Publicação
Evolution of Circulating Bone-Related Biomarkers After Kidney Transplantation
| Resumo: | Aim: Bone disease after kidney transplant (KT) results from multiple factors, including previous bone and mineral metabolism disturbances and effects from transplant-related medications. New biomolecules have been recently associated with the development and progression of the chronic kidney disease-associated bone and mineral disorder (CKD-MBD). These include sclerostin and the soluble receptor activator of nuclear factor-kB ligand (sRANKL). Methods: To better understand the role of new biomarkers in post-transplant bone disease, this study was designed to prospectively evaluate and correlate results from the histomorphometric analysis of bone biopsies after KT with emerging serum biomarkers of the CKD-MBD: sclerostin, Dickkopf-related protein 1 (Dkk-1), sRANKL and osteoprotegerin (OPG). Results: Our data shows a significant increase in plasma levels of bioactive sclerostin after KT accompanied by a significant reduction in plasma levels of Dkk-1, suggesting a promotion of the inhibition of bone formation by osteoblasts through the activation of these inhibitors of the Wnt signaling pathway. In addition, we found a significant increase in plasma levels of free sRANKL after KT accompanied by a significant reduction in plasma levels of its decoy receptor OPG, suggesting an enhanced bone reabsorption by osteoclasts mediated by this mechanism. Conclusions: Taken together, these results suggest that the loss of bone volume observed after KT could be related mainly with the inhibition of bone formation mediated by sclerostin accompanied by an enhanced bone reabsorption mediated by sRANKL. |
|---|---|
| Autores principais: | Juliana Carvalho Magalhães |
| Assunto: | Medicina clínica Clinical medicine |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Porto |
| Idioma: | português |
| Origem: | Repositório Aberto da Universidade do Porto |
| Resumo: | Aim: Bone disease after kidney transplant (KT) results from multiple factors, including previous bone and mineral metabolism disturbances and effects from transplant-related medications. New biomolecules have been recently associated with the development and progression of the chronic kidney disease-associated bone and mineral disorder (CKD-MBD). These include sclerostin and the soluble receptor activator of nuclear factor-kB ligand (sRANKL). Methods: To better understand the role of new biomarkers in post-transplant bone disease, this study was designed to prospectively evaluate and correlate results from the histomorphometric analysis of bone biopsies after KT with emerging serum biomarkers of the CKD-MBD: sclerostin, Dickkopf-related protein 1 (Dkk-1), sRANKL and osteoprotegerin (OPG). Results: Our data shows a significant increase in plasma levels of bioactive sclerostin after KT accompanied by a significant reduction in plasma levels of Dkk-1, suggesting a promotion of the inhibition of bone formation by osteoblasts through the activation of these inhibitors of the Wnt signaling pathway. In addition, we found a significant increase in plasma levels of free sRANKL after KT accompanied by a significant reduction in plasma levels of its decoy receptor OPG, suggesting an enhanced bone reabsorption by osteoclasts mediated by this mechanism. Conclusions: Taken together, these results suggest that the loss of bone volume observed after KT could be related mainly with the inhibition of bone formation mediated by sclerostin accompanied by an enhanced bone reabsorption mediated by sRANKL. |
|---|