Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, United States.
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States.
Clin Chem. 2024 Sep 3;70(9):1172-1181. doi: 10.1093/clinchem/hvae097.
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.
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.
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.
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.
急性肾损伤（AKI）和慢性肾脏病（CKD）的诊断依赖于肌醇，但其诊断灵敏度并不理想。肾脏特异性的近端肾小管酶肌醇氧化酶（MIOX）催化肌醇（MI）转化为 D-葡萄糖醛酸。我们假设 AKI 和 CKD 中发生的近端肾小管损伤将降低 MIOX 活性，导致 MI 积累。为了探索这一点，我们开发了一种 LC-MS/MS 测定法来定量血浆 MI，并评估其在识别 AKI 和 CKD 患者方面的潜力。
我们对 3 个患者队列[正常肾功能（n=105）、CKD（n=94）和 AKI（n=54）]的血浆 MI 进行了定量。使用 Deming 回归和 Pearson 相关来确定 MI 与肌酐之间的相关性，并评估年龄、性别和种族对 MI 浓度的影响。采用受试者工作特征曲线分析评价 MI 的诊断性能。
在肾功能正常的志愿者中，血浆 MI 浓度的中心 95%百分位数范围为 16.6 至 44.2 μM。年龄、种族和性别对 MI 的影响最小。AKI 和 CKD 患者的 MI 中位数浓度较高[分别为 71.1（25 百分位数：38.2，75 百分位数：115.4）和 102.4（77，139.5）μM]。MI 对 CKD 的诊断具有优异的敏感性（98.9%）和特异性（100%）。在 AKI 患者中，MI 在肌酐之前升高 32.9（SD 16.8）h。
本研究揭示了 MI 作为一种潜在的肾脏生物标志物，在 AKI 和 CKD 期间在血浆中显著升高。MI 比血清肌酐提前升高 33 h，可用于早期 AKI 检测。有必要进一步验证和探索 MI 定量在肾脏疾病诊断中的应用。
