Effect of pentoxifylline on hepcidin and iron profile in hemodialysis patients: A randomized, double-blind, placebo-controlled clinical trial

Background: Hemodialysis (HD) patients often have elevated levels of hepcidin hormone, which is a key regulator of systemic iron homeostasis. While pentoxifylline (PTX) has been demonstrated to have anti-inflammatory properties, it is unclear if these effects would also have an inhibitory effect on hepcidin. This study aimed to examine the potential role of PTX on hepcidin and its consequent effects on iron profile and anemia in HD patients.

Methods: Eighty HD patients were randomly assigned 1:1 to the pentoxifylline group, receiving a daily dose of PTX (800mg), or the placebo group, receiving placebo capsules for 6-months. Different laboratory parameters, including hepcidin, hemoglobin (Hb), red blood cells (RBCs), hypoxia-inducible factor-2 alpha (HIF-2α), serum iron, total iron-binding capacity (TIBC), ferritin, transferrin saturation (TSAT), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs.CRP), were used for evaluation the patients' response.

Results: In the PTX-treated patients, the hepcidin levels reduced significantly (p=0.001) from 628.03 (334.4-800.85)ng/ml to 235.25 (192.8-508.76)ng/ml, and this reduction was also statistically significant as compared to the placebo group (p<0.001). Also, there were significant changes (p<0.001) regarding other iron hemostasis parameters including Hb, RBCs, serum iron, TIBC, TSAT, and HIF-2α. Levels of IL-6 and hs.CRP, as a reflection of inflammatory status, decreased significantly (p=0.002 and p=0.003, respectively) in the pentoxifylline group, and the percent reduction in these parameters was also statistically significant compared to the placebo group (p<0.001).

Conclusions: This study reveals that PTX reduces hepcidin levels and consequently provides an improvement in the iron profile and anemia in HD patients.