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C3 glomerulopathy — understanding a rare complement-driven renal disease

Smith, Richard J.H. ; Appel, Gerald B. ; Blom, Anna M. LU orcid ; Cook, H. Terence ; D’Agati, Vivette D. ; Fakhouri, Fadi ; Fremeaux-Bacchi, Véronique ; Józsi, Mihály ; Kavanagh, David and Lambris, John D. , et al. (2019) In Nature Reviews Nephrology
Abstract

The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy — dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) — have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Disease is driven by acquired factors in most patients — namely, autoantibodies that target the C3 or C5 convertases. These... (More)

The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy — dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) — have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Disease is driven by acquired factors in most patients — namely, autoantibodies that target the C3 or C5 convertases. These autoantibodies drive complement dysregulation by increasing the half-life of these vital but normally short-lived enzymes. Genetic variation in complement-related genes is a less frequent cause. No disease-specific treatments are available, although immunosuppressive agents and terminal complement pathway blockers are helpful in some patients. Unfortunately, no treatment is universally effective or curative. In aggregate, the limited data on renal transplantation point to a high risk of disease recurrence (both DDD and C3GN) in allograft recipients. Clinical trials are underway to test the efficacy of several first-generation drugs that target the alternative complement pathway.

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publication status
published
subject
in
Nature Reviews Nephrology
publisher
Nature Publishing Group
external identifiers
  • scopus:85060826830
  • pmid:30692664
ISSN
1759-5061
DOI
10.1038/s41581-018-0107-2
language
English
LU publication?
yes
id
c5493f76-220f-4689-9bdf-b777da7e01fe
date added to LUP
2019-02-13 14:11:37
date last changed
2024-06-12 07:15:29
@article{c5493f76-220f-4689-9bdf-b777da7e01fe,
  abstract     = {{<p>The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy — dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) — have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Disease is driven by acquired factors in most patients — namely, autoantibodies that target the C3 or C5 convertases. These autoantibodies drive complement dysregulation by increasing the half-life of these vital but normally short-lived enzymes. Genetic variation in complement-related genes is a less frequent cause. No disease-specific treatments are available, although immunosuppressive agents and terminal complement pathway blockers are helpful in some patients. Unfortunately, no treatment is universally effective or curative. In aggregate, the limited data on renal transplantation point to a high risk of disease recurrence (both DDD and C3GN) in allograft recipients. Clinical trials are underway to test the efficacy of several first-generation drugs that target the alternative complement pathway.</p>}},
  author       = {{Smith, Richard J.H. and Appel, Gerald B. and Blom, Anna M. and Cook, H. Terence and D’Agati, Vivette D. and Fakhouri, Fadi and Fremeaux-Bacchi, Véronique and Józsi, Mihály and Kavanagh, David and Lambris, John D. and Noris, Marina and Pickering, Matthew C. and Remuzzi, Giuseppe and de Córdoba, Santiago Rodriguez and Sethi, Sanjeev and Van der Vlag, Johan and Zipfel, Peter F. and Nester, Carla M.}},
  issn         = {{1759-5061}},
  language     = {{eng}},
  month        = {{01}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Reviews Nephrology}},
  title        = {{C3 glomerulopathy — understanding a rare complement-driven renal disease}},
  url          = {{http://dx.doi.org/10.1038/s41581-018-0107-2}},
  doi          = {{10.1038/s41581-018-0107-2}},
  year         = {{2019}},
}