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Complement 3 glomerulopathy

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

Prevalence

0.2–0.3 / 100 000

660–1,000

US Estimated

900–1,350

Europe Estimated

Age of Onset

All ages

ageofonset all https://raremedicalnews.com/wp-content/uploads/2021/08/Depositphotos_125402426_L.jpg

ICD-10

Typically coded under

N04.8

Inheritance Pattern

Autosomal dominant

In some cases

rnn autosomaldominant https://raremedicalnews.com/wp-content/uploads/2021/08/Depositphotos_125402426_L.jpg

Autosomal recessive

In some cases

rnn autosomalrecessive https://raremedicalnews.com/wp-content/uploads/2021/08/Depositphotos_125402426_L.jpg

Mitochondrial/Multigenic

no https://raremedicalnews.com/wp-content/uploads/2021/08/Depositphotos_125402426_L.jpg

X-linked dominant

no https://raremedicalnews.com/wp-content/uploads/2021/08/Depositphotos_125402426_L.jpg

X-linked recessive

no https://raremedicalnews.com/wp-content/uploads/2021/08/Depositphotos_125402426_L.jpg

5 Facts you should know

FACT

1

The term C3 glomerulopathy was adopted by expert consensus in 2013 to define a group of rare kidney diseases driven by dysregulation of the complement cascade

FACT

2

C3 glomerulopathy is characterized by accumulation of the C3 component of complement in renal tissue

FACT

3

There are 2 major subgroups of C3 glomerulopathy — dense deposit disease (DDD) and C3 glomerulonephritis (C3GN)

 

FACT

4

About 50% of patients with C3G progress to kidney failure within 10 years of diagnosis

FACT

5

Factor B, factor D, and properdin (factor P) are specific components of the alternative pathway of complement activation

Complement 3 glomerulopathy is also known as...

Complement 3 glomerulopathy is also known as:

  • C3G

  • C3 glomerulopathy

  • MPGN

What’s your Rare IQ?

Which of the following diseases is believed to be mediated by the complement pathway?

Common signs & symptoms

Symptoms vary but commonly include:

  • Proteinuria
  • Hematuria
  • Swelling (edema)
  • High blood pressure
  • Fatigue
  • Reduced kidney function

Some patients develop:

  • Nephrotic syndrome
  • Progressive chronic kidney disease
  • End-stage kidney disease

Current treatments

There is no universally effective cure, and treatment focuses on slowing disease progression.

Blood pressure control

  • ACE inhibitors or ARBs

Immunosuppressive therapy in selected cases

Complement-targeting therapies (investigational or emerging)

Supportive care for kidney disease

Dialysis or kidney transplantation in advanced cases

New therapies targeting the complement system are currently under investigation.

References:

Martín B, Smith RJH. C3 Glomerulopathy. In: GeneReviews®. University of Washington, Seattle; 2018. — Describes C3G as a complement-mediated kidney disease caused by dysregulation of the alternative complement pathway and notes that inheritance is complex and only occasionally follows dominant or recessive patterns.Smith RJH, Appel GB, Blom AM, et al. C3 glomerulopathy—understanding a rare complement-driven renal disease. Nat Rev Nephrol. 2019;15:129–143. — Review discussing complement dysregulation and the role of genetic variants in complement-related genes in C3G.Piras R, et al. CFH and CFHR copy number variations in C3 glomerulopathy. Front Genet. 2021;12:670727. — Highlights the contribution of complement regulatory genes such as CFH and CFHR variants to C3G pathogenesis.Zhao W, et al. Genetic analysis of the complement pathway in C3 glomerulopathy. Nephrol Dial Transplant. 2018;33(11):1919–1927. — Reports variants in complement pathway genes including CFH, CFI, CD46, and C3 in affected patients. Heidenreich K, et al. C3 glomerulopathy: a kidney disease mediated by complement dysregulation. Front Nephrol. 2024. — Review describing the disease as caused by dysregulation of the alternative complement pathway leading to C3 deposition in glomeruli.