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Kidney Week

Abstract: PO0459

Associations Between Hepcidin and Laboratory Measures of Iron and Inflammation in Incident Dialysis Patients with Anemia Enrolled in the Roxadustat Global Phase 3 Program

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Provenzano, Robert, Wayne State University, Detroit, Michigan, United States
  • Fishbane, Steven, Zucker School of Medicine at Hofstra/Northwell Health, Great Neck, New York, United States
  • Liu, Cameron S., FibroGen, Inc., San Francisco, California, United States
  • Lee, Tyson T., FibroGen, Inc., San Francisco, California, United States
  • Saikali, Khalil Georges, FibroGen, Inc., San Francisco, California, United States
  • Szczech, Lynda, FibroGen, Inc., San Francisco, California, United States
Background

Hepcidin is the master regulator of iron homeostasis. Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates coordinated erythropoiesis in part by reducing hepcidin. We investigated the associations between hepcidin levels and select laboratories in incident dialysis (ID) patients with anemia.

Methods

This exploratory analysis used data from three similarly designed, pivotal, phase 3 studies (ROCKIES, HIMALAYAS, and SIERRAS) of roxadustat vs. epoetin alfa in anemic patients with dialysis-dependent chronic kidney disease (CKD). Patients on dialysis for 2 weeks to ≤4 months prior to randomization (defined as ID) were included in the analysis. Quintiles of baseline (BL) hepcidin levels and changes from baseline (CFB) in hepcidin were evaluated for associations with select labs at BL and changes at weeks 20-28. Multivariate regression to hepcidin was performed at BL and after treatment using full analysis set.

Results

1297 ID patients were assessed (646 roxadustat, 651 epoetin alfa). BL hepcidin (range 5 to 1118.7 μg/L) was analyzed by quintile regardless of treatment arm. Patients with higher BL hepcidin were observed to have higher C-reactive protein (CRP), higher serum iron, higher ferritin, lower total iron binding capacity (TIBC), and higher transferrin saturation (TSAT) compared to lower hepcidin groups (Table 1). Further analysis of these relationships using multivariate regression models with minimalized AIC score model selection criteria showed that BL hepcidin (log-transformed) was significantly associated with the following BL parameters(log-transformed) in the descending order of importance (+/- indicated the direction): ferritin(+), TIBC(-), albumin(+), CRP(+), iron(+). The mean (SD) CFB to week 24 in hepcidin was -63.47 (121.8) μg/L in the roxadustat group vs. -34.84 (141.6) μg/L in the epoetin group. Hepcidin associations after treatment will also be included in the presentation.

Conclusion

Baseline hepcidin was strongly associated with baseline iron parameters and CRP in ID patients with anemia of CKD.

Funding

  • Commercial Support