Could Bone Biomarkers Predict Bone Turnover after Kidney Transplantation?-A Proof-of-Concept Study

Autores da FMUP

• Janete Maria Quelhas Dos Santos

  Autor

• Ricardo Morais Pereira Neto

  Autor

• João Miguel Machado Dória Frazão

  Autor

Participantes de fora da FMUP

• Magalhaes, J
• Pereira, L
• Castro Ferreira, I
• Martins, S
• Carvalho, C

Unidades de investigação

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Medicina

• Recursos Comuns

  

  Investigador

  Guilhermina Maria Da Silva Rêgo

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Aim: Bone disease after kidney transplant (KT) results from multiple factors, including previous bone and mineral metabolism disturbances and effects of 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 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 osteo-protegerin (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 resorption by osteoclasts mediated by this mechanism. Conclusions: Taken together, these results suggest that the loss of bone volume observed after KT could be explain mainly by the inhibition of bone formation mediated by sclerostin accompanied by an enhanced bone resorption mediated by sRANKL.

Keywords

• bone biomarkers; kidney transplantation; bone turnover