Diagnosis and treatment of C3 glomerulopathy

The purpose of this review is to summarize our current understanding of the principal characteristics of C3 glomerulopathy as a framework for patient evaluation with the goal of setting the stage for a mechanistic approach to treatment. We also review published treatment experience and comment on future initiatives to devise treatment protocols for this rare renal disease patient population.

Both animal and human data support the role of the alternative pathway of complement in the C3 glomerulopathies. The finding of dominant C3 deposition on renal biopsy, a marker of aberrant complement activity and the primary diagnostic criterion, defines C3 glomerulopathy as a group of diseases that despite variable light and electron microscopy appearance, shares important phenotypic characteristics; namely the presence of genetic mutations in complement genes, the presence of C3 nephritic factors with or without other complement protein abnormalities, and finally a substantial risk for both end-stage renal disease (ESRD) and recurrence after renal transplant. Traditional immune suppressive treatment strategies are often ineffective in this group of patients. Case reports and a single small trial support the efficacy of anti-complement therapy in this setting.

The diagnosis of C3 glomerulopathy is established by renal biopsy and requires a C3 dominant pattern on immunofluorescence in a patient with active glomerulonephritis. Laboratory studies characterizing an individual patient's complement profile form the basis of an expanded phenotype that has the potential to inform not only the relative activity of disease, but also the risk for adverse outcome or treatment nonresponse. Understanding an individual patient's complement pathology will facilitate an optimal therapeutic approach to their disease.