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Effects of Daprodustat on Iron Metabolism in Peritoneal Dialysis Patients: An Exploratory Study
Tomohiro Yan1, Yukinao Sakai2, Shunnosuke Kunoki1
1Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Introduction:
Renal anemia is a serious complication in patients with chronic kidney disease. Daprodustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, represents a potential therapeutic option for renal anemia; however, its efficacy and safety in patients maintained on peritoneal dialysis (PD) remain unknown. This exploratory study aimed to evaluate the preliminary effects of daprodustat in patients with chronic kidney disease undergoing maintenance PD.
Methods:
This single-center, prospective study included 11 patients undergoing maintenance PD who shifted from darbepoetin alfa to daprodustat. Over a 24-week observation period, hematological parameters, iron metabolism markers, cardiac function, and oxidative stress indicators were monitored. Statistical significance was determined using repeated-measures ANOVA with Bonferroni correction for multiple comparisons.
Results:
Hepcidin-25 levels (p = 0.0004) and oxidized low-density lipoprotein levels (p = 0.0437) significantly decreased, while total iron-binding capacity (p = 0.0043) and reticulocyte counts (p = 0.0052) significantly increased. Despite these favorable biochemical changes, hemoglobin and hematocrit values showed no significant improvement. Other oxidative stress markers showed downward trends, while cardiac function parameters (N-terminal pro-brain natriuretic peptide, cardiothoracic ratio, left ventricular ejection fraction) remained unchanged.
Conclusion:
This pilot study suggests that daprodustat may enhance iron metabolism and mitigate oxidative stress while preserving cardiac function in PD patients. The pronounced reduction in hepcidin-25 levels indicates potential beneficial effects on iron homeostasis. However, the absence of significant hemoglobin improvement, combined with the small sample size (n = 11), lack of control group, and short 24-week follow-up period, significantly limits the clinical relevance and generalizability of these findings. Larger randomized controlled trials with longer follow-up periods are essential to definitively establish the efficacy and safety of daprodustat in this patient population.
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