Department of Nephrology, Government Stanley Medical College and Hospital, Chennai, Tamil Nadu, India.
Saudi J Kidney Dis Transpl. 2020 Jan-Feb;31(1):1-9. doi: 10.4103/1319-2442.279927.
Despite several decades of intensive research and hard work in nephrology, a void exists in the availability of markers for identifying at-risk individuals, diagnosing diseases at incipient stage, and predicting treatment response. Most of the current widely available diagnostic tools such as creatinine, urine analysis, and imaging studies are quite insensitive such that about half of the kidney function is lost before perceivable changes are observed with these tests. In addition, these parameters are affected by factors other than renal, questioning their specificity. Renal biopsy, though specific, is quite expensive, risky, and invasive. The recent surge in the knowledge of small molecules in the tissue and body fluids, "metabolomics," thanks to the Human Metabolome Database created by the Human Metabolome Project, has opened a new avenue for better understanding the disease pathogenesis and, in parallel, to identify novel biomarkers and druggable targets. Kidney, by virtue of its metabolic machinery and also being a major handler of metabolites generated by other tissues, is very much amenable to the metabolomic approach of studying its various perturbations. The gut microbiome, characterized by the Human Microbiome Project, is one of the principal players in metabolomics. Changes in metabolite profile due to alterations in gut microbiome can occur either as a cause or consequence of renal diseases. Unmasking the renal-metabolome-microbiome link has a great potential to script a new era in the diagnosis and management of renal diseases.
尽管肾脏病学领域经过几十年的深入研究和辛勤工作,但在识别高危人群、在早期阶段诊断疾病以及预测治疗反应的标志物方面仍然存在空白。目前大多数广泛应用的诊断工具,如肌酐、尿液分析和影像学研究,都不够敏感,以至于在这些测试中观察到可察觉的变化之前,大约一半的肾功能已经丧失。此外,这些参数受到除肾脏以外的因素的影响,这使得它们的特异性受到质疑。肾活检虽然具有特异性,但费用昂贵、风险大且具有侵入性。由于人类代谢组计划创建的人类代谢组数据库,组织和体液中小分子的知识(代谢组学)最近有了突飞猛进的发展,为更好地了解疾病发病机制开辟了新途径,并平行地确定了新的生物标志物和可药物治疗的靶点。肾脏凭借其代谢机制,以及作为其他组织产生的代谢物的主要处理者,非常适合采用代谢组学方法来研究其各种干扰。肠道微生物组是人类微生物组计划的一个特点,是代谢组学的主要参与者之一。由于肠道微生物组的改变而导致的代谢物谱的变化既可以是肾脏疾病的原因,也可以是其结果。揭示肾脏-代谢组学-微生物组之间的联系,有可能开创肾脏疾病诊断和管理的新时代。