title: Focal Segmental Glomerulosclerosis.
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 etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one 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), immunofluorescence (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.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; and.|Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Avi Z
authors.initials: AZ
authors.lastname: Rosenberg
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; and.|Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000075944:Apolipoprotein L1 / Q000235:genetics; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D005938:Glucocorticoids / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use
chemical_list: C108666:APOL1 protein, human; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000075944:Apolipoprotein L1; D065095:Calcineurin Inhibitors; D005938:Glucocorticoids; D007166:Immunosuppressive Agents
keywords: Alleles; Biopsy; Body Size; Electron; Fluorescent Antibody Technique; Focal Segmental; Genetic Testing; Glomerulosclerosis; Humans; Kidney Diseases; Kidney Glomerulus; Microscopy; Mutation; Penetrance; Podocytes; Segmental glomerulosclerosis; Workload; hypertrophy; immunosuppression; kidney; kidney transplantation; nephrotic syndrome