Hemoglobin (HB) correction with roxadustat is associated with improved iron homeostasis in patients with dialysis-dependent CKD (DD-CKD)

Background: Anemia in CKD is multifactorial, with contributions from reduced erythropoietin production and hepcidin-induced functional iron deficiency. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, treats anemia by enhancing erythropoietin synthesis and increasing iron availability via reducing hepcidin and increasing iron transport. We assessed the effect of roxadustat on iron parameters in patients with DD-CKD. Methods: Patients were randomized to open label roxadustat or epoetin alfa in 3 pivotal DD-CKD trials. Intravenous (IV) iron was administered per usual care with epoetin alfa and was limited to rescue therapy with roxadustat. Mean changes from baseline in Hb, hepcidin, and iron parameters were evaluated. Pooled results are reported. Results: Overall, 3890 patients were evaluated (roxadustat N=1943; epoetin alfa N=1947; mean baseline Hb 9.7 g/dL for both groups), including 1515 incident dialysis patients (roxadustat N=756; epoetin alfa N=759; overall mean baseline Hb values ∼8.8 g/dL). Mean Hb increased more from baseline averaged over Weeks 28-52 with roxadustat vs epoetin alfa (1.21 vs 0.95 g/dL; P<0.0001). Roxadustat-treated patients used less IV iron, with mean monthly IV iron use over Weeks 28-52 of 80.3 mg for roxadustat and 108.2 mg for epoetin alfa (P<0.0001). Roxadustat reduced hepcidin and increased transferrin and serum iron; transferrin saturation did not change vs epoetin alfa (Figure). Reduction in ferritin occurred predominantly in patients with the highest baseline values when assessed by quartile (>800 μg/L). Conclusions: Roxadustat facilitated iron transport and utilization by increasing both iron-carrying capacity (transferrin) and serum iron, in contrast to the effects on these parameters seen with epoetin alfa. Overall, these changes contributed to decreased need for IV iron use while achieving greater Hb increase from baseline with roxadustat vs epoetin alfa. (Figure Presented).