Pereira Pedro R, Carrageta David F, Oliveira Pedro F, Rodrigues Anabela, Alves Marco G, Monteiro Mariana P
Clinical and Experimental Endocrinology, UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS, School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal.
ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal.
Med Res Rev. 2022 Jul;42(4):1518-1544. doi: 10.1002/med.21883. Epub 2022 Mar 10.
Diabetic kidney disease (DKD) is one of the most prevalent comorbidities of diabetes mellitus and the leading cause of the end-stage renal disease (ESRD). DKD results from chronic exposure to hyperglycemia, leading to progressive alterations in kidney structure and function. The early development of DKD is clinically silent and when albuminuria is detected the lesions are often at advanced stages, leading to rapid kidney function decline towards ESRD. DKD progression can be arrested or substantially delayed if detected and addressed at early stages. A major limitation of current methods is the absence of albuminuria in non-albuminuric phenotypes of diabetic nephropathy, which becomes increasingly prevalent and lacks focused therapy. Metabolomics is an ever-evolving omics technology that enables the study of metabolites, downstream products of every biochemical event that occurs in an organism. Metabolomics disclosures complex metabolic networks and provide knowledge of the very foundation of several physiological or pathophysiological processes, ultimately leading to the identification of diseases' unique metabolic signatures. In this sense, metabolomics is a promising tool not only for the diagnosis but also for the identification of pre-disease states which would confer a rapid and personalized clinical practice. Herein, the use of metabolomics as a tool to identify the DKD metabolic signature of tubule interstitial lesions to diagnose or predict the time-course of DKD will be discussed. In addition, the proficiency and limitations of the currently available high-throughput metabolomic techniques will be discussed.
糖尿病肾病(DKD)是糖尿病最常见的合并症之一,也是终末期肾病(ESRD)的主要病因。DKD是由长期暴露于高血糖引起的,导致肾脏结构和功能逐渐改变。DKD的早期发展在临床上没有症状,当检测到蛋白尿时,病变往往已处于晚期,导致肾功能迅速下降至ESRD。如果在早期阶段检测并处理,DKD的进展可以被阻止或显著延迟。当前方法的一个主要局限性是糖尿病肾病的非蛋白尿表型中不存在蛋白尿,这种表型越来越普遍且缺乏针对性治疗。代谢组学是一种不断发展的组学技术,能够研究代谢物,即生物体中发生的每个生化事件的下游产物。代谢组学揭示复杂的代谢网络,并提供有关几种生理或病理生理过程基础的知识,最终导致识别疾病独特的代谢特征。从这个意义上说,代谢组学不仅是一种有前途的诊断工具,也是一种识别疾病前期状态的工具,这将带来快速且个性化的临床实践。本文将讨论使用代谢组学作为工具来识别肾小管间质病变的DKD代谢特征,以诊断或预测DKD的病程。此外,还将讨论当前可用的高通量代谢组学技术的优势和局限性。