Podocyte Metabolic Flexibility Under Stress Conditions: From Metabolic Adaptation to Maladaptive Responses

Podocytes are essential for glomerular function by maintaining the integrity of the glomerular filtration barrier. As terminally differentiated, post-mitotic cells, they are highly vulnerable to injury, which represents a central event in the development of chronic kidney disease. Although podocytes have been extensively studied to elucidate their structure and function, their metabolism and the role of metabolic dysregulation in podocyte injury remain incompletely understood. This review summarizes current knowledge of podocyte metabolism and its responses to diverse stressors. We discuss the basal metabolic profile of podocytes, which remains a matter of debate in the literature, with a focus on mitochondrial function. We further examine how stress conditions such as gluco- and lipotoxicity, vasoactive stress, mechanical stress, and immune dysregulation induce metabolic adaptations that become maladaptive upon sustained exposure. Metabolic reprogramming and its consequences, including cytoskeletal disorganization, are reviewed alongside emerging therapeutic strategies aimed at restoring podocyte metabolic homeostasis. A better understanding of podocyte metabolic flexibility may provide innovative strategies to preserve podocyte integrity and prevent the progression of chronic kidney disease.