title: Kidney Disease Caused by Dysregulation of the Complement Alternative Pathway: An Etiologic Approach.
abstract: Kidney diseases caused by genetic or acquired dysregulation of the complement alternative pathway (AP) are traditionally classified on the basis of clinical presentation (atypical hemolytic uremic syndrome as thrombotic microangiopathy), biopsy appearance (dense deposit disease and C3 GN), or clinical course (atypical postinfectious GN). Each is characterized by an inappropriate activation of the AP, eventuating in renal damage. The clinical diversity of these disorders highlights important differences in the triggers, the sites and intensity of involvement, and the outcome of the AP dysregulation. Nevertheless, we contend that these diseases should be grouped as disorders of the AP and classified on an etiologic basis. In this review, we define different pathophysiologic categories of AP dysfunction. The precise identification of the underlying abnormality is the key to predict the response to immune suppression, plasma infusion, and complement-inhibitory drugs and the outcome after transplantation. In a patient with presumed dysregulation of the AP, the collaboration of the clinician, the renal pathologist, and the biochemical and genetic laboratory is very much encouraged, because this enables the elucidation of both the underlying pathogenesis and the optimal therapeutic approach.
authors.affiliation: Division of Nephrology, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium; and an.devriese@azsintjan.be.
authors.forename: An S
authors.initials: AS
authors.lastname: De Vriese
authors.affiliation: Divisions of Anatomic Pathology and.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Division of Nephrology, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium; and.
authors.forename: Jens
authors.initials: J
authors.lastname: Van Praet
authors.affiliation: Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Karl A
authors.initials: KA
authors.lastname: Nath
authors.affiliation: Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
mesh_terms: D000818:Animals; D001323:Autoantibodies; D050577:Complement C3-C5 Convertases / Q000235:genetics / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000235:genetics; D017242:Complement Factor H / Q000172:deficiency* / Q000276:immunology / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000502:physiology*; D000081208:Hereditary Complement Deficiency Diseases; D006801:Humans; D007674:Kidney Diseases / Q000145:classification / Q000276:immunology* / Q000628:therapy; D015432:Glomerulonephritis, Membranoproliferative
chemical_list: D001323:Autoantibodies; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H; D050577:Complement C3-C5 Convertases
keywords: GN; complement; hemolytic uremic syndrome