Use of gas chromatography mass spectrometry to elucidate metabolites predicting the phenotypes of IgA nephropathy in hyper IgA mice

IgA nephropathy, a common chronic kidney disease, has various possible outcomes. Therefore, the identification of novel prognostic biomarkers is needed. To this purpose, we used gas chromatography mass spectrometry to search for metabolites capable of predicting the phenotypes of IgA nephropathy in hyper IgA (HIGA) mice, an established model mice for IgA nephropathy. We measured the plasma metabolite levels in 12- and 22-week-old mice, prior to the manifestation of IgA nephropathy phenotypes, and statistically investigated the associations between these metabolites and the phenotypes of IgA nephropathy, such as the urine protein levels and histological phenotypes of the kidney at 32 weeks. We observed that in plasma samples collected from 12- and 22-week-old HIGA mice, the urinary protein levels were significantly associated with 8 and 10 metabolites, the glomerular cellular component levels were significantly associated with 8 and 7 metabolites, and the mesangial substrate levels were significantly associated with 8 and 8 metabolites, respectively. Among the candidate metabolites associated with the phenotypes of IgA nephropathy, coniferyl alcohol levels were significantly higher in HIGA mice at all of the 12, 22, and 32 weeks of age. Since this study was an observational study, we could not elucidate the underlying mechanisms; however, we were able to identify new candidate metabolites, such as coniferyl alcohol, as being potentially involved in the pathogenesis of IgA nephropathy. These results might help to develop novel laboratory tests and therapeutic reagents for IgA nephropathy in the future.IgA肾病（IgA nephropathy）是一类常见的慢性肾脏病，存在多种转归结局，因此亟需发掘新型预后生物标志物。为达成此研究目标，本研究采用气相色谱-质谱联用（gas chromatography mass spectrometry）技术，以已成熟的IgA肾病模型小鼠——高IgA（hyper IgA, HIGA）小鼠为研究对象，筛选可预测IgA肾病表型的代谢物。研究人员在IgA肾病表型显现前的12周龄与22周龄阶段，检测了小鼠血浆代谢物水平，并针对32周龄时的IgA肾病表型（如尿蛋白水平、肾脏组织学表型）与上述代谢物的关联开展统计学分析。结果显示，在12周龄与22周龄HIGA小鼠的血浆样本中，尿蛋白水平分别与8种、10种代谢物显著相关；肾小球细胞组分水平分别与8种、7种代谢物显著相关；系膜基质水平分别与8种、8种代谢物显著相关。在与IgA肾病表型相关的候选代谢物中，阿魏醇（coniferyl alcohol）在12、22及32周龄的HIGA小鼠体内均呈现显著高表达。由于本研究属于观察性研究，未能阐明其潜在分子机制，但本研究成功鉴定出阿魏醇等新型候选代谢物，其可能参与IgA肾病的发病进程。上述研究结果未来或可助力IgA肾病新型实验室检测手段与治疗药物的开发。