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

American Journal of Nephrology
Kirk N Campbell, James A Tumlin

Abstract

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. 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 a...Continue Reading

Citations

May 2, 2019·Journal of the American Society of Nephrology : JASN·Kristina M NiculovicAnja K Münster-Kühnel
Sep 19, 2019·Médecine sciences : M/S·Hans-Kristian Lorenzo, Jean-Jacques Candelier
Mar 19, 2020·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Ariela BenigniDonald E Kohan
Dec 19, 2019·Expert Review of Clinical Pharmacology·Seyede Mina HejazianNasser Samadi
May 16, 2021·Current Opinion in Nephrology and Hypertension·J David SmeijerHiddo J L Heerspink
Aug 7, 2021·Medicina·Ana Gomez-LarrauriAlberto Ouro
Aug 6, 2021·Disease Models & Mechanisms·Gizelle M McCarthyMartin R Pollak
Aug 20, 2021·Toxicology and Applied Pharmacology·Olivier DelézayXavier Delavenne
Nov 14, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Masahiko ItohHiroyuki Sugimoto

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