Mitochondrial Alterations Identified as Central to Chronic Kidney Disease Pathogenesis and Emerging Therapeutic Target

Chronic kidney disease (CKD) is a global health crisis affecting 800 million people, characterized by progressive loss of kidney function. Despite diverse etiologies, common pathogenic mechanisms include apoptosis, inflammation, and fibrosis. The kidneys, with their high mitochondrial density, are highly dependent on oxidative phosphorylation for energy, making them vulnerable to metabolic disturbances. Current standard-of-care often fails to halt progression, leaving a critical gap in therapies that address the fundamental cellular dysfunction. This review highlights how mitochondrial alterations, encompassing impaired energy metabolism and oxidative stress, are pivotal drivers in CKD progression, presenting a compelling target for novel interventions.

This comprehensive review synthesized recent advances in understanding mitochondrial remodeling within both diabetic and non-diabetic CKD. Researchers systematically examined changes in mitochondrial bioenergetics, dynamics, redox balance, and biogenesis across various studies. The review also detailed state-of-the-art approaches for assessing mitochondrial health, including high-resolution respirometry, metabolomic profiling, transcriptomic analysis, functional magnetic resonance imaging (MRI), and positron emission tomography (PET) radiotracers with metabolic readouts. Furthermore, it evaluated the therapeutic potential of several agents known to modulate mitochondrial pathways.