Skip to main content
Public beta This website is in public beta – please give your feedback.
Nephrology

Presentation: Young person with idiopathic C3 glomerulopathy

Primary C3 glomerulopathy, sometimes known as membranoproliferative glomerulonephritis, may have a genetic cause, especially when there is family history of the condition or first-degree relatives with unexplained end-stage renal disease.

Example clinical scenario

A 16-year-old male is referred to nephrology with proteinuria, haematuria and hypertension. Investigations show nephrotic-range proteinuria and reduced eGFR with a slightly low serum C3 and negative C3 nephritic factor. His brother had been diagnosed with unexplained end-stage renal disease at age 21. Subsequent kidney biopsy is in keeping with C3 glomerulopathy (C3GN) and there is an absence of dense deposits.

When to consider genomic testing

You should consider genomic testing if your patient has idiopathic membranoproliferative glomerulonephritis (MPGN) or C3GN with onset before the age of 18 and: 

  • has a family history of MPGN/C3GN or unexplained end-stage renal disease;
  • a renal transplant is being considered; or
  • the patient is being considered for complement inhibitory therapies such as eculizumab.

There should also be no evidence of secondary cause, for example your patient could be post-infection or have a paraprotein.

C3GN is caused by variants in complement genes in only a minority of cases. There is a higher prevalence in patients with Cypriot ancestry; for further information about testing in this context see ‘Patient of Cypriot descent presents with reduced renal function and microscopic haematuria’.

A histological diagnosis of MPGN, in which immune complex deposition is prominent, does not exclude a genetic cause, but most MPGN is associated with autoimmune, infectious or proliferative disease and these should be considered and excluded first. Patients with C3 nephritic factor or dense deposits are less likely to have a genetic cause.

What do you need to do?

  • Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
  • Consider which of the following tests is best suited to your patient/family:
    • R197 Membranoproliferative glomerulonephritis including C3 glomerulopathy: This test is the first choice for patients who meet the criteria detailed above. It includes multiplex ligation-dependent probe amplification (MLPA) and a panel test comprising of genes in which variants are known to cause MPGN.
    • R240 Diagnostic testing for known variant(s): This indication can be used when a patient is clinically affected by idiopathic C3GN if a member of the family already has a known pathogenic or likely pathogenic variant. In this situation, the laboratory will only test for the known familial variant.
    • R242 Predictive testing for known familial variant(s): This indication is for a predictive (also known as presymptomatic) test that should be used for unaffected individuals who have a family member with a known pathogenic or likely pathogenic variant. This test requires authorisation from clinical genetics.
  • None of the tests outlined above use whole genome sequencing (WGS), so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion) forms.
  • Note that different forms are required for any test involving WGS.
  • Parental samples may be needed for interpretation of the child’s result. Parental samples can be taken alongside that of the child, and their DNA stored, or can be requested at a later date if needed.
  • Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
  • If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
  • Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

Resources

For clinicians

References:

For patients

↑ Back to top
  • Last reviewed: 23/12/2025
  • Next review due: 23/12/2026
  • Authors: Dr Lauren Cairns, Dr David Zocche
  • Reviewers: Dr Danielle Bogue , Dr Katherine Bull, Dr Daniel Gale, Professor Richard Sandford

Related articles