Mitochondrial Alterations and CKD: A Review

Mitochondrial alterations are increasingly recognized as central to the pathogenesis of chronic kidney disease (CKD), contributing to impaired energy metabolism, oxidative stress, and maladaptive cellular responses. This review highlights recent advances in our understanding of mitochondrial remodeling in both diabetic and nondiabetic CKD (NDKD), including changes in bioenergetics, dynamics, redox balance, and biogenesis. We discuss state-of-the-art approaches to assess mitochondrial health, ranging from high-resolution respirometry and metabolomic profiling to transcriptomic analysis and advanced imaging techniques such as functional magnetic resonance imaging (MRI) and positron emission tomography (PET) radiotracers with metabolic readouts. Therapeutically, several agents show promise in modulating mitochondrial pathways, including sodium/glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RA), and nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), as well as emerging interventions such as glucose-dependent insulinotropic polypeptide and glucagon receptor agonist, nicotinamide adenine dinucleotide (NAD⁺) boosters, and coenzyme Q10 (CoQ10) derivatives. Multi-omics integration and spatial profiling are enabling precision phenotyping and the development of mitochondrial health scores to guide individualized therapy. Targeting mitochondrial adaptation offers a compelling avenue to improve outcomes in CKD.