Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Int J Mol Sci. 2024 Mar 7;25(6):3086. doi: 10.3390/ijms25063086.
Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD), and it heightens the risk of cardiovascular incidents. The pathogenesis of DKD is thought to involve hemodynamic, inflammatory, and metabolic factors that converge on the fibrotic pathway. Genetic predisposition and unhealthy lifestyle practices both play a significant role in the development and progression of DKD. In spite of the recent emergence of angiotensin receptors blockers (ARBs)/angiotensin converting enzyme inhibitor (ACEI), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptors antagonists (NS-MRAs), current therapies still fail to effectively arrest the progression of DKD. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), a promising class of agents, possess the potential to act as renal protectors, effectively slowing the progression of DKD. Other agents, including pentoxifylline (PTF), selonsertib, and baricitinib hold great promise as potential therapies for DKD due to their anti-inflammatory and antifibrotic properties. Multidisciplinary treatment, encompassing lifestyle modifications and drug therapy, can effectively decelerate the progression of DKD. Based on the treatment of heart failure, it is recommended to use multiple drugs in combination rather than a single-use drug for the treatment of DKD. Unearthing the mechanisms underlying DKD is urgent to optimize the management of DKD. Inflammatory and fibrotic factors (including IL-1, MCP-1, MMP-9, CTGF, TNF-a and TGF-β1), along with lncRNAs, not only serve as diagnostic biomarkers, but also hold promise as therapeutic targets. In this review, we delve into the potential mechanisms and the current therapies of DKD. We also explore the additional value of combing these therapies to develop novel treatment strategies. Drawing from the current understanding of DKD pathogenesis, we propose HIF inhibitors, AGE inhibitors, and epigenetic modifications as promising therapeutic targets for the future.
糖尿病肾病（DKD）是慢性肾脏病（CKD）的主要原因，它增加了心血管事件的风险。DKD 的发病机制被认为涉及血流动力学、炎症和代谢因素，这些因素都集中在纤维化途径上。遗传易感性和不健康的生活方式在 DKD 的发展和进展中都起着重要作用。尽管最近出现了血管紧张素受体阻滞剂（ARBs）/血管紧张素转换酶抑制剂（ACEI）、钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂和非甾体类盐皮质激素受体拮抗剂（NS-MRAs），但目前的治疗方法仍未能有效阻止 DKD 的进展。胰高血糖素样肽 1 受体激动剂（GLP-1RAs）作为一种很有前途的药物类别，具有作为肾脏保护剂的潜力，可以有效减缓 DKD 的进展。其他药物，包括己酮可可碱（PTF）、selonsertib 和巴利昔替尼，由于具有抗炎和抗纤维化特性，也有望成为 DKD 的潜在治疗药物。多学科治疗，包括生活方式的改变和药物治疗，可以有效地减缓 DKD 的进展。基于心力衰竭的治疗，建议联合使用多种药物而不是单一药物治疗 DKD。揭示 DKD 的发病机制对于优化 DKD 的管理至关重要。炎症和纤维化因素（包括 IL-1、MCP-1、MMP-9、CTGF、TNF-a 和 TGF-β1）以及 lncRNAs，不仅可以作为诊断生物标志物，还可以作为治疗靶点。在这篇综述中，我们深入探讨了 DKD 的潜在机制和当前的治疗方法。我们还探讨了结合这些治疗方法开发新的治疗策略的额外价值。基于对 DKD 发病机制的现有认识，我们提出 HIF 抑制剂、AGE 抑制剂和表观遗传修饰作为未来有前途的治疗靶点。
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