title: Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis.
abstract: Focal segmental glomerulosclerosis is a histological pattern on renal biopsy caused by diverse mechanisms. In its primary form, a circulatory factor is implicated in disease onset and recurrence. The natural history of primary FSGS is unpredictable, since some patients are unresponsive towards immunosuppressive measures. Immunologic changes, leading to a proinflammatory or profibrotic milieu, have been implicated in disease progression, namely, glomerular scarring, eventually leading to end-stage renal disease. Among these, interleukin-1ß, tumor-necrosis factor-α (TNF-α), and transforming growth factor-ß1 (TGF-ß1) have emerged as important factors. Translating these findings into clinical practice dampened the enthusiasm, since both TNF-α and TGF-ß1 blockade failed to achieve significant control of the disease. More recently, a role of the complement system has been demonstrated which in fact may be another attractive target in clinical practice. Rituximab, blocking CD20-bearing cells, demonstrated conflicting data regarding efficacy in FSGS. Finally, the T-cell costimulating molecule B7-1 (CD80) is implicated in development of proteinuria in general. Blockade of this target demonstrated significant benefits in a small cohort of resistant patients. Taken together, this review focuses on immunology of FSGS, attributable to either the disease or progression, and discusses novel therapeutic approaches aiming at targeting immunologic factors.
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kronbichler
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Leierer
authors.affiliation: Pediatric Nephrology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
authors.forename: Jun
authors.initials: J
authors.lastname: Oh
authors.affiliation: Department of Nephrology, UZ Leuven, Leuven, Belgium; Department of Immunology and Microbiology, KU Leuven, Leuven, Belgium.
authors.forename: Björn
authors.initials: B
authors.lastname: Meijers
authors.affiliation: Department of Pediatric Nephrology, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Shin
mesh_terms: D018450:Disease Progression; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects; D053773:Transforming Growth Factor beta1 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha