Eculizumab in Pediatric Dense Deposit Disease

Abstract

Background and objectives Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children.Design, setting, participants, & measurements The authors analyzed clinical and histologic data of five pediatric patients with a native kidney biopsy diagnosis of DDD. Patients received eculizumab as therapy of last resort for severe nephritic or nephrotic syndrome with alternative pathway complement activation; this therapy was given only when the patients had not or only marginally responded to immunosuppressive therapy. Outcome measures were kidney function, proteinuria, and urine analysis.Results In all, seven disease episodes were treated with eculizumab (six episodes of severe nephritic syndrome [two of which required dialysis] and one nephrotic syndrome episode). Median age at treatment start was 8.4 (range, 5.9-13) years. For three treatment episodes, eculizumab was the sole immunosuppressive treatment. In all patients, both proteinuria and renal function improved significantly within 12 weeks of treatment (median urinary protein-to-creatinine ratio of 8.5 [range, 2.2-17] versus 1.1 [range, 0.2-2.0] g/g, P,0.005, and eGFR of 58 [range, 17-114] versus 77 [range, 50-129] ml/min per 1.73 m 2 , P,0.01). A striking finding was the disappearance of leukocyturia within 1 week after the first eculizumab dose in all five episodes with leukocyturia at treatment initiation.Conclusions In this case series of pediatric patients with DDD, eculizumab treatment was associated with reduction in proteinuria and increase in eGFR. Leukocyturia resolved within 1 week of initiation of eculizumab treatment. These results underscore the need for a randomized trial of eculizumab in DDD.

C3 glomerulopathy in children: Is there still a place for anti‐cellular immunosuppression?

“…Six patients (23%) had global clinical response, 6 (23%) had partial and 14 had (54%) NR. On the other hand, Oosterveld et al . reported five paediatric dense‐deposit disease patients who all improved (both proteinuria and renal function) significantly within 12 weeks of eculizumab treatment.…”

“…Six patients (23%) had global clinical response, 6 (23%) had partial and 14 had (54%) NR. On the other hand, Oosterveld et al 22 reported five paediatric densedeposit disease patients who all improved (both proteinuria and renal function) significantly within 12 weeks of eculizumab treatment. Taking case reports and larger series all together, our results with eculizumab in C3GP patients are quite in concordance with them, meaning that the success of eculizumab in C3GP is not universal and not 100% in all patients.…”

“…In the majority of case reports published, clinical improvement with eculizumab was, however, reported, but can be said to be biased by reporting mostly positive results. On the other hand, a closer look at, though very few (especially in children), large series of eculizumab‐treated C3GP patients describe various results …”

“…On the other hand, a closer look at, though very few (especially in children), large series of eculizumab-treated C3GP patients describe various results. [19][20][21][22] The prognosis of C3GP is relatively unfavourable. Recurrence in transplanted kidneys is also possible.…”

Histopathological findings in transplanted kidneys

“…A few patients may respond to plasma exchange [169]. Good results have been reported with eculizumab in DDD patients [170,171]. Fourteen of 21 (66.7%) patients with C3GN developed recurrence at 28 months (median) after transplantation.…”