C3 glomerulonephritis: Clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up

Sanjeev Sethi, Fernando C. Fervenza, Yuzhou Zhang, Ladan Zand, Julie A. Vrana, Samih H. Nasr, Jason D. Theis, Ahmet Dogan, Richard J.H. Smith

Research output: Contribution to journalArticlepeer-review

192 Scopus citations

Abstract

C3 glomerulonephritis (C3GN) is a recently described disorder that typically results from abnormalities in the alternative pathway (AP) of complement. Here, we describe the clinical features, kidney biopsy findings, AP abnormalities, glomerular proteomic profile, and follow-up in 12 cases of C3GN. This disorder equally affected all ages, both genders, and typically presented with hematuria and proteinuria. In both the short and long term, renal function remained stable in the majority of patients with native kidney disease. In two patients, C3GN recurred within 1 year of transplantation and resulted in a decline in allograft function. Kidney biopsy mainly showed a membranoproliferative pattern, although both mesangial proliferative and diffuse endocapillary proliferative glomerulonephritis were noted. AP abnormalities were heterogeneous, both acquired and genetic. The most common acquired abnormality was the presence of C3 nephritic factors, while the most common genetic finding was the presence of H402 and V62 alleles of Factor H. In addition to these risk factors, other abnormalities included Factor H autoantibodies and mutations in CFH, CFI, and CFHR genes. Laser dissection and mass spectrometry of glomeruli from patients with C3GN showed accumulation of AP and terminal complement complex proteins. Thus, C3GN results from diverse abnormalities of the alternative complement pathway leading to subsequent glomerular injury.

Original languageEnglish (US)
Pages (from-to)465-473
Number of pages9
JournalKidney international
Volume82
Issue number4
DOIs
StatePublished - Aug 2 2012
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.

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

Keywords

  • alternative pathway of complement
  • C3 glomerulonephritis
  • C3 glomerulopathy
  • C3GN
  • MPGN
  • proteomics

Fingerprint Dive into the research topics of 'C3 glomerulonephritis: Clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up'. Together they form a unique fingerprint.

Cite this