Pathogenesis of common glomerular diseases – role of the podocyte cytoskeleton

Takanori Kumagai, Flaviana Mouawad, Tomoko Takano

Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada

Abstract: Glomerulus is the filtration unit of the kidney where the first step of urine formation takes place. In the glomerulus, water and small molecules including waste products of the body are filtered into the urine, while large molecules essential for body function such as albumin are retained. When this barrier function of the kidney is impaired, protein leakage into the urine (proteinuria) occurs. Proteinuria is not only a hallmark of many glomerular diseases but also a prognostic marker of kidney disease progression. Visceral glomerular epithelial cells (commonly called podocytes) are known to have an important role in the maintenance of glomerular barrier function. In the last decade, remarkable progress has been made in podocyte biology, mainly led by the discoveries of important proteins that work together to maintain the intricate morphology and function of podocytes. Most of these so-called podocyte proteins modulate the actin cytoskeleton either directly or indirectly. The aim of the current review is to discuss the pathogenesis of common glomerular diseases with a particular focus on the role of the actin cytoskeleton in podocytes. The diseases covered include minimal change disease, focal segmental glomerulosclerosis (idiopathic and hereditary), membranous nephropathy, hypertensive glomerulosclerosis, and diabetic nephropathy.

Keywords: glomerular disease, podocyte, cytoskeleton, proteinuria