Treating C3 glomerulopathy with eculizumab

Abstract

BackgroundC3 glomerulopathy (C3G) is a rare, but severe glomerular disease with grim prognosis. The complex pathogenesis is just unfolding, and involves acquired as well as inherited dysregulation of the alternative pathway of the complement cascade. Currently, there is no established therapy. Treatment with the C5 complement inhibitor eculizumab may be a therapeutic option. However, due to rarity of the disease, parameters predicting treatment response remain largely unknown.MethodsSeven patients with C3G (five with C3 glomerulonephritis and two with dense deposit disease) were treated with eculizumab. Subjects underwent biopsy before enrollment. The histopathology, clinical data, and response to eculizumab treatment were analyzed. The key parameters to determine outcome were changes of serum creatinine and urinary protein over time.ResultsAfter treatment with eculizumab, four subjects showed significantly improved or stable renal function and urinary protein. A positive response occurred between 2 weeks and 6 months after therapy initiation. One subject (with allograft recurrent C3 glomerulonephritis) initially showed a positive response, but relapsed when eculizumab was discontinued, and did not respond after re-initiation of treatment. Two subjects showed impaired renal function and increasing urinary protein despite therapy with eculizumab.ConclusionsEculizumab may be a therapeutic option for a subset of C3G patients. The response to eculizumab is heterogeneous, and early as well as continuous treatment may be necessary to prevent disease progression. These findings emphasize the need for studies identifying genetic and functional complement abnormalities that may help to guide eculizumab treatment and predict response.Electronic supplementary materialThe online version of this article (10.1186/s12882-017-0802-4) contains supplementary material, which is available to authorized users.

Clinical features and potential relevant factors of renal involvement in primary Sjögren’s syndrome

“…The reasons are still unclear, and further studies are required. It’s presumed that uncontrolled activation of the complement pathway leads to predominantly glomerular deposition of C3, which is called C3 glomerulopathy . Based on that, we believe reduced C3 levels, as a result of overconsuming, may be highly associated with renal involvement.…”

Evaluation of Clinical, Laboratory and Treatment Modalities in C3 Glomerulopathy: Single Center Experience

“…reported that creatinine level in one transplant recipient remained stable and in two transplant recipients was improved. Proteinuria remained stable in one patient and decreased in two patients [26].…”

Cutaneous Vasculitis and Digital Ischaemia Caused by Heterozygous Gain-of-Function Mutation in C3

“…Eculizumab is a humanized monoclonal antibody that binds C5 and prevents assembly of the membrane attack complex (C5b-9) thereby blocking the final complement cascade and reducing uncontrolled activation of the alternative complement pathway ( 35 ). Several case reports and open-label studies have already shown a potential benefit of eculizumab for patients with C3 glomerulonephritis and aHUS where there is an acquired dysregulation of complement factors ( 35 – 38 ). In addition, avacopan, a C5a receptor inhibitor, downregulates activation of the alternative complement pathway and has been shown to be an effective add-on therapy for ANCA associated vasculitis ( 39 , 40 ).…”