Core Unit Proteomics, Institute of Toxicology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
Amino Acids. 2021 Nov;53(11):1679-1693. doi: 10.1007/s00726-021-03091-8. Epub 2021 Oct 24.
Arginine (Arg) and lysine (Lys) moieties of proteins undergo various post-translational modifications (PTM) including enzymatic N- and N-methylation and non-enzymatic N- and N-glycation. In a large cohort of stable kidney transplant recipients (KTR, n = 686), high plasma and low urinary concentrations of asymmetric dimethylarginine (ADMA), an abundant PTM metabolite of Arg, were associated with cardiovascular and all-cause mortality. Thus, the prediction of the same biomarker regarding mortality may depend on the biological sample. In another large cohort of stable KTR (n = 555), higher plasma concentrations of N-carboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL), two advanced glycation end-products (AGEs) of Lys, were associated with higher cardiovascular mortality. Yet, the associations of urinary AGEs with mortality are unknown. In the present study, we measured 24 h urinary excretion of Lys, CML, and furosine in 630 KTR and 41 healthy kidney donors before and after donation. Our result indicate that lower urinary CML and lower furosine excretion rates are associated with higher mortality in KTR, thus resembling the associations of ADMA. Lower furosine excretion rates were also associated with higher cardiovascular mortality. The 24 h urinary excretion rate of amino acids and their metabolites decreased post-donation (varying as little as - 24% for CEL, and as much as - 62% for ADMA). For most amino acids, the excretion rate was lower in KTR than in donors pre-donation [except for S-(1-carboxyethyl)-L-cysteine (CEC) and N-carboxyethylarginine (CEA)]. Simultaneous GC-MS measurement of free amino acids, their PTM metabolites and AGEs in urine is a non-invasive approach in kidney transplantation.
精氨酸（Arg）和赖氨酸（Lys）残基的蛋白质经历各种翻译后修饰（PTM），包括酶促 N-和 N-甲基化和非酶促 N-和 N-糖基化。在一大群稳定的肾移植受者（KTR，n=686）中，血浆中不对称二甲基精氨酸（ADMA）浓度高，尿液中浓度低，ADMA 是 Arg 的一种丰富的 PTM 代谢物，与心血管和全因死亡率相关。因此，同一生物标志物对死亡率的预测可能取决于生物样本。在另一大群稳定的 KTR（n=555）中，血浆中 N-羧甲基赖氨酸（CML）和 N-羧乙基赖氨酸（CEL）的浓度较高，CEL 是 Lys 的两种晚期糖基化终产物（AGEs），与较高的心血管死亡率相关。然而，尿液 AGEs 与死亡率的关联尚不清楚。在本研究中，我们测量了 630 名 KTR 和 41 名健康肾供体在捐献前后 24 小时尿中 Lys、CML 和呋塞米的排泄量。我们的结果表明，KTR 中较低的尿 CML 和较低的呋塞米排泄率与较高的死亡率相关，这类似于 ADMA 的关联。较低的呋塞米排泄率也与较高的心血管死亡率相关。氨基酸及其代谢物的 24 小时尿排泄率在捐献后降低（CEL 降低幅度最小为-24%，ADMA 降低幅度最大为-62%）。对于大多数氨基酸，KTR 的排泄率低于供体捐献前[除了 S-（1-羧乙基）-L-半胱氨酸（CEC）和 N-羧乙基精氨酸（CEA）]。同时通过 GC-MS 测量尿液中游离氨基酸、其 PTM 代谢物和 AGEs 是一种非侵入性的肾移植方法。
