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.

中文翻译：

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LC-MS/MS 对急性肾损伤和慢性肾病患者血液肌醇的临床应用。


背景诊断急性肾损伤（AKI）和慢性肾病（CKD）依赖于肌酐，但肌酐缺乏最佳的诊断敏感性。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 AKI 和 CKD 中发生的近端肾小管损伤会降低 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 测定法来量化血浆 MI，并评估其在识别 AKI 和 CKD 患者方面的潜力。方法 对 3 个患者队列 [肾功能正常 (n = 105)、CKD (n = 94) 和 AKI (n = 54)] 的血浆中的 MI 进行定量。使用戴明回归和皮尔逊相关性确定 MI 和肌酐之间的相关性，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 浓度的中央 95% 范围为 16.6 至 44.2 µM。年龄、种族和性别对 MI 的影响很小。 AKI 和 CKD 患者表现出较高的中位 MI 浓度 [分别为 71.1（第 25 个百分位：38.2，第 75 个百分位：115.4）和 102.4（77, 139.5）μM]。 MI 对诊断 CKD 表现出出色的敏感性 (98.9%) 和特异性 (100%)。在 AKI 患者中，MI 比肌酐升高 32.9 (SD 16.8) 小时。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 期间血浆中显着升高。血浆 MI 比血清肌酐先升高 33 小时，从而能够早期检测到 AKI。 MI 定量在肾脏疾病诊断中的进一步验证和探索是必要的。