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Abstract: TH-PO939

Treatment of Anemia with Oral and Parenteral Iron Leads to Bone Loss in Juvenile Mice with CKD

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Akchurin, Oleh M., Weill Cornell Medicine, New York, New York, United States
  • Patino, Edwin, Weill Cornell Medicine, New York, New York, United States
  • Angara, Sureshbabu, Weill Cornell Medicine, New York, New York, United States
  • Bhatia, Divya, Weill Cornell Medicine, New York, New York, United States
  • Dalal, Vidhi, Weill Cornell Medicine, New York, New York, United States
  • Meza, Kelly, Weill Cornell Medicine, New York, New York, United States
  • Rivella, Stefano, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Choi, Mary E., Weill Cornell Medicine, New York, New York, United States
Background

Anemia is common in children with CKD and is associated with altered iron metabolism. Thus, many children with CKD are receiving iron therapy. Iron sequestration due to elevated hepcidin is a concern in CKD. Iron supplementation induces bone loss in mice without CKD. The effects of iron on bone health in juvenile CKD remain poorly understood.

Methods

CKD in juvenile mice was induced by 8 weeks of a 0.2% adenine diet, post-weaning. Bone histology and micro-CT was compared between four groups of mice:
1. Control (no CKD).
2. CKD without iron supplementation.
3. CKD + weekly 0.5g/kg of iron dextran intraperitoneally (CKD-IPFe).
4. CKD + 0.5% carbonyl iron diet (CKD-POFe).
ANOVA was used for statistical analysis. For all reported data, pairwise comparisons between groups 1/2, 2/3, and 2/4 were significant (p<0.05).

Results

Renal function was reduced in all CKD groups (serum creatinine 0.22, 0.55, 0.32, and 0.79 mg/dL in groups 1-4 respectively). As expected, mice with untreated CKD were anemic. Treatment with oral and IP iron resulted in improvement of Hgb (13.9, 11.5, 13.1, and 13.3 g/dL in groups 1-4), Hct, MCV, MCH, and RDW.
Mice with CKD had thinner and more porous cortical bone, and lower trabecular bone mass compared to controls. Iron treatment resulted in further cortical thinning (Ct.Th 0.18, 0.15, 0.12, 0.10 mm in groups 1-4), and decrease in cortical tissue mineral / apparent density, compared to untreated mice with CKD. Iron treatment also led to further reduction of trabecular bone volume (BV/TV 17.6, 12.2, 8.8, 8.6% in groups 1-4), trabecular number and increase in trabecular separation (Fig), compared to untreated mice with CKD.

Conclusion

Iron therapy improved anemia but was complicated by the loss of cortical and trabecular bone in this model of juvenile CKD. In our ongoing studies we aim to elucidate the underlying mechanisms. Our findings suggest a need to consider potential bone-related effects of iron in optimizing CKD management in children with CKD.

Cortical and trabecular bone micro-CT in four groups of mice