Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement

Sanjeev Sethi, Fernando C. Fervenza, Yuzhou Zhang, Ladan Zand, Nicole C. Meyer, Nicolò Borsa, Samih H. Nasr, Richard J.H. Smith

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


Postinfectious glomerulonephritis is a common disorder that develops following an infection. In the majority of cases, there is complete recovery of renal function within a few days to weeks following resolution of the infection. In a small percentage of patients, however, the glomerulonephritis takes longer to resolve, resulting in persistent hematuria and proteinuria, or even progression to end-stage kidney disease. In some cases of persistent hematuria and proteinuria, kidney biopsies show findings of a postinfectious glomerulonephritis even in the absence of any evidence of a preceding infection. The cause of such 'atypical' postinfectious glomerulonephritis, with or without evidence of preceding infection, is unknown. Here we show that most patients diagnosed with this 'atypical' postinfectious glomerulonephritis have an underlying defect in the regulation of the alternative pathway of complement. These defects include mutations in complement-regulating proteins and antibodies to the C3 convertase known as C3 nephritic factors. As a result, the activated alternative pathway is not brought under control even after resolution of the infection. Hence, the sequela is continual glomerular deposition of complement factors with resultant inflammation and development of an 'atypical' postinfectious glomerulonephritis.

Original languageEnglish (US)
Pages (from-to)293-299
Number of pages7
JournalKidney international
Issue number2
StatePublished - Feb 2013
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported in part by NIH grant DK074409 to SS and RJHS, and Fulk Family Foundation award (Mayo Clinic) to SS. We thank Amy Weaver for help with putting the complement evaluation together.

Copyright 2018 Elsevier B.V., All rights reserved.


  • alternative pathway of complement
  • C3 glomerulonephritis
  • membranoproliferative glomerulonephritis
  • persistent glomerulonephritis
  • postinfectious glomerulonephritis

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