Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease: Role in Cystogenesis and Novel Therapeutic Approaches.

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent hereditary renal disorder characterized by the progressive formation of numerous fluid-filled cysts, ultimately leading to end-stage kidney disease. The results of recent studies have demonstrated that metabolic reprogramming plays a crucial role in cystogenesis and disease progression, including enhanced aerobic glycolysis, impaired fatty acid oxidation, glutamine dependence, and mitochondrial dysfunction; these metabolic alterations are regulated by signaling pathways such as mTOR, cAMP/PKA, and HIF-1α, which can modulate cell proliferation, fluid secretion, and energy metabolism. Furthermore, hypoxia and the oxidative microenvironment also promote the growth of cysts. In this review, we summarized the complex interactions between metabolic pathway alterations and key signaling cascades in ADPKD, in addition to exploring new therapeutic strategies targeting these metabolic pathways, including drug and dietary interventions. A comprehensive understanding of these mechanisms may contribute to the development of innovative treatment methods aiming to slow the disease progression of patients with ADPKD.