title: Diagnosis of complement alternative pathway disorders.
abstract: Kidney diseases resulting from abnormal control of the complement alternative pathway include atypical hemolytic uremic syndrome, C3 glomerulonephritis, and dense-deposit disease, as well as atypical postinfectious glomerulonephritis. Although clinically diverse, they all result from loss of surface or fluid-phase complement control, caused by acquired or genetic defects in the complement alternative pathway. As such, the diagnostic approach is similar and includes a comprehensive biochemical, genetic, and pathologic analysis of the complement pathway. The biochemical test battery includes functional activity measurements of the entire complement pathway, functional and quantitative analysis of individual components and regulators, and quantification of activation products. In patients with a thrombotic microangiopathy, ADAMTS-13 activity should be determined to exclude a thrombotic thrombocytopenic purpura. The spectrum of genes currently known to be involved in the pathogenesis of alternative pathway disorders is rapidly expanding. Pathologic analysis of a kidney biopsy specimen is sophisticated with ad hoc immunofluorescence studies and laser microdissection with mass spectrometry. The identification of the underlying defect in the alternative pathway based on this comprehensive analysis will allow treatment to be directed to the site of dysregulation.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Angioi
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.affiliation: Division of Anatomic Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Division of Nephrology, Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, Iowa City, Iowa, USA.
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, Iowa City, Iowa, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Smith
authors.affiliation: Clinical Biochemistry, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: David
authors.initials: D
authors.lastname: Murray
authors.affiliation: Division of Nephrology, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium.
authors.forename: Jens
authors.initials: J
authors.lastname: Van Praet
authors.affiliation: Division of Nephrology and Dialysis, Azienda Ospedaliera "G. Brotzu," Cagliari, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Pani
authors.affiliation: Division of Nephrology, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium. Electronic address: an.devriese@azsintjan.be.
authors.forename: An S
authors.initials: AS
authors.lastname: De Vriese
mesh_terms: D003170:Complement Pathway, Alternative; D006801:Humans; D007154:Immune System Diseases / Q000175:diagnosis*; D007674:Kidney Diseases / Q000175:diagnosis*
keywords: C3 glomerulopathy; C3 glomerulonephritis; alternative pathway; atypical hemolytic uremic syndrome; classical pathway; complement; dense-deposit disease; glomerulonephritis