Abstract: SA-PO215
Eculizumab for the Treatment of Recurrent C3 Glomerulonephritis Caused by a C3 Gain of Function Mutation
Session Information
- Trainee Case Reports - V
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Kim, Joon S., University of Nebraska Medical Center , Omaha, Nebraska, United States
- Mullane, Ryan, University of Nebraska Medical Center, Omaha, Nebraska, United States
- Westphal, Scott G., University of Nebraska Medical Center-Nebraska Medicine, Omaha, Nebraska, United States
- Langewisch, Eric D., University of Nebraska Medical Center, Omaha, Nebraska, United States
- Miles, Clifford D., University of Nebraska Medical Center, Omaha, Nebraska, United States
Introduction
C3 glomerulonephritis (C3GN) is a glomerular disease caused by excessive activation of the alternative complement pathway and often leads to end-stage renal disease. Following kidney transplantation, the recurrence risk is high and may cause premature allograft failure. Eculizumab prevents the membrane attack complex (MAC) formation and provides terminal complement inhibition. Here we present a case of early recurrent post-transplant C3GN in a patient with a C3 gene mutation that was successfully treated with eculizumab.
Case Description
A 38 year old female with a history of chronic kidney disease received a living unrelated kidney transplant. Prior to her transplant, she was diagnosed with C3GN which was refractory to corticosteroids, mycophenolate, and rituximab. Evaluation revealed a C3 gain of function mutation. Complement inhibitory factors were normal and she did not have a C3 nephritic factor. An elevated level of soluble MAC (sMAC) was noted prior to transplantation.
She had immediate graft function following her transplant and she was maintained on tacrolimus, mycophenolate, and prednisone following basiliximab induction. Her creatinine reached a nadir of 1.1 mg/dl, but she developed early acute allograft dysfunction and proteinuria within the first few weeks of transplant and biopsy revealed early recurrence of C3GN. She was treated with high dose corticosteroids and plasmapheresis, but continued progression of renal dysfunction with rising sMAC levels, proteinuria, and activity of C3GN on a repeat biopsy.
After initiation of eculizumab, her sMAC levels normalized, proteinuria resolved, and the allograft function improved. She is now >1 year out from transplantation with stable allograft function and no evidence of complications related to the eculizumab.
Discussion
Eculizumab appears to have a role in select patients with recurrent C3GN. Since not all patients with C3GN improve with eculizumab, more research is needed to define patients expected to benefit from this therapy. Patients with recurrent C3GN due to a gain of function mutation in the C3 gene should be considered for early eculizumab therapy to preserve allograft function and decrease excessive complement activity.