Roxadustat beneficial for improving iron metabolism in peritoneal dialysis patients

The study, published in the European Journal of Medical Research, found that compared with the ESA group, the roxadustat group showed significant differences in all iron biomarker levels except transferrin saturation (TSAT) and serum ferritin (sFt).

Erythropoiesis-stimulating agents received first approval in 1989, since then, the class have ascended to a role as a standard of care for anaemia in patients with chronic kidney disease (CKD). ESAs have become a staple in anaemia management in CKD, however, their use is associated with an increased risk of iron metabolism disorders. This, along with other factors has led to the development of the oral hypoxia-inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) class and agents such as roxadustat and daprodustat (Jesduvroq), which received approval from the US FDA (Food and Drug Administration) for anaemia treatment in patients with CKD who are on dialysis in February 2023.

Roxadustat boasts approvals from regulatory agencies in China, Japan, the European Union, and other countries for anaemia treatment of CKD in adult patients on dialysis and not on dialysis, despite not receiving approval in the US. There is a need for more data to demonstrate roxadustat's efficacy in regulating iron metabolism in patients with peritoneal dialysis compared with erythropoiesis-stimulating agents.

To fill this knowledge gap, Dong Sun, Department of Internal Medicine and Diagnostics, Xuzhou Medical University, Xuzhou, China, and colleagues report the results of a 24-week, cohort study involving patients with peritoneal dialysis to analyze the effect of roxadustat on iron metabolism by comparing changes in iron biomarker levels including serum soluble transferrin receptor (sTFR).

This prospective cohort study included PD patients with a mean haemoglobin level of 60–100 g/L. The patients were randomized in the ratio of 2:1 to two groups: the roxadustat group (106 cases), and the ESA group (53 cases). The study's primary endpoint was the change in the iron biomarker levels and the proportion of patients with functional iron deficiency and absolute iron deficiency.

Based on the study, the researchers reported the following findings:

· Compared with ESAs, roxadustat significantly decreased hepcidin level (difference, − 20.09 ng/mL), attenuated the increase in serum sTFR level (difference, − 7.87 nmol/L), and reduced the proportion of patients with functional iron deficiency (roxadustat, 11.43%; ESA, 33.33%).

· There was no significant difference in the safety of the two groups throughout the study.

The 24-week prospective cohort study showed the benefit of roxadustat in improving iron metabolism in PD patients. In addition to its inhibitory effect on hepcidin, roxadustat was also shown to induce the expression of molecules required for iron circulation. Thus, the increased iron consumption seen in the roxadustat group may be not only due to enhanced hematopoietic production but also to improved iron utilization efficiency.

"Appropriate treatment options for PD could be selected by using information on the differences in the effects of roxadustat and ESAs on iron metabolism," the researchers wrote. "Roxadustat showed a manageable safety with no increased risk of the incidence of metabolic acidosis, hyperkalemia, and peritonitis."

Reference:

Zhang, X., Jia, R., Zheng, Z. et al. Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study. Eur J Med Res 28, 489 (2023). https://doi.org/10.1186/s40001-023-01465-0