Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders

Annu Rev Pathol. 2025 Jan;20(1):329-353. doi: 10.1146/annurev-pathol-051220-092001.

Abstract

Focal segmental glomerulosclerosis (FSGS) is the morphologic manifestation of a spectrum of kidney diseases that primarily impact podocytes, cells that create the filtration barrier of the glomerulus. As its name implies, only parts of the kidney and glomeruli are affected, and only a portion of the affected glomerulus may be sclerosed. Although the diagnosis is based primarily on microscopic features, patient stratification relies on clinical data such as proteinuria and etiological criteria. FSGS affects both children and adults and has an elevated risk of progression to end-stage renal disease. The prevalence of FSGS is rising among various populations, and the efficacy of various therapies is limited. Therefore, understanding the pathophysiology of FSGS and developing targeted therapies to address the complex needs of FSGS patients are topics of great interest that are currently being studied across various clinical trials. We discuss the etiology of FSGS, describe the major contributing pathophysiological pathways, and outline emerging therapeutic strategies along with their pitfalls.

Keywords: FSGS; innate immunity; integrin; kidney; podocyte; suPAR.

Publication types

  • Review

MeSH terms

  • Animals
  • Glomerulosclerosis, Focal Segmental* / diagnosis
  • Glomerulosclerosis, Focal Segmental* / etiology
  • Glomerulosclerosis, Focal Segmental* / pathology
  • Glomerulosclerosis, Focal Segmental* / therapy
  • Humans
  • Kidney Glomerulus / pathology
  • Podocytes / pathology