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Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients

Melatonin is a multifaceted hormone which rises upon the onset of darkness. Pineal synthesis of melatonin is known to be disturbed in patients with end-stage renal disease, but it is not known if its production is restored to normal after successful renal transplantation. We hypothesized that urinar...

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Autores principales: van der Veen, Anna, Minović, Isidor, van Faassen, Martijn, Gomes-Neto, Antόnio W., Berger, Stefan P., Bakker, Stephan J. L., Kema, Ido P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073605/
https://www.ncbi.nlm.nih.gov/pubmed/32075158
http://dx.doi.org/10.3390/jcm9020525
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author van der Veen, Anna
Minović, Isidor
van Faassen, Martijn
Gomes-Neto, Antόnio W.
Berger, Stefan P.
Bakker, Stephan J. L.
Kema, Ido P.
author_facet van der Veen, Anna
Minović, Isidor
van Faassen, Martijn
Gomes-Neto, Antόnio W.
Berger, Stefan P.
Bakker, Stephan J. L.
Kema, Ido P.
author_sort van der Veen, Anna
collection PubMed
description Melatonin is a multifaceted hormone which rises upon the onset of darkness. Pineal synthesis of melatonin is known to be disturbed in patients with end-stage renal disease, but it is not known if its production is restored to normal after successful renal transplantation. We hypothesized that urinary excretion of 6-sulfatoxymelatonin, the major metabolite of melatonin, is lower in renal transplant recipients (RTRs) compared to healthy controls and that this is associated with excess mortality. Urinary 6-sulfatoxymelatonin was measured via LC-MS/MS in 701 stable outpatient RTRs and 285 healthy controls. Median urinary 6-sulfatoxymelatonin in RTR was 13.2 nmol/24 h, which was 47% lower than in healthy controls. Urinary 6-sufatoxymelatonin appeared undetectable in the majority of 36 RTRs with diabetic nephropathy as primary renal disease. Therefore, this subgroup was excluded from further analyses. Of the remaining 665 RTRs, during 5.4 years of follow-up, 110 RTRs died, of whom 38 died due to a cardiovascular cause. In Cox-regression analyses, urinary 6-sulfatoxymelatonin was significantly associated with all-cause mortality (0.60 (0.44–0.81), p = 0.001) and cardiovascular mortality (0.49 (0.29–0.84), p = 0.009), independent of conventional risk factors and kidney function parameters. Based on these results, evaluation and management of melatonin metabolism could be considered for improvement of long-term outcomes in RTRs.
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spelling pubmed-70736052020-03-20 Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients van der Veen, Anna Minović, Isidor van Faassen, Martijn Gomes-Neto, Antόnio W. Berger, Stefan P. Bakker, Stephan J. L. Kema, Ido P. J Clin Med Article Melatonin is a multifaceted hormone which rises upon the onset of darkness. Pineal synthesis of melatonin is known to be disturbed in patients with end-stage renal disease, but it is not known if its production is restored to normal after successful renal transplantation. We hypothesized that urinary excretion of 6-sulfatoxymelatonin, the major metabolite of melatonin, is lower in renal transplant recipients (RTRs) compared to healthy controls and that this is associated with excess mortality. Urinary 6-sulfatoxymelatonin was measured via LC-MS/MS in 701 stable outpatient RTRs and 285 healthy controls. Median urinary 6-sulfatoxymelatonin in RTR was 13.2 nmol/24 h, which was 47% lower than in healthy controls. Urinary 6-sufatoxymelatonin appeared undetectable in the majority of 36 RTRs with diabetic nephropathy as primary renal disease. Therefore, this subgroup was excluded from further analyses. Of the remaining 665 RTRs, during 5.4 years of follow-up, 110 RTRs died, of whom 38 died due to a cardiovascular cause. In Cox-regression analyses, urinary 6-sulfatoxymelatonin was significantly associated with all-cause mortality (0.60 (0.44–0.81), p = 0.001) and cardiovascular mortality (0.49 (0.29–0.84), p = 0.009), independent of conventional risk factors and kidney function parameters. Based on these results, evaluation and management of melatonin metabolism could be considered for improvement of long-term outcomes in RTRs. MDPI 2020-02-14 /pmc/articles/PMC7073605/ /pubmed/32075158 http://dx.doi.org/10.3390/jcm9020525 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
van der Veen, Anna
Minović, Isidor
van Faassen, Martijn
Gomes-Neto, Antόnio W.
Berger, Stefan P.
Bakker, Stephan J. L.
Kema, Ido P.
Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients
title Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients
title_full Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients
title_fullStr Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients
title_full_unstemmed Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients
title_short Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients
title_sort urinary excretion of 6-sulfatoxymelatonin, the main metabolite of melatonin, and mortality in stable outpatient renal transplant recipients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073605/
https://www.ncbi.nlm.nih.gov/pubmed/32075158
http://dx.doi.org/10.3390/jcm9020525
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