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USE OF ANTI-C5 ANTIBODY TO TREAT A PLASMAPHERESIS-RESISTANT ACUTE HUMORAL REJECTION IN A PEDIATRIC KIDNEY RECIPIENT

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Abstract

INTRODUCTION. Even if kidney graft survival has improved during the last decades, highly immunized paediatric waitlisted patients are an emerging problem.

METHODS. We describe a caucasian 17-year-old male, transplanted at 3 years of age, who lost his graft due to chronic allograft nephropathy. While on the waiting list he presented a rise in Panel Reactive Antibodies levels (PRA99.61%); he received a desensitization protocol based on plasmapheresis (PP), immunoglobulins and Rituximab with minor response (post-desensitization PRA75%). He was enrolled in a National Protocol for organs allocation to highly sensitized patients and received his second non-living HLA-compatible transplant at the age of 16. His graft recovered promptly and serum creatinine fell to 1mg/dL after one month. On postoperative-day 30 he developed a biopsy-proven antibody-mediated rejection (AMR) (max creatinine 2mg/dL). Post-transplant immunological monitoring showed donor-specific anti-DQ5 antibodies (DSA) that were already present at the time of transplantation (MFI 20.000). He received methylprednisolone pulses and 45 PP-sessions, starting with daily sessions gradually reduced to twice/week. A stabilization of creatinine levels (1.5mg/dL) was observed, but a raise in creatinine and DSA levels occurred after PP’s frequency reduction. PP sessions were then enhanced and a drop in creatinine levels was observed. A second graft biopsy demonstrated a persistent C4d positive humoral rejection. Therefore, considering the PP-resistant AMR, the option of receiving Eculizumab, an anti-C5 antibody, was offered. Eculizumab was administered starting with two weekly infusions, followed by two infusions every two weeks; PP was discontinued.

RESULTS AND CONCLUSIONS. After the fourth Eculizumab infusion graft function was normal and a third biopsy showed the resolution of AMR although DSA-title rose after PP-discontinuation and C4d immunostaining persisted positive. Taking into account graft function stabilization and the improved histological features Eculizumab infusions were continued.

Eculizumab allowed our patient to stop PP-therapy; one year after transplantation, in a monthly Eculizumab infusion regimen, graft function is stable (creatinine 1.2mg/dL). Anti-C5 therapy may represent an effective therapeutic option also in pediatric patients with PP-resistant AMR.

G. Ghirardo(1), E. Benetti(1), F. Poli(2), E. Vidal(1), E. Cozzi(3), L. Murer(1)
((1)S.s. Nefrologia Pediatrica, Dialisi E Trapianto - Dipartimento Di Pediatria Salus Pueri Padova , (2)Ircss Fondazione Ca Granda, Ospedale Maggiore Policlinico Milano , (3)U.o.s. Immunologia Clinica E Sperimentale Dei Trapianti, Azienda Ospedaliera Padova )
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Realizzazione: Tesi S.p.A.

Per assistenza contattare: Claudia Ingrassia, Tesi S.p.A.
0172 476301 — claudia.ingrassia@gruppotesi.com