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Abstract: PO0458

Associations Between Hepcidin and Laboratory Measures of Iron and Inflammation in Patients with Anemia and CKD Not on Dialysis in the Roxadustat Global Phase 3 Program

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Fishbane, Steven, Zucker School of Medicine at Hofstra/Northwell Health, Great Neck, New York, United States
  • Provenzano, Robert, Wayne State University, Detroit, Michigan, 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 anemic patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) in the roxadustat studies.

Methods

This exploratory analysis used data from 3 similarly designed pivotal phase 3 studies (OLYMPUS, ANDES, and ALPS) of roxadustat vs. placebo in anemic patients with stage 3-5 NDD-CKD. Quintiles of baseline (BL) hepcidin levels and change 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

2717 patients were assessed (1630 roxadustat, 1087 placebo). BL hepcidin (range 0.75 to 808.2 μg/L) was analyzed by quintile regardless of treatment group. Patients with higher BL hepcidin were observed to have a lower hemoglobin (Hb), lower eGFR, higher C-reactive protein (CRP), higher serum iron, higher ferritin, lower total iron binding capacity (TIBC), and higher transferrin saturation (TSAT) compared to lower BL hepcidin groups (Table). 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(-), eGFR(-), albumin(+), Hb(-). The mean (SD) CFB in hepcidin at week 24 was -23.1 (86.0) μg/L in the roxadustat group vs. +12.3 (87.8) μg/L in the placebo group. Hepcidin associations after treatment will also be presented.

Conclusion

Baseline hepcidin was strongly associated with iron parameters like serum ferritin but not other known factors, such as CRP, in NDD-CKD patients with anemia.

Funding

  • Commercial Support