Kidney Week

Abstract: SA-PO238

Impact of Phosphate Binders on Bone Protein Expression in Rats Fed Diets with Different Phosphorus Concentrations

Session Information

• CKD-MBD: Basic and Translational
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 501 Bone and Mineral Metabolism: Basic

Authors

• Truyts, Tânia Priante de Oliveira Madid, Laboratório de Fisiopatologia Renal , Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Sao Paulo, Brazil

Tânia Priante de Oliveira Madid Truyts

• Ferreira, Juliana Cunha, Laboratório de Fisiopatologia Renal , Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Sao Paulo, Brazil

Juliana Cunha Ferreira, MD

• Neves, Katia R., Laboratório de Fisiopatologia Renal , Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Sao Paulo, Brazil

Katia R. Neves, MD, PhD

• Dominguez, Wagner, Laboratório de Fisiopatologia Renal , Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Sao Paulo, Brazil

Wagner Dominguez, MBChB

• Elias, Rosilene M., Laboratório de Fisiopatologia Renal , Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Sao Paulo, Brazil

Rosilene M. Elias, MD, PhD

• Jorgetti, Vanda, Laboratório de Fisiopatologia Renal , Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Sao Paulo, Brazil

Vanda Jorgetti, MD, PhD

• Moyses, Rosa M.A., Laboratório de Fisiopatologia Renal , Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Sao Paulo, Brazil

Rosa M.A. Moyses, MD, PhD

• dos Reis, Luciene, Laboratório de Fisiopatologia Renal , Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Sao Paulo, Brazil

Luciene dos Reis, PhD

Background

Managing hyperphosphatemia is important in treating chronic kidney disease (CKD) to prevent bone and cardiovascular complications. Phosphate (P) binders play a key role in this control. This study evaluated the efficacy of calcium carbonate (CaCO3) and sevelamer carbonate (Sev) on the bone expression of proteins involved in the Wnt/β-catenin pathway in nephrectomized (Nx) and parathyroidectomized (PTx) rats fed normal and high P diets.

Methods

Wistar rats underwent 5/6 nephrectomy (Nx), parathyroidectomy (PTx), and were fed diets with different P concentrations (0.6% and 1.2%). The animals were divided according to diet and treatment with the binders. Biochemical analyses were performed on all animals. Bone expression of sclerostin, DKK1, and β-catenin was evaluated using mRNA levels and immunohistochemistry (IH), whereas FGF23 was evaluated only by IH. Statistical analysis using the General Linear Model was applied to study the effects of diet and treatment in these animals.

Results

Table 1 describes the interaction between different P concentrations in the diet and the effects of both treatments on biochemical analysis, IH expression, and mRNA levels. Post-test analysis disclosed that serum P, fractional P excretion and ionized calcium (Cai) were influenced by both the different diets and the two binders, as well as osteocytic expression of sclerostin and FGF23, and mRNA levels of SOST.

Conclusion

Our results showed that treatment with both binders was effective in decreasing serum P and fractional excretion and increasing Cai. Phosphate overload increased FGF23 expression in the bone, and both binders were effective in reducing this expression. The Wnt/β-catenin pathway was blocked by sclerostin, with higher expression in animals with P overload, and both treatments reduced its expression, which was also observed in gene expression. These results demonstrated that P overload can inhibit the Wnt/β-catenin pathway and that both binders effectively reversed phosphate's effects.

Table 1.