From the Guidelines
A decrease in complement component 3 (C3) is a significant laboratory finding that can indicate an underlying immune-mediated disorder, such as membranoproliferative glomerulonephritis or post-streptococcal glomerulonephritis 1.
Key Points
- In patients with decreased C3, treatment with eculizumab, a monoclonal antibody that inhibits complement activation, may be considered at a dose of 900mg weekly for 4 weeks, followed by 1200mg every 2 weeks 1.
- Monitoring of C3 levels is crucial in patients receiving immunosuppressive therapy, such as prednisone at a dose of 1mg/kg/day for 6-12 months, to assess treatment efficacy and potential adverse effects 1.
- A complement-dominant pattern on immunofluorescence microscopy should raise the possibility of C3 or C4 glomerulopathy (C3G, C4G) and an appropriate evaluation of the complement system should be undertaken 1.
- C3 glomerulopathy with monoclonal gammopathy is a rare entity that can present with decreased C3 levels and should be considered in patients over the age of 50 years 1.
- Repeat renal biopsy can provide additional prognostic information and assist therapeutic decisions in patients with relapse of nephritis after complete renal response, or with refractory disease 1.
From the Research
Significance of Decreased Complement 3 (C3) Levels
- Decreased Complement 3 (C3) levels are associated with various renal disorders, including atypical haemolytic uraemic syndrome (aHUS), C3 glomerulopathies (C3G), and acute antibody-mediated renal graft rejection (AMR) 2
- In C3G patients, consistently low C3 levels reflect ongoing complement activation and consumption at the C3 level, despite eculizumab treatment 2
- C3 nephritic factor (C3NeF) is an immunoglobulin G (IgG) autoantibody that binds to the complement component 3 (C3) convertase C3bBb, leading to massive C3 cleavage and low C3 levels 3
- Low serum Complement C3 levels at diagnosis of renal ANCA-associated vasculitis are associated with poor prognosis, including lower patient and death-censored renal survivals 4
- C3 glomerulonephritis (C3GN) is a disorder that typically results from abnormalities in the alternative pathway (AP) of complement, leading to glomerular injury and decreased C3 levels 5
Clinical Implications
- Decreased C3 levels are often associated with proteinuria, haematuria, and high blood pressure 3, 5
- Patients with low C3 levels may have a higher risk of progression to end-stage renal disease 4, 5
- Treatment with corticosteroids plus mycophenolate mofetil has been shown to be associated with improved renal outcomes in C3G patients 6
- Eculizumab, an anti-C5 monoclonal antibody, may be effective in treating rapidly progressive forms of C3G, but its therapeutic response is highly heterogeneous 2, 6
Complement Activation and C3 Levels
- Complement activation was assessed by analysing the haemolytic complement function of the classical (CH50) and the alternative pathway (APH50), C3 and the activation products C3d, C5a and sC5b-9 2
- C3GN results from diverse abnormalities of the alternative complement pathway leading to subsequent glomerular injury and decreased C3 levels 5
- A comprehensive complement analysis together with drug monitoring is required to distinguish mode of complement activation and efficacy of eculizumab treatment in distinct renal disorders 2