive anaemia.
AD - Separation Science & Metabolomics Laboratory and Metabolomics Australia, Murdoch University Node, Perth, Australia.BACKGROUND: Pentoxifylline has been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin-stimulating agent (ESA)-hyporesponsive anaemia in the Handling Erythropoietin Resistance with Oxpentifylline (HERO) multi-centre double-blind, randomized controlled trial. The present sub-study evaluated the effects of pentoxifylline on the iron-regulatory hormone hepcidin in ESA-hyporesponsive CKD patients. METHODS: This sub-study included 13 patients in the pentoxifylline arm (400 mg daily) and 13 in the matched placebo arm. Hepcidin-25 was measured by Ultra Performance Liquid Chromatography/Quadrupole time-of-flight mass spectrometry following isolation from patient serum. Serum hepcidin-25, serum iron biomarkers, haemoglobin and ESA dosage were compared within and between the two groups. RESULTS: Hepcidin-25 concentration at 4 months adjusted for baseline did not differ significantly in pentoxifylline vs. placebo treated patients (adjusted mean difference (MD) -7.9 nmol, P = 0.114), although the difference between the groups mean translated into a >25% reduction of circulating hepcidin-25 due to pentoxifylline compared to the placebo baseline. In paired analysis serum hepcidin-25 levels were significantly decreased at 4 months compared to baseline in the pentoxifylline group (-5.47 +/- 2.27 nmol/l, P < 0.05), but not in the placebo group (2.82 +/- 4.29 nmol/l, P = 0.24). Pentoxifylline did not significantly alter serum ferritin (MD 55.4mcg/l), transferrin saturation (MD 4.04%), the dosage of ESA (MD -9.93 U/kg/week), or haemoglobin concentration (MD 5.75 g/l). CONCLUSIONS: The reduction of circulating hepcidin-25 due to pentoxifylline did not reach statistical significance, however, the magnitude of the difference suggests that pentoxifylline may be a clinically and biologically meaningful modulator of hepcidin-25 in dialysis patients with ESA-hyporesponsive anaemia.
PY - 2016 SN - 1440-1797 (Electronic)