Helmersson-Karlqvist Johanna, Ärnlöv Johan, Carlsson Axel C, Lind Lars, Larsson Anders
Department of Medical Sciences, Uppsala University, Sweden.
Department of Medical Sciences, Uppsala University, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
Clin Biochem. 2016 Oct;49(15):1164-1166. doi: 10.1016/j.clinbiochem.2016.07.015. Epub 2016 Jul 28.
The interest for tubular damage markers such as urinary cystatin C (U-CystC) and kidney injury molecule-1 (U-KIM-1) grows, especially for the diagnosis of acute kidney injury. The trend to measure proteins in spot urine samples instead of 24-h urine collections calls for adjustment of urine dilution with urinary creatinine (UCr). However, it is not known whether UCr adjustment provides a more true value of basal U-CystC and U-KIM-1 levels than absolute values.
DESIGN & METHODS: This study examines the rationale for UCr correction for U-CystC and U-KIM-1 by exploring the linear relations between U-CystC and U-KIM-1 and UCr, respectively, and the biological day to day variation of absolute concentrations and UCr adjusted values of the two biomarkers.
Both U-CystC and U-KIM-1 concentrations correlated positively with UCr (R=0.37, P<0.001 and R=0.62, P<0.001, respectively) in 378 participants in a community cohort, which indicated a rationale for adjustment with UCr. However, U-CystC/Cr ratio associated negatively with UCr (R=- 0.31, P<0.001), which could indicate a certain amount of 'over-adjustment'. Morning urine collected for 10 consecutive days from 13 healthy volunteers showed a biological day to day variation of 82% for U-CystC, 75% for U-cystC/Cr ratio, 70% for U-KIM-1 and 46% for U-KIM-1/Cr ratio.
This study supports the use of U-KIM-1/Cr ratio in clinical population studies. Data supporting the use of U-CysC/U-Cr ratio were less convincing and the possible confounding of UCr has to be acknowledged in clinical settings.
对诸如尿胱抑素C(U-CystC)和肾损伤分子-1(U-KIM-1)等肾小管损伤标志物的关注日益增加,尤其是在急性肾损伤的诊断方面。用即时尿样而非24小时尿液收集来检测蛋白质的趋势,要求用尿肌酐(UCr)来调整尿液稀释度。然而,尚不清楚UCr调整后得出的基础U-CystC和U-KIM-1水平是否比绝对值更具真实价值。
本研究通过分别探究U-CystC与U-KIM-1和UCr之间的线性关系,以及这两种生物标志物绝对浓度和UCr校正值的每日生物学变化,来研究对U-CystC和U-KIM-1进行UCr校正的基本原理。
在一个社区队列的378名参与者中,U-CystC和U-KIM-1浓度均与UCr呈正相关(R分别为0.37,P<0.001和R为0.62,P<0.001),这表明有理由用UCr进行调整。然而,U-CystC/Cr比值与UCr呈负相关(R = -0.31,P<0.001),这可能表明存在一定程度的“过度调整”。从13名健康志愿者连续10天收集的晨尿显示,U-CystC的每日生物学变化为82%,U-cystC/Cr比值为75%,U-KIM-1为70%,U-KIM-1/Cr比值为46%。
本研究支持在临床人群研究中使用U-KIM-1/Cr比值。支持使用U-CysC/U-Cr比值的数据说服力较弱,在临床环境中必须认识到UCr可能存在的混杂因素。