Miguel Verónica, Shaw Isaac W, Kramann Rafael
Department of Medicine 2, Nephrology, Rheumatology and Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany.
Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands.
Nat Rev Nephrol. 2025 Jan;21(1):39-56. doi: 10.1038/s41581-024-00889-z. Epub 2024 Sep 17.
Chronic kidney disease (CKD), defined as persistent (>3 months) kidney functional loss, has a growing prevalence (>10% worldwide population) and limited treatment options. Fibrosis driven by the aberrant accumulation of extracellular matrix is the final common pathway of nearly all types of chronic repetitive injury in the kidney and is considered a hallmark of CKD. Myofibroblasts are key extracellular matrix-producing cells that are activated by crosstalk between damaged tubules and immune cells. Emerging evidence indicates that metabolic alterations are crucial contributors to the pathogenesis of kidney fibrosis by affecting cellular bioenergetics and metabolite signalling. Immune cell functions are intricately connected to their metabolic characteristics, and kidney cells seem to undergo cell-type-specific metabolic shifts in response to damage, all of which can determine injury and repair responses in CKD. A detailed understanding of the heterogeneity in metabolic reprogramming of different kidney cellular subsets is essential to elucidating communication processes between cell types and to enabling the development of metabolism-based innovative therapeutic strategies against CKD.
慢性肾脏病（CKD）定义为持续性（>3个月）肾功能丧失，其患病率不断上升（全球人口>10%）且治疗选择有限。由细胞外基质异常积聚驱动的纤维化是肾脏几乎所有类型慢性重复性损伤的最终共同途径，被认为是CKD的一个标志。肌成纤维细胞是产生细胞外基质的关键细胞，通过受损肾小管与免疫细胞之间的相互作用而被激活。新出现的证据表明，代谢改变通过影响细胞生物能量学和代谢物信号传导，是肾脏纤维化发病机制的关键因素。免疫细胞功能与其代谢特征密切相关，肾脏细胞似乎会因损伤而发生细胞类型特异性的代谢转变，所有这些都可以决定CKD中的损伤和修复反应。详细了解不同肾脏细胞亚群代谢重编程的异质性，对于阐明细胞类型之间的通讯过程以及开发基于代谢的针对CKD的创新治疗策略至关重要。
