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肾移植受者和供者中N-甲基-2-吡啶酮-5-甲酰胺和N-甲基烟酰胺的尿排泄情况

Urinary Excretion of -methyl-2-pyridone-5-carboxamide and -methylnicotinamide in Renal Transplant Recipients and Donors.

作者信息

Deen Carolien P J, van der Veen Anna, Gomes-Neto António W, Geleijnse Johanna M, Borgonjen-van den Berg Karin J, Heiner-Fokkema M Rebecca, Kema Ido P, Bakker Stephan J L

机构信息

Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.

Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.

出版信息

J Clin Med. 2020 Feb 6;9(2):437. doi: 10.3390/jcm9020437.

Abstract

-methylnicotinamide (-MN) and -methyl-2-pyridone-5-carboxamide (2Py) are successive end products of NAD catabolism. -MN excretion in 24-h urine is the established biomarker of niacin nutritional status, and recently shown to be reduced in renal transplant recipients (RTR). However, it is unclear whether 2Py excretion is increased in this population, and, if so, whether a shift in excretion of -MN to 2Py can be attributed to kidney function. Hence, we assessed the 24-h urinary excretion of 2Py and -MN in RTR and kidney donors before and after kidney donation, and investigated associations of the urinary ratio of 2Py to -MN (2Py/-MN) with kidney function, and independent determinants of urinary 2Py/-MN in RTR. The urinary excretion of 2Py and -MN was measured in a cross-sectional cohort of 660 RTR and 275 healthy kidney donors with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Linear regression analyses were used to investigate associations and determinants of urinary 2Py/-MN. Median 2Py excretion was 178.1 (130.3-242.8) μmol/day in RTR, compared to 155.6 (119.6-217.6) μmol/day in kidney donors ( < 0.001). In kidney donors, urinary 2Py/-MN increased significantly after kidney donation (4.0 ± 1.4 to 5.2 ± 1.5, respectively; < 0.001). Smoking, alcohol consumption, diabetes, high-density lipoprotein (HDL), high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) were identified as independent determinants of urinary 2Py/-MN in RTR. In conclusion, the 24-h urinary excretion of 2Py is higher in RTR than in kidney donors, and urinary 2Py/-MN increases after kidney donation. As our data furthermore reveal strong associations of urinary 2Py/-MN with kidney function, interpretation of both -MN and 2Py excretion may be recommended for assessment of niacin nutritional status in conditions of impaired kidney function.

摘要

-甲基烟酰胺(-MN)和-甲基-2-吡啶酮-5-羧酰胺(2Py)是烟酰胺腺嘌呤二核苷酸(NAD)分解代谢的连续终产物。24小时尿中-MN排泄量是已确立的烟酸营养状况生物标志物,最近研究表明肾移植受者(RTR)的该指标降低。然而,尚不清楚该人群中2Py排泄量是否增加,以及如果增加,-MN排泄向2Py的转变是否可归因于肾功能。因此,我们评估了肾移植受者和肾供者在肾移植前后24小时尿中2Py和-MN的排泄情况,并研究了2Py与-MN的尿排泄比值(2Py/-MN)与肾功能的关联,以及肾移植受者尿2Py/-MN的独立决定因素。采用液相色谱-串联质谱法(LC-MS/MS)测定了660例肾移植受者和275例健康肾供者横断面队列中的2Py和-MN尿排泄量。采用线性回归分析研究尿2Py/-MN的关联和决定因素。肾移植受者的2Py排泄中位数为178.1(130.3 - 242.8)μmol/天,而肾供者为155.6(119.6 - 217.6)μmol/天(P < 0.001)。在肾供者中,肾移植后尿2Py/-MN显著增加(分别从4.0 ± 1.4增至5.2 ± 1.5;P < 0.001)。吸烟、饮酒、糖尿病、高密度脂蛋白(HDL)、高敏C反应蛋白(hs-CRP)和估计肾小球滤过率(eGFR)被确定为肾移植受者尿2Py/-MN的独立决定因素。总之,肾移植受者24小时尿2Py排泄量高于肾供者,肾移植后尿2Py/-MN增加。由于我们的数据还揭示了尿2Py/-MN与肾功能的强烈关联,因此在肾功能受损的情况下,建议同时解读-MN和2Py排泄量以评估烟酸营养状况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce0/7074074/5367a8ad93b3/jcm-09-00437-g001.jpg

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