ESPN 50th Annual Meeting

ESPN 2017


 
Genetic and clinical characteristics of patients with C3 glomerulopathy
Rezan Topaloglu 1 Bora Gülhan 1 Emine Korkmaz 2 Ali Düzova 1 Fatih Özaltın 1 C3 Glomerulopathy Study Group 3

1- HACETTEPE UNIVERSITY FACULTY OF MEDICINE DEPARTMENT OF PEDIATRIC NEPHROLOGY, ANKARA, TURKEY
2- HACETTEPE UNIVERSITY FACULTY OF MEDICINE NEPHROGENETICS LABORATORY, ANKARA, TURKEY
3- C3 GLOMERULOPATHY STUDY GROUP, TURKEY
 
Introduction:

C3 glomerulopathy (C3G) is the recently defined pathological entity. Similar to atypical haemolytic uremic syndrome, it is associated with uncontrolled alternative complement pathway activation. Its presentation and prognosis remain largely unidentified.

Material and methods:

Presentation, progression and outcome of 19 patients (9 females, 10 males) with histopathological diagnosis of C3G were investigated. Variations in the genes encoding complement regulatory proteins (CFH, CFI, C3, MCP, CFHR5, DGKE, thrombomodulin, plasminogen) were also searched.

Results:

Mean age of pathological diagnosis was 12.3±3.6 years. At the time of biopsy nephrotic range proteinuria and non-nephrotic range proteinuria was observed in 6 and 3 patients, respectively. Microscopic or macroscopic hematuria was noted in 18 patients (94.7%). At the time of presentation, eight patients had oliguria/anuria. Low C3 level was present in 15 patients (78.9%). C3 nephritic factor was positive in three of four patients. Genetic analysis revealed at least 1 variant that might be associated with the disease in 15 patients (78.9%). Six patients (31.6%) had more than one variant in more than one gene encoding complementary regulatory proteins. Mean duration of follow-up was 1.8±1.9 years and long term follow-up was available for 18 patients. At last visit, five patients were under ACEi and/or ARB without any immunsuppressive treatment and 13 patients were under oral steroid treatment and MMF has been used concomitant with steroids in four of them. Two patients were under cyclophosphamide and steroid treatment and one patient was under steroid and cyclosporine treatment. Eculizumab has been administered to four patients and continued. In two patients, eculizumab was given one and three doses, respectively. As a result of these treatment regimes, mean serum albumin was 3.9±1.0 g/dl and mean GFR was 111±43.8 ml/min/1.73m2 at last visit. In eculizumab group (n=6) mean serum albumin and mean GFR was 3.5±1.26 g/dl and 88.4±32.5 ml/min/1.73m2, respectively. In non-eculizumab group (n=12) mean serum albumin and mean GFR was 4.1±0.9 g/dl and 123.6±45.3 ml/min/1.73m2, respectively.

Conclusions:

Variants in genes encoding complementary regulatory proteins is common in patients with C3G and eculizumab in selected patients and other treatment regimes seem to be effective. *C3G Study Group also contains authors; Esra Baskın, Oğuz Söylemezoğlu, Mehmet Bülbül, Nur Canpolat, Osman Dönmez, Gürkan Genç, Nilüfer Göknar, Umut Kavakçı, Birsin Özçakar, Alper Soylu.