背景:诊断急性肾损伤(AKI)和慢性肾病(CKD)依赖于肌酐,缺乏最佳诊断灵敏度。肾脏特异性近端肾小管酶肌醇加氧酶(MIOX)催化肌醇(MI)转化为D-葡萄糖醛酸。我们假设近端肾小管损伤,发生在AKI和CKD中,会降低MIOX活性,导致MI积累。为了探索这个,我们开发了一种LC-MS/MS测定法来定量血浆MI,并评估了其在识别AKI和CKD患者方面的潜力.
方法:对3个患者队列[正常肾功能(n=105),CKD(n=94),和AKI(n=54)]。使用Deming回归和Pearson相关性以及年龄的影响来确定MI和肌酐之间的相关性。性别,和种族对MI浓度进行了评估。采用受试者工作特征曲线分析来评估MI诊断性能。
结果:在肾功能正常的志愿者中,血浆MI浓度的中心第95百分位数范围为16.6~44.2µM.年龄,种族,性别对MI的影响最小。患有AKI和CKD的患者表现出更高的中位MI浓度[71.1(第25百分位数:38.2,第75百分位数:115.4)和102.4(77,139.5)µM],分别。MI对CKD的诊断具有良好的敏感性(98.9%)和特异性(100%)。在AKI患者中,MI增加前32.9(SD16.8)h肌酐。
结论:这项研究揭示了MI作为一种潜在的肾脏生物标志物,在AKI和CKD期间血浆中显著升高。血浆MI在血清肌酐前33小时升高,实现早期AKI检测。MI定量在肾脏疾病诊断中的进一步验证和探索是必要的。
BACKGROUND: Diagnosing acute kidney injury (AKI) and chronic kidney disease (CKD) relies on creatinine, which lacks optimal diagnostic sensitivity. The kidney-specific proximal tubular enzyme myo-inositol oxygenase (MIOX) catalyzes the conversion of myo-inositol (MI) to D-glucuronic acid. We hypothesized that proximal tubular damage, which occurs in AKI and CKD, will decrease MIOX activity, causing MI accumulation. To explore this, we developed an LC-MS/MS assay to quantify plasma MI and assessed its potential in identifying AKI and CKD patients.
METHODS: MI was quantified in plasma from 3 patient cohorts [normal kidney function (n = 105), CKD (n = 94), and AKI (n = 54)]. The correlations between MI and creatinine were determined using Deming regression and Pearson correlation and the impact of age, sex, and ethnicity on MI concentrations was assessed. Receiver operating characteristic curve analysis was employed to evaluate MI diagnostic performance.
RESULTS: In volunteers with normal kidney function, the central 95th percentile range of plasma MI concentrations was 16.6 to 44.2 µM. Age, ethnicity, and sex showed minimal influence on MI. Patients with AKI and CKD exhibited higher median MI concentrations [71.1 (25th percentile: 38.2, 75th percentile: 115.4) and 102.4 (77, 139.5) µM], respectively. MI exhibited excellent sensitivity (98.9%) and specificity (100%) for diagnosing CKD. In patients with AKI, MI increased 32.9 (SD 16.8) h before creatinine.
CONCLUSIONS: This study unveils MI as a potential renal biomarker, notably elevated in plasma during AKI and CKD. Plasma MI rises 33 h prior to serum creatinine, enabling early AKI detection. Further validation and exploration of MI quantitation in kidney disease diagnosis is warranted.