Vitamin D Metabolites Before and After Kidney Transplantation in Patients Who Are Anephric.

Autor: Jørgensen HS; Institute of Clinical Medicine, Aarhus University, Aarhus, and Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark., de Loor H; Department of Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Leuven University Hospitals, Leuven, Belgium., Billen J; Clinical Department of Laboratory Medicine, Leuven University Hospitals, Leuven, Belgium., Peersman N; Department of Cardiovascular Sciences, Leuven University Hospitals, Leuven, Belgium; Clinical Department of Laboratory Medicine, Leuven University Hospitals, Leuven, Belgium., Vermeersch P; Department of Cardiovascular Sciences, Leuven University Hospitals, Leuven, Belgium; Clinical Department of Laboratory Medicine, Leuven University Hospitals, Leuven, Belgium., Heijboer AC; Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, the Netherlands., Ivison F; Department of Clinical Biochemistry, Manchester University NHS Foundation Trust, Manchester, United Kingdom., Vanderschueren D; Laboratory of Clinical and Experimental Endocrinology, Leuven University Hospitals, Leuven, Belgium; KU Leuven, and Clinical Department of Endocrinology, Leuven University Hospitals, Leuven, Belgium., Bouillon R; Department of Cardiovascular Sciences, Leuven University Hospitals, Leuven, Belgium., Naesens M; Department of Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Leuven University Hospitals, Leuven, Belgium; Department of Medicine, Division of Nephrology, Leuven University Hospitals, Leuven, Belgium., Kuypers D; Department of Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Leuven University Hospitals, Leuven, Belgium; Department of Medicine, Division of Nephrology, Leuven University Hospitals, Leuven, Belgium., Evenepoel P; Department of Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Leuven University Hospitals, Leuven, Belgium; Department of Medicine, Division of Nephrology, Leuven University Hospitals, Leuven, Belgium. Electronic address: Pieter.Evenepoel@uzleuven.be.
Jazyk: angličtina
Zdroj: American journal of kidney diseases : the official journal of the National Kidney Foundation [Am J Kidney Dis] 2024 Oct; Vol. 84 (4), pp. 427-436.e1. Date of Electronic Publication: 2024 May 23.
DOI: 10.1053/j.ajkd.2024.03.025
Abstrakt: Rationale & Objective: Kidneys are vital for vitamin D metabolism, and disruptions in both production and catabolism occur in chronic kidney disease. Although vitamin D activation occurs in numerous tissues, the kidneys are the most relevant source of circulating active vitamin D. This study investigates extrarenal vitamin D activation and the impact of kidney transplantation on vitamin D metabolism in patients who are anephric.
Study Design: Case series.
Setting & Participants: Adult patients with previous bilateral nephrectomy (anephric) not receiving active vitamin D therapy evaluated at the time of (N=38) and 1 year after (n=25) kidney transplantation.
Analytical Approach: Chromatography with tandem mass spectrometry was used to measure vitamin D metabolites. Activity of CYP24A1 [24,25(OH) 2 D/25(OH)D] and CYP27B1 [1α,25(OH) 2 D/25(OH)D] is expressed as metabolic ratios. Differences between time points were evaluated by paired t-test or Wilcoxon matched-pairs signed-rank test.
Results: At time of transplantation, 1α,25(OH) 2 D was detectable in all patients (4-36pg/mL). There was a linear relationship between 25(OH)D and 1α,25(OH) 2 D levels (r=0.58, P<0.001), with 25(OH)D explaining 34% of the variation in 1α,25(OH) 2 D levels. There were no associations between 1α,25(OH) 2 D and biointact parathyroid hormone (PTH) or fibroblast growth factor 23 (FGF-23). One year after transplantation, 1α,25(OH) 2 D levels recovered (+205%), and CYP27B1 activity increased (+352%). Measures of vitamin D catabolism, 24,25(OH) 2 D and CYP24A1 activity increased 3- to 5-fold. Also, at 12 months after transplantation, 1α,25(OH) 2 D was positively correlated with PTH (ρ=0.603, P=0.04) but not with levels of 25(OH)D or FGF-23.
Limitations: Retrospective, observational study design with a small cohort size.
Conclusions: Low-normal levels of 1α,25(OH) 2 D was demonstrated in anephric patients, indicating production outside the kidneys. This extrarenal CYP27B1 activity may be more substrate driven than hormonally regulated. Kidney transplantation seems to restore kidney CYP27B1 and CYP24A1 activity, as evaluated by vitamin D metabolic ratios, resulting in both increased vitamin D production and catabolism. These findings may have implications for vitamin D supplementation strategies in the setting of kidney failure and transplantation.
Plain-Language Summary: Vitamin D activation occurs in multiple tissues, but the kidneys are considered the only relevant source of circulating levels. This study investigates vitamin D activation outside the kidneys by measuring vitamin D metabolites in 38 patients without kidneys. Active vitamin D was detectable in all patients, indicating production outside of the kidneys. There was a strong relationship between active and precursor vitamin D levels, but no association with mineral metabolism hormones, indicating that vitamin D production was more substrate dependent than hormonally regulated. One year after kidney transplantation, active vitamin D levels increased 2-fold and breakdown products increased 3-fold, indicating that production and degradation of the hormone recovers after kidney transplantation. These findings are relevant for future research into vitamin D supplementation in kidney failure.
(Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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