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The Role of Bone Volume, FGF23 and Sclerostin in Calcifications and Mortality; a Cohort Study in CKD Stage 5 Patients

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Abstract

Chronic kidney disease-mineral and bone disorder has been associated with increasing morbid-mortality. The aim of this study was to determine the prevalence and phenotype of bone disease before transplantation and to correlate FGF23 and sclerostin levels with bone histomorphometry, and study possible associations between FGF23, sclerostin, and bone histomorphometry with cardiovascular disease and mortality. We performed a cross-sectional cohort study of a sample of 84 patients submitted to renal transplant, which were prospectively followed for 12 months. Demographic, clinical, and echocardiographic data were collected, laboratory evaluation, bone biopsy, and X-ray of the pelvis and hands were performed. Patient and graft survival were recorded. We diagnosed low bone turnover in 16 patients (19.5%); high bone turnover in 22 patients (26.8%); osteomalacia in 1 patient (1.2%), and mixed renal osteodystrophy in 3 patients (3.7%). At the end of 12 months, 5 patients had graft failure (5.9%), 4 had a cardiovascular event (4.8%), and 4 died. Age was associated with low remodeling disease, whereas high BALP and phosphorus and low sclerostin with high turnover disease. Sclerostin was a risk factor for isolated low bone volume. High BALP, low phosphorus, and low FGF23 were risk factors for abnormal mineralization. FGF23 appears as an independent factor for severity of vascular calcifications and for cardiovascular events, whereas the presence of valve calcifications was associated with low volume and with turnover deviations. Sclerostin was associated a higher HR for death. Sclerostin and FGF23 seemed to provide higher cardiovascular risk, as well as low bone volume, which associated with extra-osseous calcifications.

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Data Availability

The data that support the findings of this study are available upon reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

We thank CHULC, the institution where the study was conducted. We thank the Portuguese Society of Nephrology and the Portuguese Society of Transplantation/Astellas for awarding us a research grant. We would like to thank Sandra Silva for helping with administrative work and to Dr Isabel Mesquita for helping with sample storage. We also thank the surgeons Ana Pena and Sofia Carrelha and all the operating room staff for being available to help us with the bone biopsies performed in the operating room.

Funding

A grant from the Portuguese Society of Nephrology. A grant from the Portuguese Society of Transplantation/Astellas.

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Authors and Affiliations

  1. Nephrology Department, Hospital Curry Cabral|CHULC, Rua da Beneficência nº8, 1050-099, Lisbon, Portugal

    Ana Carina Ferreira, Patrícia Cotovio, Inês Aires, Marco Mendes, David Navarro, Cecília Silva, Fernando Caeiro, Fernando Nolasco & Aníbal Ferreira

  2. Nova Medical School, Lisbon, Portugal

    Ana Carina Ferreira, Inês Aires, Fernando Nolasco & Aníbal Ferreira

  3. CEDOC, Tissue Repair and Inflammation Lab, Lisbon, Portugal

    Rute Salvador, Bruna Correia & Guadalupe Cabral

Authors
  1. Ana Carina Ferreira
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  2. Patrícia Cotovio
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  3. Inês Aires
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  4. Marco Mendes
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  5. David Navarro
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  10. Guadalupe Cabral
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  11. Fernando Nolasco
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  12. Aníbal Ferreira
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Contributions

ACF and AF concept and design the study; ACF, PC, IA, MM, DN, CS, FC, RS, BC, and GC collected data or perform bone biopsies or performed laboratory evaluations; ACF, MM, RS, BC, GC, FN, AF analyzed the data; ACF drafted the article; PC, IA, MM, DN, CS, FC, RS, BC, GC, FN, AF revised the paper; all authors approved the final version of the paper and agree with all aspects of the work.

Corresponding author

Correspondence to Ana Carina Ferreira.

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Conflict of interest

Besides receiving a grant from the Portuguese Society of Nephrology and the Portuguese Society of Transplantation/Astellas, we do not have any conflict of interest relating with this manuscript. The results presented in this paper have not been published previously in whole or part, except in abstract format.

Human and Animal Rights and Informed Consent

The institutions’ local ethics committees approved this study. Written consent was obtained from all participants prior to entering the protocol.

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Ferreira, A.C., Cotovio, P., Aires, I. et al. The Role of Bone Volume, FGF23 and Sclerostin in Calcifications and Mortality; a Cohort Study in CKD Stage 5 Patients. Calcif Tissue Int 110, 215–224 (2022). https://doi.org/10.1007/s00223-021-00910-8

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  • DOI: https://doi.org/10.1007/s00223-021-00910-8

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