Dalga Delal, Verissimo Thomas, de Seigneux Sophie
Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
Service of Nephrology, Department of Internal Medicine Specialties, University of Geneva, Geneva, Switzerland.
Clin Kidney J. 2023 Mar 14;16(8):1249-1257. doi: 10.1093/ckj/sfad046. eCollection 2023 Aug.
Chronic kidney disease (CKD) is a global health issue with increasing prevalence. Despite large improvements in current therapies, slowing CKD progression remains a challenge. A better understanding of renal pathophysiology is needed to offer new therapeutic targets. The role of metabolism alterations and mitochondrial dysfunction in tubular cells is increasingly recognized in CKD progression. In proximal tubular cells, CKD progression is associated with a switch from fatty acid oxidation to glycolysis. Glucose synthesis through gluconeogenesis is one of the principal physiological functions of the kidney. Loss of tubular gluconeogenesis in a stage-dependent manner is a key feature of CKD and contributes to systemic and possibly local metabolic complications. The local consequences observed may be related to an accumulation of precursors, such as glycogen, but also to the various physiological functions of the gluconeogenesis enzymes. The basic features of metabolism in proximal tubular cells and their modifications during CKD will be reviewed. The metabolic modifications and their influence on kidney disease will be described, as well as the local and systemic consequences. Finally, therapeutic interventions will be discussed.
慢性肾脏病（CKD）是一个全球范围内患病率不断上升的健康问题。尽管目前的治疗方法有了很大改进，但减缓CKD进展仍然是一项挑战。需要更好地理解肾脏病理生理学以提供新的治疗靶点。代谢改变和线粒体功能障碍在肾小管细胞中对CKD进展的作用日益受到认可。在近端肾小管细胞中，CKD进展与从脂肪酸氧化向糖酵解的转变有关。通过糖异生进行葡萄糖合成是肾脏的主要生理功能之一。以阶段依赖性方式丧失肾小管糖异生是CKD的一个关键特征，并导致全身以及可能的局部代谢并发症。观察到的局部后果可能与前体物质（如糖原）的积累有关，但也与糖异生酶的各种生理功能有关。本文将综述近端肾小管细胞代谢的基本特征及其在CKD过程中的改变。将描述代谢改变及其对肾脏疾病的影响，以及局部和全身后果。最后将讨论治疗干预措施。
