Veen Anna van der, Minović Isidor, Faassen Martijn van, Gomes-Neto Antόnio W, Berger Stefan P, Bakker Stephan J L, Kema Ido P
Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.
J Clin Med. 2020 Feb 14;9(2):525. doi: 10.3390/jcm9020525.
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/24h, 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), = 0.001) and cardiovascular mortality (0.49 (0.29-0.84), = 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.
褪黑素是一种多方面作用的激素，在黑暗开始时分泌增加。已知终末期肾病患者的松果体褪黑素合成受到干扰，但肾移植成功后其分泌是否恢复正常尚不清楚。我们假设，与健康对照相比，肾移植受者（RTR）中褪黑素的主要代谢产物6-硫酸氧褪黑素的尿排泄量较低，且这与过高的死亡率相关。通过液相色谱-串联质谱法对701名稳定的门诊RTR和285名健康对照者测定尿6-硫酸氧褪黑素。RTR的尿6-硫酸氧褪黑素中位数为13.2 nmol/24小时，比健康对照者低47%。在以糖尿病肾病为原发性肾病的36名RTR中，大多数人的尿6-硫酸氧褪黑素检测不到。因此，该亚组被排除在进一步分析之外。在其余665名RTR中，在5.4年的随访期间，110名RTR死亡，其中38人死于心血管原因。在Cox回归分析中，尿6-硫酸氧褪黑素与全因死亡率（0.60（0.44 - 0.81），P = 0.001）和心血管死亡率（0.49（0.29 - 0.84），P = 0.009）显著相关，独立于传统危险因素和肾功能参数。基于这些结果，可考虑评估和管理褪黑素代谢以改善RTR的长期预后。
