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Open AccessArticle

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

1
Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
2
Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(2), 525; https://doi.org/10.3390/jcm9020525
Received: 27 January 2020 / Revised: 11 February 2020 / Accepted: 12 February 2020 / Published: 14 February 2020
(This article belongs to the Special Issue Clinical Complications after Kidney Transplantation)
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. View Full-Text
Keywords: 6-Sulfatoxymelatonin; Melatonin; Kidney Transplantation; Urinary Excretion; LC-MS/MS 6-Sulfatoxymelatonin; Melatonin; Kidney Transplantation; Urinary Excretion; LC-MS/MS
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van der Veen, A.; Minović, I.; van Faassen, M.; Gomes-Neto, A.W.; Berger, S.P.; Bakker, S.J.L.; Kema, I.P. Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients. J. Clin. Med. 2020, 9, 525.

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