ESPN 51th Annual Meeting

ESPN 2018


 
Eculizumab for C3 glomerulopathy: effective in forms with concomitant signs of thrombotic microangiopathy
MARINA VIVARELLI 1 FRANCESCA DIOMEDI CAMASSEI 1 ALESSANDRA GIANVITI 1 ANTONIO GARGIULO 1 FRANCESCO EMMA 1

1- DIVISION OF NEPHROLOGY AND DIALYSIS, BAMBINO GESù CHILDREN’S HOSPITAL, IRCCS, ROME, ITALY
 
Introduction:

 C3 glomerulopathy (C3G) is a glomerular disorder secondary to defective control of the complement alternative pathway. Some patients have been reported to benefit from eculizumab. However, not all patients respond. Criteria for selecting C3G patients who may respond are lacking, though high circulating C5b9 may help. 

Material and methods:

 We report 4 children treated with eculizumab for different forms of C3G in our centre between 2015 and 2018.

Results:

 Pt 1 is a girl with onset of C3GN at 9 months, unresponsive to prednisone and cyclosporinA. After 9 months eculizumab was commenced and interrupted after 6 months for no improvement of proteinuria or serum albumin. Pt 2 is a girl with onset of idiopathic MPGN at 11 years of age with nephrotic-range proteinuria and hematuria, treated with i.v. methylprednisolone boli, then prednisone and mycophenolate mofetil. Only a partial reduction of proteinuria was observed. After 8-10 months she was started on eculizumab. Three months later an initial improvement in serum albumin from 2 to 2,7 g/dl was observed. Pt 3 is a boy who presented at 5 years of age with atypical hemolytic uremic syndrome, requiring dialysis. He responded rapidly to eculizumab and resumed diuresis, with nephrotic-range proteinuria and low circulating C3. His renal biopsy showed C3GN with signs of chronic thrombotic microangiopathy (TMA) evident only by electron microscopy. He responded fully with no relapse upon discontinuation of eculizumab.  Pt 4 is a boy with DDD from 8 years of age who initially responded to conventional immunosuppression. A subsequent relapse after 1 year was accompanied by low platelets with minimal signs of TMA on a repeat renal biopsy. Eculizumab was started, leading to prompt (within 1 month) reduction of proteinuria and complete remission.

Conclusions:

 In these 4 patients with features of C3G, response to eculizumab seemed to be most convincing in the presence of concomitant TMA.