Globally, diabetes is the leading cause of chronic kidney disease and end-stage renal disease, which are major risk factors for cardiovascular disease and death. Despite this burden, the factors that precipitate the development and progression of diabetic kidney disease (DKD) remain to be fully elucidated. Mitochondrial dysfunction is associated with kidney disease in nondiabetic contexts, and increasing evidence suggests that dysfunctional renal mitochondria are pathological mediators of DKD. These complex organelles have a broad range of functions, including the generation of ATP. The kidneys are mitochondrially rich, highly metabolic organs that require vast amounts of ATP for their normal function. The delivery of metabolic substrates for ATP production, such as fatty acids and oxygen, is altered by diabetes. Changes in metabolic fuel sources in diabetes to meet ATP demands result in increased oxygen consumption, which contributes to renal hypoxia. Inherited factors including mutations in genes that impact mitochondrial function and/or substrate delivery may also be important risk factors for DKD. Hence, we postulate that the diabetic milieu and inherited factors that underlie abnormalities in mitochondrial function synergistically drive the development and progression of DKD.

在全球范围内，糖尿病是导致慢性肾脏疾病和终末期肾脏疾病的主要原因，而慢性肾脏病和终末期肾脏疾病是导致心血管疾病和死亡的主要危险因素。尽管有这种负担，导致糖尿病性肾脏疾病（DKD）发生和发展的因素仍有待充分阐明。在非糖尿病环境中，线粒体功能障碍与肾脏疾病有关，越来越多的证据表明，功能异常的肾脏线粒体是DKD的病理介质。这些复杂的细胞器具有广泛的功能，包括ATP的产生。肾脏是富含线粒体的高代谢器官，其正常功能需要大量的ATP。糖尿病会改变用于产生ATP的代谢底物（例如脂肪酸和氧气）的传递。糖尿病中满足ATP需求的代谢燃料源的变化导致氧气消耗增加，这会导致肾脏缺氧。包括影响线粒体功能和/或底物传递的基因突变在内的遗传因素也可能是DKD的重要危险因素。因此，我们假设糖尿病环境和线粒体功能异常基础的遗传因素协同驱动DKD的发展和进程。