The online version of this article (https://doi.org/10.1186/s12882-017-0802-4) contains supplementary material, which is available to authorized users.
C3 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.
Seven 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.
After 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.
Eculizumab 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.
Additional file 1: Text S1. Summary of genetic testing of patient C3GN3. Text S2. Summary of genetic testing of patient C3GN4. Text S3. Summary of genetic testing of patient DDD2. Table S1. Details on published cases with patient characteristics, and treatment response. Table S2. Details on treatment and response of patient C3GN1. Table S3. Details on treatment and response of patient C3GN2. Table S4. Details on treatment and response of patient C3GN3. Table S5. Details on treatment and response of patient DDD1. Table S6. Details on treatment and response of patient C3GN4. Table S7. Details on treatment and response of patient DDD2. Table S8. Details on treatment and response of patient C3GN5. (DOCX 155 kb)12882_2017_802_MOESM1_ESM.docx
Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Fremeaux-Bacchi V, Kavanagh D, Nester CM, Noris M, Pickering MC, Rodriguez de Cordoba S, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “kidney disease: improving global outcomes” (KDIGO) controversies conference. Kidney Int. 2017;91(3):539–51. PubMedCrossRef
- Treating C3 glomerulopathy with eculizumab
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