All patients with C3G should also undergo screening for autoantibodies:
- C3 nephritic factor (C3NeF)
- C5 nephritic factor (C5NeF)
- C4 nephritic factor (C4NeF)
- Other autoantibodies against factor H, factor B, and/or C3b
It is recommended that genetic testing be considered for patients with C3 glomerulopathy to screen for complement genes including C3, CFB, CFH, CFHR5, and CFI and copy number variations and rearrangements of the CFH-CFHR gene cluster. The value of genetic testing in the clinical setting is still being defined; however, it has been observed that patients with mutations in complement genes generally respond less favorably to mycophenolate mofetil (MMF) compared with those who are positive for nephritic factors.
Management
The patient was managed with an angiotensin-converting enzyme (ACE) inhibitor to treat proteinuria and hypertension and MMF for immunosuppression. Enrollment in a clinical trial of an investigational complement inhibitor was discussed with the patient.
Currently, there are no therapeutic agents specifically designed to target the underlying complement dysregulation that occurs in individuals with C3G, and an optimal treatment for C3 glomerulopathy has not been established.
Various nonspecific therapies have been used to treat C3G, including plasmapheresis, steroids, rituximab, cyclophosphamide, and MMF and have shown positive results. For patients with C3G who have a known genetic variant (eg, CFH mutation) or who have acute kidney injury, plasmapheresis and plasma exchange may be helpful. Using these agents judiciously and in conjunction with optimal blood pressure control is important for maximum benefit in treating C3G. When someone with end-stage renal disease (ESRD) caused by C3G chooses to have a kidney transplant, it is important to know that C3G is likely to return in almost all cases and is the leading cause of transplant failure in 50%-90% of recipients.
Prognosis
The prognosis of C3G varies and is affected by various clinical and histological factors. While some patients may have consistently low levels of protein in their urine and maintain stable kidney function over time, others may experience severe nephrotic syndrome or rapidly progressive glomerulonephritis, which often leads to a poor prognosis.
Progression to ESRD is a major complication of C3G, with approximately 70% of affected children and 30%-50% of adults reaching this stage. In addition, disease recurrence is common after kidney transplantation, with about 50% of patients experiencing allograft loss within 10 years. Predictive factors for disease progression, although not robustly established, include initial eGFR at diagnosis, percentage of tubular atrophy, and extent of interstitial fibrosis in the cortical area as observed on kidney biopsies.
Clinical Takeaways
For patients exhibiting symptoms like proteinuria and hematuria indicative of glomerulonephritis, a comprehensive evaluation including laboratory tests and a kidney biopsy is essential to confirm a C3G diagnosis through characteristic findings on immunofluorescence microscopy or electron microscopy.
Additional tests to rule out associated conditions like monoclonal gammopathy and comprehensive complement evaluation are also recommended to understand the underlying etiology and guide therapy.
Though there are no treatments specifically targeting the underlying complement dysregulation unique to C3G, nonspecific therapies like ACE inhibitors, immunosuppressants (eg, MMF), and plasmapheresis are commonly used.
Some anticomplement therapies are available or under investigation, which might offer more targeted intervention options.
The prognosis for patients with C3G can vary widely and factors such as initial eGFR, the extent of tubular atrophy, and interstitial fibrosis are important predictors of disease progression.
Dr. Alper is an associate professor, Nephrology, Tulane University School of Medicine, New Orleans, Louisiana. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.