Eculizumab as treatment in dense deposit disease in children

Abstract

Background: Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease that occurs secondary to hyperactivity of the alternative complement pathway. Renal biopsy typically reveals electron-dense deposits in the glomerular basement membrane. However, treatment options are limited. Till date, to the best of our knowledge, no evidence exists for specific treatment influencing the disease course. Eculizumab, a monoclonal antibody, has been reported to prevent membrane attack complex formation by binding to C5 and leads to improvement in clinical findings. However, the number of reported cases in which eculizumab was administered, particularly in children, is limited. Subjects and Methods: In this report, we present our experience with three pediatric cases of DDD receiving eculizumab treatment. All three patients were diagnosed with DDD on kidney biopsy. All patients showed acute kidney injury, high blood pressure, proteinuria >1 g/day, and decreased C3 levels. Immunosuppressive therapy, which included high-dose methylprednisolone, prednisolone, mycophenolate mofetil, or plasma exchange (in the third patient), as well as antihypertensive drugs, was administered to all the patients. Eculizumab treatment was initiated early in two patients but was initiated later in the third patient, who underwent dialysis initially. Results: The two patients with early initiation of eculizumab treatment showed significant improvement of proteinuria and renal function within weeks of treatment. C3 levels were normalized in one patient but remained decreased in the other. The third patient showed no response. She ultimately progressed to end-stage renal disease and eventually needed maintenance dialysis. Conclusions: Early initiation of eculizumab was associated with decreased proteinuria and improved renal function in two patients. These findings were in agreement with previous reports on the beneficial effects of eculizumab in DDD patients.