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尿 D-丝氨酸水平作为预测动脉粥样硬化危险因素患者肾功能恶化的生物标志物。

Urinary D-serine level as a predictive biomarker for deterioration of renal function in patients with atherosclerotic risk factors.

机构信息

a Department of Cardiovascular Medicine, Graduate School of Medicine , Akita University , Akita , Japan.

b Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences , Nagoya University , Nagoya , Japan.

出版信息

Biomarkers. 2019 Mar;24(2):159-165. doi: 10.1080/1354750X.2018.1528632. Epub 2018 Oct 23.

Abstract

BACKGROUND

D-serine, the enantiomer of L-serine, was identified in mammals 20 years ago. Although a close relationship between D-serine and renal dysfunction has been shown, the clinical implications of urinary D- and L-serine in humans are poorly understood. The aim of this study was to evaluate the relationship between urinary D- and L-serine with well-known renal biomarkers, and clarify the prognostic value of D- and L-serine for renal events.

METHODS

This cross-sectional, prospective study included 65 patients with atherosclerotic risk factors, who were followed up for a median of 16 months. The primary endpoint was a composite of end-stage renal disease and a decline in estimated glomerular filtration rate (eGFR) ≥ 25% from baseline.

RESULTS

Urinary D-serine concentrations showed a better correlation with eGFR than did urinary L-serine, whereas neither urinary D- nor L-serine correlated with tubular markers such as urinary liver-type fatty acid-binding protein and N-acetyl-beta-D-glucosaminidase. A Cox regression analysis revealed that low urinary D-serine levels were significantly associated with the primary endpoint after adjusting for confounding factors (hazard ratio 12.60; 95% confidence interval, 3.49-45.51).

CONCLUSIONS

Urinary D-serine is associated with glomerular filtration and can be a prognostic biomarker of renal dysfunction in patients with atherosclerotic risk factors.

摘要

背景

D-丝氨酸是 L-丝氨酸的对映异构体,20 年前在哺乳动物中被发现。尽管 D-丝氨酸与肾功能障碍之间存在密切关系,但人类尿液中 D-和 L-丝氨酸的临床意义仍不清楚。本研究旨在评估尿 D-和 L-丝氨酸与已知肾生物标志物之间的关系,并阐明 D-和 L-丝氨酸对肾脏事件的预后价值。

方法

这是一项横断面前瞻性研究,纳入了 65 名具有动脉粥样硬化危险因素的患者,中位随访时间为 16 个月。主要终点是终末期肾脏疾病和估算肾小球滤过率(eGFR)从基线下降≥25%的复合终点。

结果

尿 D-丝氨酸浓度与 eGFR 的相关性优于尿 L-丝氨酸,而尿 D-丝氨酸和 L-丝氨酸均与肾小管标志物如尿肝型脂肪酸结合蛋白和 N-乙酰-β-D-氨基葡萄糖苷酶无相关性。Cox 回归分析显示,在校正混杂因素后,低尿 D-丝氨酸水平与主要终点显著相关(危险比 12.60;95%置信区间,3.49-45.51)。

结论

尿 D-丝氨酸与肾小球滤过有关,可作为动脉粥样硬化危险因素患者肾功能障碍的预后生物标志物。

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