Joel Gummer1, Robert Trengove1, Elaine M Pascoe2, Sunil V Badve2,3, Alan Cass2,4, Philip Clarke5, Stephen P McDonald6, Alicia T Morrish2, Eugenie Pedagogos7, Vlado Perkovic2,8, Donna Reidlinger2, Anish Scaria2, Rowan Walker9, Liza A Vergara2, Carmel M Hawley2,10, David W Johnson2,10, John K Olynyk11,12,13, Paolo Ferrari14,15. 1. Separation Science and Metabolomics Laboratory and Metabolomics Australia, Murdoch University Node, Perth, Australia. 2. Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia. 3. Department of Nephrology, St George Hospital, Sydney, Australia. 4. Menzies School of Health Research, Darwin, Australia. 5. Centre for Health Policy, Programs and Economics, University of Melbourne, Melbourne, Australia. 6. Department of Nephrology and Transplantation Services, University of Adelaide at Central Northern Adelaide Renal and Transplantation Services, Adelaide, Australia. 7. Department of Nephrology, Royal Melbourne Hospital, Melbourne, Australia. 8. The George Institute for Global Health, Sydney, Australia. 9. Department of Renal Medicine, The Alfred Hospital, Melbourne, Australia. 10. Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia. 11. Department of Gastroenterology, Fremantle and Fiona Stanley Hospitals, Perth, Australia. 12. School of Veterinary Sciences, Murdoch University, Perth, Australia. 13. School of Biomedical Sciences and Curtin Health Innovation Research Institute, Curtin University, Perth, Australia. 14. Department of Nephrology, Prince of Wales Hospital, Sydney, Australia. 15. Clinical School, University of New South Wales, Sydney, Australia.
Abstract
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 multicentre double-blind, randomized controlled trial. The present sub-study evaluated the effects of pentoxifylline on the iron-regulatory hormone hepcidin in patients with ESA-hyporesponsive CKD. METHODS: This sub-study included 13 patients in thepentoxifyllinearm (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 versus 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 with the placebo baseline. In paired analysis, serum hepcidin-25 levels were significantly decreased at 4 months compared with 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 55.4 mcg/l), transferrin saturation (MD 4.04%), the dosage of ESA (MD -9.93 U/kg per week) or haemoglobin concentration (MD 5.75 g/l). CONCLUSION: 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 of patients with ESA-hyporesponsive anaemia.
RCT Entities:
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 multicentre double-blind, randomized controlled trial. The present sub-study evaluated the effects of pentoxifylline on the iron-regulatory hormone hepcidin in patients with ESA-hyporesponsive CKD. 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 versus 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 with the placebo baseline. In paired analysis, serum hepcidin-25 levels were significantly decreased at 4 months compared with 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 55.4 mcg/l), transferrin saturation (MD 4.04%), the dosage of ESA (MD -9.93 U/kg per week) or haemoglobin concentration (MD 5.75 g/l). CONCLUSION: 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 of patients with ESA-hyporesponsive anaemia.
Authors: Laurence Britton; Kim Bridle; Janske Reiling; Nishreen Santrampurwala; Leesa Wockner; Helena Ching; Katherine Stuart; V Nathan Subramaniam; Gary Jeffrey; Tim St Pierre; Michael House; Joel Gummer; Robert Trengove; John Olynyk; Darrell Crawford; Leon Adams Journal: Hepatol Commun Date: 2018-04-27
Authors: Edward Litton; Stuart Baker; Wendy Erber; Shannon Farmer; Janet Ferrier; Craig French; Joel Gummer; David Hawkins; Alisa Higgins; Axel Hofmann; Bart De Keulenaer; Julie McMorrow; John K Olynyk; Toby Richards; Simon Towler; Robert Trengove; Steve Webb Journal: J Intensive Care Date: 2018-09-10
Authors: Martin K Mead; Melissa Claus; Edward Litton; Lisa Smart; Anthea Raisis; Gabriele Rossi; Robert D Trengove; Joel P A Gummer Journal: Sci Rep Date: 2019-12-18 Impact factor: 4.379
Authors: Reece Jefferies; Harish Puttagunta; Anoushka Krishnan; Ashley Irish; Ramyasuda Swaminathan; John K Olynyk Journal: Front Med (Lausanne) Date: 2022-02-22