Focal segmental glomerulosclerosis

Avi Z. Rosenberg, Jeffrey B. Kopp

Research output: Contribution to journalArticlepeer-review

Abstract

Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant–important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologiesarenowrecognizedasdriversofFSGS: high-penetrancegeneticFSGSduetomutationsinone of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele–associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g., glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunoflu-orescence (e.g., to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

Original languageEnglish (US)
Pages (from-to)502-517
Number of pages16
JournalClinical Journal of the American Society of Nephrology
Volume12
Issue number3
DOIs
StatePublished - 2017

Keywords

  • Alleles
  • Biopsy
  • Body Size
  • Fluorescent Antibody Technique
  • Focal Segmental
  • Genetic Testing
  • Glomerulosclerosis
  • Humans
  • Hypertrophy
  • Immunosuppression
  • Kidney
  • Kidney Diseases
  • Kidney Glomerulus
  • Kidney transplantation
  • Microscopy Electron
  • Mutation
  • Nephrotic syndrome
  • Penetrance
  • Podocytes
  • Segmental
  • Workload

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

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