#6517 CLINICOHISTOLOGICAL CHARACTERISTICS, THERAPEUTIC APPROACH AND RENAL OUTCOME IN PATIENTS WITH C3 GLOMERULOPATHY: A SINGLE-CENTER EXPERIENCE
Authors: Kapsia Eleni , Kleinaki Zoe , Michelakis Ioannis , Tsiakas Stathis , Skalioti Chrysanthi , Rokka Evangelia , Liapis George , Boletis Ioannis , Marinaki Smaragdi 
Published: June 2023

Abstract

Background and Aims
C3 glomerulopathy has been identified as a distinct disease in the last decade but it has already been associated with a high burden of end stage renal disease (ESRD). Due to the rarity and heterogeneity of the disease, data regarding the prognosis and optimal treatment are still lacking. We aimed to describe the clinical and histological phenotype of patients with C3 glomerulopathy followed at our center, the treatment regimens applied and their long-term renal outcome.

Method
We conducted a retrospective medical chart review of 19 patients with C3 glomerulopathy followed at our center and we reported clinical, histological and therapeutic parameters as well as their long-term renal outcome.

Results
Median age of patients at the time of diagnosis was 23 years (IQR 28), median proteinuria 2.6 g/d (IQR 2.8) and median eGFR 63ml/min (IQR 63). 26% of patients (5/19) presented with an eGFR &lt;30ml/min. Low serum C3 levels were reported in 11/19 patients (58%). Α monoclonal paraprotein was detected in three patients and pathogenous mutations of CFH/CFI genes in 4 out of 10 patients who underwent genetic testing. 41% of patients (7/17) were treated with RAAS inhibitors only, while 59% (10/17) received immunosuppressive treatment. Immunosuppressive treatment consisted of different combinations of steroids with mycophenolic acid, cyclophosphamide, cyclosporine or rituximab and steroid monotherapy in one patient. Treatment data were not available for two patients. There was a significant difference in baseline proteinuria between patients treated with RAAS inhibitors only (median 1.5g/d, IQR 1.14) and those who were treated with immunosuppressants (median 3.95g/d, IQR 4.8) (p = 0.003). Remission (complete or partial) was achieved by 43% of patients at 6 months and by 50% at 12 months. Median follow up time was 45 months (IQR 66). Eight patients (42%) reached ESRD in a median time of 58.5 months (IQR 62.5) while other three patients (16%) ended up with a GFR decline &gt;30%. Among patients with adverse renal outcome (ESRD, GFR decline &gt;30%), 54.5% (6/11) had baseline proteinuria &gt;3g/d, 73% (8/11) had low serum C3 and 54.5% (6/11) had interstitial fibrosis/tubular atrophy &gt;25%, while the median percentage of glomerulosclerosis was 33% (IQR 58). On the contrary, in the group of patients with favorable renal outcome, baseline proteinuria &gt;3g/d was reported in only 25% (2/8), low serum C3 in 37.5% (3/8), interstitial fibrosis/tubular atrophy &gt;25% in 25% (2/8), while median glomerulosclerosis was only 8% (IQR 15). Attainment of complete remission was associated with favorable renal outcome (p = 0.001). Five of eight patients who reached ESRD underwent kidney transplantation from a living related donor. All of them received basiliximab, mycophenolic acid, tacrolimus and steroids. Recurrence of C3 glomerulopathy was reported in four of these patients and eculizumab was given in two of them. Graft loss due to disease recurrence was observed in one patient.

Conclusion
The present case series of patients with C3 glomerulopathy highlights the great heterogeneity in the clinical phenotype, therapeutic approach and renal prognosis of the disease. It also underscores the importance of attainment of complete remission regarding the long-term renal survival. Large studies are needed in order to better define clinical and histological predictors of adverse renal outcome as well as the optimal treatment regimens.