Department of Pathology and Immunology, Division of Anatomic and Molecular Pathology.
Clin Chem. 2014 May;60(5):747-57. doi: 10.1373/clinchem.2013.212993. Epub 2014 Jan 31.
Acute kidney injury (AKI) affects 45% of critically ill patients, resulting in increased morbidity and mortality. The diagnostic standard, plasma creatinine, is nonspecific and may not increase until days after injury. There is significant need for a renal-specific AKI biomarker detectable early enough that there would be a potential window for therapeutic intervention. In this study, we sought to identify a renal-specific biomarker of AKI.
We analyzed gene expression data from normal mouse tissues to identify kidney-specific genes, one of which was Miox. We generated monoclonal antibodies to recombinant myo-inositol oxygenase (MIOX) and developed an immunoassay to quantify MIOX in plasma. The immunoassay was tested in animals and retrospectively in patients with and without AKI.
Kidney tissue specificity of MIOX was supported by Western blot. Immunohistochemistry localized MIOX to the proximal renal tubule. Serum MIOX, undetectable at baseline, increased 24 h following AKI in mice. Plasma MIOX was increased in critically ill patients with AKI [mean (SD) 12.4 (4.3) ng/mL, n = 42] compared with patients without AKI [0.5 (0.3) ng/mL, n = 17] and was highest in patients with oliguric AKI [20.2 (7.5) ng/mL, n = 23]. Plasma MIOX increased 54.3 (3.8) h before the increase in creatinine.
MIOX is a renal-specific, proximal tubule protein that is increased in serum of animals and plasma of critically ill patients with AKI. MIOX preceded the increases in creatinine concentration by approximately 2 days in human patients. Large-scale studies are warranted to further investigate MIOX as an AKI biomarker.
急性肾损伤（AKI）影响 45%的危重症患者，导致发病率和死亡率增加。诊断标准为血浆肌酐，其特异性差，可能要在损伤后数天才会升高。因此，非常需要一种能够早期检测到的、肾脏特异性的 AKI 生物标志物，以便为治疗干预提供潜在的时间窗口。本研究旨在寻找一种肾脏特异性的 AKI 生物标志物。
我们分析了正常小鼠组织的基因表达数据，以确定肾脏特异性基因，其中之一是 Miox。我们生成了针对重组肌醇氧化酶（MIOX）的单克隆抗体，并开发了一种免疫测定法来定量检测血浆中的 MIOX。该免疫测定法在动物模型中进行了测试，并对有和没有 AKI 的患者进行了回顾性研究。
MIOX 的肾脏组织特异性通过 Western blot 得到支持。免疫组织化学将 MIOX 定位到近端肾小管。在 AKI 后 24 小时，小鼠血清中的 MIOX 从基线时不可检测增加到 24 小时。在患有 AKI 的危重症患者中，与无 AKI 的患者（n=17，0.5[0.3]ng/ml）相比，MIOX 显著增加[n=42，12.4（4.3）ng/ml]，而少尿性 AKI 患者的 MIOX 水平最高[20.2（7.5）ng/ml，n=23]。MIOX 增加出现在肌酐增加之前 54.3（3.8）小时。
MIOX 是一种肾脏特异性的近端肾小管蛋白，在动物血清和患有 AKI 的危重症患者的血浆中增加。在人类患者中，MIOX 比肌酐浓度增加提前约 2 天。需要进行大规模研究以进一步研究 MIOX 作为 AKI 生物标志物的可能性。
