The Podocyte as a Therapeutic Target in Proteinuric Kidney Disease

Abstract

Kidney podocytes are highly differentiated cells with a complex cellular morphology. They are located inside the glomerulus, a corpuscle of capillaries through which blood is filtered hydrostatically through a high-volume/highdiscrimination filter. Neighboring podocyte Foot Processes (FP) is connected by a specialized cell-cell junction, the Slit Diaphragm (SD), which represents the main size selective filtration barrier in the kidney. The podocyte is an attractive cell for drug targeting due largely to its presence on the epithelial surface of one of the best vascularized organs in the body. Podocytes are exposed to 180 liters of filtered water and solutes each day, with the glomerular basement membrane and fenestrated glomerular endothelium not likely to be obstacles to small molecule passage. Though no podocyte-specific drugs are presently available, clinical nephrology has taken advantage of the pleitropic effects of a diverse array of therapeutic agents to treat glomerular disease. Glucocorticoids, retinoic acid, cyclosporine, abatacept, ACTH, thiazolidinedione, angiotensin converting enzyme inhibitors and rituximab have been successfully repurposed from other clinical indications to treat protein uric kidney disease. By different mechanisms these agents all nonspecifically target podocytes to promote their survival under disease conditions. This review summarizes the currently understood mechanistic basis for their use.