Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Int J Mol Sci. 2024 Oct 10;25(20):10882. doi: 10.3390/ijms252010882.
Among all nephropathies, diabetic kidney disease (DKD) is the most common cause of kidney impairment advancement to end-stage renal disease (ESRD). Although DKD has no cure, the disease is commonly managed by strict control of blood glucose and blood pressure, and in most of these cases, kidney function often deteriorates, resulting in dialysis, kidney replacement therapy, and high mortality. The difficulties in finding a cure for DKD are mainly due to a poor understanding of the underpinning complex cellular mechanisms that could be identified as druggable targets for the treatment of this disease. The review is thus aimed at giving insight into the interconnection between chronic hyperglycaemia and cellular mechanistic perturbations of nephropathy in diabetes. A comprehensive literature review of observational studies on DKD published within the past ten years, with 57 percent published within the past three years was carried out. The article search focused on original research studies and reviews published in English. The articles were explored using Google Scholar, Medline, Web of Science, and PubMed databases based on keywords, titles, and abstracts related to the topic. This article provides a detailed relationship between hyperglycaemia, oxidative stress, and various cellular mechanisms that underlie the onset and progression of the disease. Moreover, it also shows how these mechanisms affect organelle dysfunction, resulting in fibrosis and podocyte impairment. The advances in understanding the complexity of DKD mechanisms discussed in this review will expedite opportunities to develop new interventions for treating the disease.
在所有的肾脏病中，糖尿病肾病（DKD）是导致肾功能进展为终末期肾病（ESRD）的最常见原因。尽管 DKD 无法治愈，但该疾病通常通过严格控制血糖和血压来管理，而在大多数情况下，肾功能往往会恶化，导致透析、肾脏替代治疗和高死亡率。DKD 治疗困难的主要原因是对潜在的复杂细胞机制了解不足，这些机制可以被确定为治疗该疾病的可用药靶。因此，本综述旨在深入了解慢性高血糖与糖尿病肾病中细胞机制的失调之间的联系。对过去十年内发表的关于 DKD 的观察性研究进行了全面的文献综述，其中 57%的研究是在过去三年内发表的。文章搜索主要集中在与主题相关的关键词、标题和摘要的原创研究和综述上。这篇文章详细阐述了高血糖、氧化应激与疾病发生和进展相关的各种细胞机制之间的关系。此外，它还展示了这些机制如何影响细胞器功能，导致纤维化和足细胞损伤。本文讨论了对 DKD 机制复杂性的深入理解，这将加速为治疗该疾病开发新干预措施的机会。
