Diabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
Nephron. 2024;148(3):127-136. doi: 10.1159/000531823. Epub 2023 Sep 11.
Diagnosis and staging of diabetic kidney disease (DKD) via the serial assessment of routine laboratory indices lacks the granularity required to resolve the heterogeneous disease mechanisms driving progression in the individual patient. A systems nephrology approach may help resolve mechanisms underlying this clinically apparent heterogeneity, paving a way for targeted treatment of DKD.
Given the limited access to kidney tissue in routine clinical care of patients with DKD, data derived from renal tissue in preclinical model systems, including animal and in vitro models, can play a central role in the development of a targeted systems-based approach to DKD. Multi-centre prospective cohort studies, including the Kidney Precision Medicine Project (KPMP) and the European Nephrectomy Biobank (ENBiBA) project, will improve access to human diabetic kidney tissue for research purposes. Integration of diverse data domains from such initiatives including clinical phenotypic data, renal and retinal imaging biomarkers, histopathological and ultrastructural data, and an array of molecular omics (transcriptomics, proteomics, etc.) alongside multi-dimensional data from preclinical modelling offers exciting opportunities to unravel individual-level mechanisms underlying progressive DKD. The application of machine and deep learning approaches may particularly enhance insights derived from imaging and histopathological/ultrastructural data domains.
Integration of data from multiple model systems (in vitro, animal models, and patients) and from diverse domains (clinical phenotypic, imaging, histopathological/ultrastructural, and molecular omics) offers potential to create a precision medicine approach to DKD care wherein the right treatments are offered to the right patients at the right time.
通过常规实验室指标的连续评估来诊断和分期糖尿病肾病(DKD),缺乏解决导致个体患者进展的异质疾病机制所需的粒度。系统肾脏病学方法可能有助于解决这种临床明显异质性背后的机制,为 DKD 的靶向治疗铺平道路。
鉴于在 DKD 患者的常规临床护理中获得肾脏组织的机会有限,来自临床前模型系统(包括动物和体外模型)的肾脏组织中获得的数据可以在开发针对 DKD 的靶向系统方法中发挥核心作用。多中心前瞻性队列研究,包括肾脏精准医学计划(KPMP)和欧洲肾切除术生物库(ENBiBA)项目,将改善为研究目的获取人类糖尿病肾脏组织的机会。从这些计划中整合来自不同数据领域的信息,包括临床表型数据、肾脏和视网膜成像生物标志物、组织病理学和超微结构数据以及一系列分子组学(转录组学、蛋白质组学等),以及来自临床前模型的多维数据,为揭示渐进性 DKD 背后的个体机制提供了令人兴奋的机会。机器和深度学习方法的应用可能特别增强从成像和组织病理学/超微结构数据领域获得的见解。
整合来自多个模型系统(体外、动物模型和患者)和来自不同领域(临床表型、成像、组织病理学/超微结构和分子组学)的数据,为 DKD 护理提供了一种精准医学方法的潜力,即针对正确的患者在正确的时间提供正确的治疗。