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Biochemical Clusters as Substitutes of Bone Biopsies in Kidney Transplant Patients

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Abstract

Bone and mineral metabolism abnormalities are frequent in kidney transplant recipients and have been associated with cardiovascular morbidity. The primary aim of this study was to analyse the association between routine clinically available biochemical evaluation, non-routine histomorphometric bone evaluation, and vascular disease in kidney transplanted patients. A cross-sectional analysis was performed on 69 patients, 1-year after kidney transplantation. Laboratory analysis, radiography of hands and pelvis, bone biopsy, bone densitometry, and coronary CT were performed. One-year post-transplantation, nearly one-third of the patients presented with hypercalcemia, 16% had hypophosphatemia, 39.3% had iPTH levels > 150 pg/mL, 20.3% had BALP levels > 40 U/L, and 26.1% had hypovitaminosis D. Evaluation of extraosseous calcifications revealed low Adragão and Agatston scores. We divided patients into three clusters, according to laboratory results routinely used in clinical practice: hypercalcemia and hyperparathyroidism (Cluster1); hypercalcemia and high BALP levels (Cluster2); hypophosphatemia and vitamin D deficiency (Cluster 3). Patients in clusters 1 and 2 had higher cortical porosity (p = 0.001) and osteoid measurements, although there was no difference in the presence of abnormal mineralization, or low volume. Patients in cluster 2 had a higher BFR/BS (half of the patients in cluster 2 had high bone turnover), and most patients in cluster 1 had low or normal bone turnover. Cluster 3 has no differences in volume, or turnover, but 60% of the patients presented with pre-osteomalacia. All three clusters were associated with high vascular calcifications scores. Vascular calcifications scores were not related to higher bone mineral density. Instead, an association was found between a higher Adragão score and the presence of osteoporosis at the femoral neck (p = 0.008). In conclusion, inferring bone TMV by daily clinical biochemical analysis can be misleading, and bone biopsy is important for assessing both bone turnover and mineralization after kidney transplantation, although hypophosphatemia combined with vitamin D deficiency is associated with abnormal mineralization. The presence of hypercalcemia with high levels of PTH or high levels of BALP, or hypophosphatemia and vitamin D deficiency should remind us to screen vascular calcification status of patients.

Clinical Research: ClinicalTrials.gov ID NCT02751099.

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Data Availability

The results presented in this paper have not been published previously in whole or part, except in the abstract format. The data supporting the findings of this study are available upon reasonable request from the corresponding author. The data were not publicly available because of privacy or ethical restrictions.

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Acknowledgements

We thank CHULC for their assistance with this study. We thank the Portuguese Society of Nephrology and Portuguese Society of Transplantation/Astellas for awarding us a research grant. We would like to thank Sandra Silva for help with administrative work, and Dr. Isabel Mesquita for help with sample storage and handling. We thank the Radiology Department of Hospital Santa Marta and Hospital Santo António dos Capuchos from CHULC for performing the CT scans and DXA examinations, respectively. We thank the patients for their consent to participate in this study.

Funding

This study was supported by a grant from the Portuguese Society of Nephrology and 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, Marco Mendes, Cecília Silva, Patrícia Cotovio, Inês Aires, David Navarro, Fernando Caeiro, Rute Salvador, Bruna Correia, Guadalupe Cabral, Fernando Nolasco & Aníbal Ferreira

  2. Nova Medical School, Lisbon, Portugal

    Ana Carina Ferreira, Marco Mendes, Inês Aires, Fernando Caeiro, Rute Salvador, Bruna Correia, Guadalupe Cabral, Fernando Nolasco & Aníbal Ferreira

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  1. Ana Carina Ferreira
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Contributions

ACF and AF: conceptualized and designed the study. ACF, MM, CS, PC, IA, DN, FC, RS, BC, and GC: collected data or performed bone biopsies or laboratory evaluations. ACF, MM, RS, BC, GC, FN, and AF: analyzed the data. ACF: drafted the article. MM, CS, PC, IA, DN, FC, RS, BC, GC, FN, and AF: revised the paper. All authors approved the final version of the paper and agreed 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 Portuguese Society of Transplantation/Astellas. Ana Carina Ferreira, Marco Mendes, Cecília Silva, Patrícia Cotovio, Inês Aires, David Navarro, Fernando Caeiro, Rute Salvador, Bruna Correia, Guadalupe Cabral, Fernando Nolasco and Aníbal Ferreira have no conflicts of interest related to the present manuscript.

Human and Animal Rights and Informed Consent

The study was approved by the Institutional Local Ethics Committee and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all patients at inclusion.

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Ferreira, A.C., Mendes, M., Silva, C. et al. Biochemical Clusters as Substitutes of Bone Biopsies in Kidney Transplant Patients. Calcif Tissue Int 114, 267–275 (2024). https://doi.org/10.1007/s00223-023-01173-1

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