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Am J Nephrol. 2018;47 Suppl 1:14-29. doi: 10.1159/000481634. Epub 2018 May 31.

Protecting Podocytes: A Key Target for Therapy of Focal Segmental Glomerulosclerosis.

Author information

1
Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2
Department of Medicine, UT College of Medicine, University of Tennessee, Chattanooga, Tennessee, USA.

Abstract

BACKGROUND:

Focal segmental glomerulosclerosis (FSGS) is a histologic pattern of injury demonstrated by renal biopsy that can arise from a diverse range of causes and mechanisms. It has an estimated incidence of 7 per 1 million and is the most common primary glomerular disorder leading to end-stage renal disease in the United States. This review focuses on damage to the podocyte and the consequences of this injury in patients with FSGS, the genetics of FSGS, and approaches to treatment with a focus on the effects on podocytes.

SUMMARY:

The podocyte is central to the glomerular filtration barrier and is particularly vulnerable because of its highly differentiated post-mitotic phenotype. The progressive structural changes involved in the pathology of FSGS include podocyte foot process effacement, death of podocytes and exposure of the glomerular basement membrane, filtration of nonspecific plasma proteins, expansion of capillaries, misdirected filtration at points of synechiae, and mesangial matrix proliferation. Although damage to and death of podocytes can result from single-gene disorders, evidence also suggests a role for soluble factors, such as soluble urokinase-type plasminogen activator receptor, cardiotrophin-like cytokine-1, and anti-CD40 antibodies, that promote FSGS recurrence post transplant. Several classes of medications, including corticosteroids, calcineurin inhibitors, endothelin receptor antagonists, adrenocorticotropic hormone, and rituximab, have been shown to be effective for the treatment of FSGS and have been demonstrated to have significant protective effects on podocytes. Key Messages: Greater understanding of podocyte biology is essential to the identification of new treatment targets and medications for the management of patients with FSGS.

KEYWORDS:

Podocyte; Adrenocorticotropic hormone; Calcineurin; Corticosteroid ; Proteinuria; Renal; Sclerosis

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