Autophagy and podocytopathy.

This article focuses on the role of autophagy, a lysosomal-dependent cellular degradation process, in maintaining podocyte health and its implications in podocytopathies—glomerular diseases characterized by podocyte injury such as minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Autophagy, regulated primarily by AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), helps preserve podocyte structure and function, with dysregulation contributing to podocyte damage and proteinuria. Various drugs, including aldosterone antagonists, mineralocorticoid inhibitors, vitamin D3, and metformin, have shown potential in modulating autophagy and protecting podocytes in preclinical models, though clinical trials in podocytopathies are lacking. The article highlights the complexity of autophagy measurement and cautions about adverse effects associated with some autophagy modulators, particularly mTOR inhibitors and metformin, underscoring the need for further research to develop safe and effective therapies targeting autophagy in glomerular diseases.