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Kidney Week

Abstract: PO0317

Comparison of the Effects of Ferric Citrate and Intravenous Iron on Markers of Mineral and Bone Disorder and Oxidative Stress in a Rat Model of CKD-MBD

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Biruete, Annabel, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Chen, Neal X., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Metzger, Corinne E., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Stacy, Alexander James, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Srinivasan, Shruthi, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • O'Neill, Kalisha, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Dominguez, James M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Avin, Keith G., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Allen, Matthew R., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD) are common in CKD. Ferric citrate is an oral therapy approved as an oral iron replacement product in non-dialysis dependent CKD and as a phosphate binder for dialysis-dependent CKD patients. However, studies comparing the effects of ferric citrate vs. IV iron on markers of CKD-MBD and oxidative stress in moderate CKD are limited.

Methods

We compared four groups of male rats (n=11-14 rats/group): 1) Rats with normal kidney function (NL), 2) CKD rats without iron treatment (CKD), 3) CKD rats treated with 2% ferric citrate in food (CKD + FC), and 4) CKD rats treated with 1mg/kg/every other week of iron sucrose (CKD + IV iron). Treatments started at 18 weeks of age (mild CKD) until euthanized at 28 weeks of age (moderate-to-advanced CKD). We determined biochemical markers of CKD-MBD, oxidative stress, bone morphology (by CT), and bone formation rate at 28 weeks. One-way ANOVA was performed with Tukey’s post hoc comparisons.

Results

Untreated and iron-treated CKD rats had higher concentrations of BUN and creatinine than NL rats. Untreated CKD rats had elevated plasma phosphorus and intact FGF23 compared to NL. CKD+FC rats had lower plasma phosphorus and intact FGF23, while CKD+IV iron rats had lower intact FGF23 compared to CKD rats. However, the C-terminal FGF23 remained high in the untreated CKD and the CKD+IV iron rats compared to NL, but CKD+FC rats tended to be lower than the untreated CKD rats (p=0.07). PTH was elevated in the untreated and iron-treated CKD rats compared to NL. A marker of oxidative stress, 8OHdG, was increased in the untreated and iron-treated CKD rats compared to NL rats and was not different between iron treatments. At this stage of CKD, there was no cortical porosity in all the CKD rats compared to NL. CKD-induced alterations in trabecular and cortical bone properties and bone formation rate were not changed compared to untreated CKD rats in the iron-treated rats.

Conclusion

Ferric citrate led to more robust reductions in plasma phosphorus and FGF23 than IV iron, while neither source of iron had adverse effects on oxidative stress or bone parameters in a rat model with moderate CKD-MBD.

Funding

  • Other NIH Support