Narongkiatikhun Phoom, Choi Ye Ji, Hampson Hailey, Gotzamanis Jimmy, Zhang Guanshi, van Raalte Daniel H, de Boer Ian H, Nelson Robert G, Tommerdahl Kalie L, McCown Phillip J, Kanter Jenny, Sharma Kumar, Bjornstad Petter, Saulnier Pierre Jean
Division of Endocrinology, Department of Medicine, Metabolism and Nutrition, University of Washington School of Medicine, Seattle, Washington, USA.
Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Kidney Int Rep. 2024 Oct 4;9(12):3386-3402. doi: 10.1016/j.ekir.2024.09.019. eCollection 2024 Dec.
Mitochondria are essential for cellular energy production and are implicated in numerous diseases, including diabetic kidney disease (DKD). Current evidence indicates that mitochondrial dysfunction results in alterations in several metabolic pathways within kidney cells, thereby contributing to the progression of DKD. Furthermore, mitochondrial dysfunction can engender an inflammatory milieu, leading to the activation and recruitment of immune cells to the kidney tissue, potentially perturbing intrarenal metabolism. In addition, this inflammatory microenvironment has the potential to modify immune cell metabolism, which may further accentuate the immune-mediated kidney injury. This understanding has led to the emerging field of immunometabolism, which views DKD as not just a metabolic disorder caused by hyperglycemia but also one with significant immune contributions. Targeting mitochondrial function and immunometabolism may offer protective effects for the kidneys, complementing current therapies and potentially mitigating the risk of DKD progression. This comprehensive review examines the impact of mitochondrial dysfunction and the potential role of immunometabolism in DKD. We also discuss tools for investigating these mechanisms and propose avenues for integrating this research with existing therapies. These insights underscore the modulation of mitochondrial function and immunometabolism as a critical strategy for decelerating DKD progression.
线粒体对于细胞能量产生至关重要，并且与包括糖尿病肾病（DKD）在内的多种疾病有关。目前的证据表明，线粒体功能障碍会导致肾细胞内多种代谢途径发生改变，从而促进DKD的进展。此外，线粒体功能障碍可引发炎症环境，导致免疫细胞激活并募集至肾组织，可能扰乱肾内代谢。此外，这种炎症微环境有可能改变免疫细胞代谢，这可能会进一步加重免疫介导的肾损伤。这种认识催生了免疫代谢这一新兴领域，该领域认为DKD不仅是由高血糖引起的代谢紊乱，而且也是一种有显著免疫作用的疾病。针对线粒体功能和免疫代谢可能对肾脏起到保护作用，补充当前的治疗方法，并有可能降低DKD进展的风险。这篇综述全面探讨了线粒体功能障碍的影响以及免疫代谢在DKD中的潜在作用。我们还讨论了研究这些机制的工具，并提出了将该研究与现有治疗方法相结合的途径。这些见解强调了调节线粒体功能和免疫代谢是减缓DKD进展的关键策略。
