Diagnosis of complement alternative pathway disorders

Andrea Angioi, Fernando C. Fervenza, Sanjeev Sethi, Yuzhou Zhang, Richard J. Smith, David Murray, Jens Van Praet, Antonello Pani, An S. De Vriese

Research output: Contribution to journalShort survey

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)278-288
Number of pages11
JournalKidney international
Volume89
Issue number2
DOIs
StatePublished - Feb 1 2016

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Keywords

  • C3 glomerulonephritis
  • C3 glomerulopathy
  • alternative pathway
  • atypical hemolytic uremic syndrome
  • classical pathway
  • complement
  • dense-deposit disease
  • glomerulonephritis

ASJC Scopus subject areas

  • Nephrology

Cite this

Angioi, A., Fervenza, F. C., Sethi, S., Zhang, Y., Smith, R. J., Murray, D., Van Praet, J., Pani, A., & De Vriese, A. S. (2016). Diagnosis of complement alternative pathway disorders. Kidney international, 89(2), 278-288. https://doi.org/10.1016/j.kint.2015.12.003