Association between serum hepcidin‐25 and primary resistance to erythropoiesis‐stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial

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