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Body composition, adipokines, FGF23-Klotho and bone in kidney transplantation: Is there a link?

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Abstract

Background

Kidney transplantation—associated mineral and bone disorder (KT-MBD) still represents a black box on the long-term due to scarce available data. We aimed to investigate the impact of non-classical bone regulating factors (body composition, adipokines, inflammatory markers, fibroblast growth factor 23—FGF23 and α-Klotho) in long-standing kidney transplant (KT) recipients compared to the general population.

Methods

Our cross-sectional study, enrolling 59 KT patients and age, sex and body mass index—matched healthy general population volunteers, assessed the predictive role of the body composition, serum adipokines (leptin, adiponectin, resistin), inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and parathyroid hormone (PTH)—FGF23/α-Klotho axis upon bone mineral density (BMD) and osteocalcin, using correlation and linear multiple regression.

Results

The 59 KT recipients (mean transplantation span of 57.7 ± 7.2 months) had similar body composition but significantly lower BMD (p < 0.01) compared to the general population group. Total lean mass was independently associated with BMD in both groups. In KT patients, age, time spent on dialysis and PTH were the main negative independent predictors of BMD, after adjusting for possible confounders. Resistin and α-Klotho also negatively predicted lumbar bone density (p < 0.001), while adiponectin and α-Klotho positively predicted osteocalcin levels (p < 0.001) in KT recipients, independently of inflammatory markers. No significant associations were found between FGF23 and bone parameters in any of the groups.

Conclusions

Age, PTH, time on dialysis and lean mass are among the main bone density predictors in long-standing KT patients. The bone impact of adipokine dysregulation and of α-Klotho merits further investigations in KT-MBD. Preserving lean mass for improved bone outcomes should be part of KT-MBD management on the long-term.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We are grateful to Mr. Valentin Zaharia and Mr. Adrian Aancute for excellent technical assistance.

Funding

This work was financed by the “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania under an internal Grant [27494/20.12.2018].

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Author notes

  1. Anca Matei and Stefana Catalina Bilha contributed equally to the paper.

Authors and Affiliations

  1. Endocrinology Department, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, No. 16 University Street, 700115, Iasi, Romania

    Anca Matei, Stefana Catalina Bilha & Dumitru D. Branisteanu

  2. Immunology Department, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, No. 16 University Street, 700115, Iasi, Romania

    Daniela Constantinescu, Mariana Pavel-Tanasa & Petru Cianga

  3. Nephrology Department, Dialysis and Renal Transplant Center, “C.I. Parhon” University Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, No. 16 University Street, 700115, Iasi, Romania

    Adrian Covic

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  1. Anca Matei
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Contributions

AM and SCB contributed to the research design and performance, data analysis and writing of the paper. DC and MPT performed laboratory determinations and data analysis. PC performed laboratory determinations and revised the paper. AC and DDB performed the research design, drafted and revised the paper. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Adrian Covic.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

The study adhered to the Declaration of Helsinki and the Declaration of Istanbul. The institutional ethics committee approved the protocol (20.03.2019).

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All individual participants gave written informed consent before entering the study.

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All individual participants gave written informed consent regarding publishing their data before entering the study.

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Matei, A., Bilha, S.C., Constantinescu, D. et al. Body composition, adipokines, FGF23-Klotho and bone in kidney transplantation: Is there a link?. J Nephrol 35, 293–304 (2022). https://doi.org/10.1007/s40620-021-00972-9

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  • DOI: https://doi.org/10.1007/s40620-021-00972-9

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