Genetic risk and telomere dynamics in chronic kidney disease associated with mitochondrial dysfunction and implications for Coenzyme Q10 therapy

Abstract

Chronic kidney disease (CKD) is a major global health burden characterized by progressive loss of renal function and an increased risk of cardiovascular morbidity and mortality. The risk of adverse outcomes rises with declining glomerular filtration rate, with cardiovascular disease representing the leading cause of death in advanced CKD. In addition to traditional risk factors such as diabetes and hypertension, oxidative stress and mitochondrial dysfunction have emerged as key contributors to disease pathogenesis. Oxidative stress in CKD arises from mitochondrial dysfunction and inflammation-mediated pathways, leading to endothelial dysfunction, chronic inflammation and accelerated cellular aging. Coenzyme Q10 (CoQ10), a lipid-soluble component of the mitochondrial electron transport chain, plays a central role in cellular bioenergetics and antioxidant defense. Reduced CoQ10 levels observed in CKD contribute to impaired mitochondrial function and increased oxidative damage. Genetic variation in pathways regulating oxidative stress and CoQ10 metabolism may influence CKD susceptibility. Polymorphisms such as NQO1 rs1800566 affect the reduction of CoQ10 to its active antioxidant form and may modulate individual responses to oxidative stress. Telomere shortening, a marker of biological aging, is closely associated with oxidative stress and has been linked to CKD progression. Recent advances in genomic research have enabled the development of genetic risk scores (GRS) that integrate multiple genetic variants to predict disease susceptibility. In addition, social determinants of health (SDoH), including socioeconomic and environmental factors, significantly influence CKD outcomes through their impact on biological pathways. This review synthesizes current evidence on the interplay between mitochondrial dysfunction, telomere dynamics, genetic variation and environmental influences in CKD. The therapeutic potential of CoQ10 supplementation is also discussed. Integrating molecular, genetic and social determinants provides a comprehensive framework for understanding CKD and advancing precision medicine approaches.