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Factors associated with 1,25-dihydroxyvitamin D3 concentrations in liver transplant recipients: a prospective observational longitudinal study

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Abstract

The aim of the study was to identify factors associated with 1,25(OH)2D3 concentrations in liver transplant recipients with emphasis on the renal function and catabolism. We also tested the hypothesis that tacrolimus increases 1,25(OH)2D3 concentrations. Serum 25(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 were measured in 41 patients before, at 2 weeks and 3 months after transplantation. Dose-adjusted tacrolimus concentration was used as a surrogate marker of CYP3A4 activity. Factors associated with 1,25(OH)2D3 were identified using multivariate linear regression analysis. The median 1,25(OH)2D3 levels remained stable: 55 versus 46 pg/ml (P = 0.36) despite an increase in 25(OH)D3 from 18 ng/ml at baseline to 26 ng/ml (P = 0.03), serum albumin (34 to 41 g/l, P = 0.02), and comparable eGFR at baseline and month 3 (94 and 92 ml/min, respectively, P = 0.15). At 3 months 19 % of patients had 1,25(OH)2D3 < 25 pg/ml. Low eGFR and a low dose-adjusted tacrolimus concentration were both independently associated with 1,25(OH)2D3 at 3 months. Liver transplant recipients with impaired renal function or a low dose-adjusted tacrolimus concentration suggesting a high CYP3A4 are at risk of low 1,25(OH)2D3 concentrations. The use of tacrolimus does not lead to an increase in 1,25(OH)2D3 concentrations in a clinical setting.

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Abbreviations

25(OH)D3 :

25-Hydroxyvitamin D3

1,25(OH)2D3 :

1,25-Dihydroxyvitamin D3

VDBP:

Vitamin D binding protein

PTH:

Parathyroid hormone

TAC C0:

Tacrolimus pre-dose concentrations

LC–MS/MS:

Liquid chromatography-tandem mass spectroscopy

CV:

Coefficient of variation

LOQ:

Limit of quantification

24,25(OH)2D3 :

24R,25-dihydroxyvitamin D3

CKD-EPI:

Chronic Kidney Disease Epidemiology Collaboration

eGFR:

Estimated glomerular filtration rate

MELD:

Model for end-stage liver disease

IQR:

Interquartile range

Ln:

Logarithm

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Acknowledgments

The authors would like to thank Mrs. Elien Glorieus and Mrs. Kaatje Toye for their logistic support. AP has been supported by the Clinical Research Grant funded by the University of Ghent. HvV is a senior clinical investigator of the Fund for Scientific Research Flanders, Belgium.

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Authors and Affiliations

  1. Pediatric Nephrology and Rheumatology Department, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Agnieszka Prytuła, Johan Vande Walle, Jo Dehoorne & Ann Raes

  2. Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium

    Hans Van Vlierberghe

  3. Department of Endocrinology, Ghent University Hospital, Ghent, Belgium

    Jean-Marc Kaufman

  4. Department of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium

    Tom Fiers

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  1. Agnieszka Prytuła
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Prytuła, A., Walle, J.V., Van Vlierberghe, H. et al. Factors associated with 1,25-dihydroxyvitamin D3 concentrations in liver transplant recipients: a prospective observational longitudinal study. Endocrine 52, 93–102 (2016). https://doi.org/10.1007/s12020-015-0757-9

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