Department of Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Amino Acids. 2024 Jun 6;56(1):38. doi: 10.1007/s00726-024-03400-x.
Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often alter established renal biomarkers. We studied whether amino acid enantiomers in body fluids correlate with renal function and whether they are influenced by physique or steroid medication during development. We conducted a prospective study of children 2 to 18 years old with and without CKD. We analyzed associations of serine/asparagine enantiomers in body fluids with major biochemical parameters as well as physique. To study consequences of kidney dysfunction and steroids on serine/asparagine enantiomers, we generated juvenile mice with uninephrectomy, ischemic reperfusion injury, or dexamethasone treatment. We obtained samples from 27 children, of which 12 had CKD due to congenital (n = 7) and perinatal (n = 5) causes. Plasma D-asparagine and the D/L-serine ratio had robust, positive linear associations with serum creatinine and cystatin C, and detected CKD with high sensitivity and specificity, uninfluenced by body size or biochemical parameters. In the animal study, kidney dysfunction increased plasma D-asparagine and the D/L-serine ratio, but dexamethasone treatment did not. Thus, plasma D-asparagine and the D/L-serine ratio can be useful markers for renal function in children.
生物标志物能准确反映肾功能,对于慢性肾病(CKD)的治疗至关重要。然而,在儿童中,年龄/体型和药物常常会改变既定的肾生物标志物。我们研究了体液中的氨基酸对映体是否与肾功能相关,以及它们在发育过程中是否会受到体型或类固醇药物的影响。我们对 2 至 18 岁的伴有和不伴有 CKD 的儿童进行了前瞻性研究。我们分析了体液中丝氨酸/天冬氨酸对映体与主要生化参数以及体型的关联。为了研究肾功能障碍和类固醇对丝氨酸/天冬氨酸对映体的影响,我们生成了单侧肾切除、缺血再灌注损伤或地塞米松治疗的幼年小鼠。我们从 27 名儿童中获得了样本,其中 12 名患有先天性(n=7)和围产期(n=5)病因的 CKD。血浆 D-天冬酰胺和 D/L-丝氨酸的比值与血清肌酐和胱抑素 C 呈强正线性相关,对 CKD 的检测具有高灵敏度和特异性,不受体型或生化参数的影响。在动物研究中,肾功能障碍增加了血浆 D-天冬酰胺和 D/L-丝氨酸的比值,但地塞米松治疗并未增加。因此,血浆 D-天冬酰胺和 D/L-丝氨酸的比值可作为儿童肾功能的有用标志物。