Introduction: There is a lack of high-quality evidence for treatment of antibody-mediated rejection (AMR) in pediatric kidney transplantation. Recent clinical trials in adult recipients show promising effectiveness targeting CD38 to inhibit graft injury. However, their safety and effectiveness in pediatric patients remains unexplored.
Methods: We report two pediatric cases of AMR treated with the Anti-CD38 antibody Daratumumab. Case 1 was a 14-year-old girl with chronic kidney disease of unknown cause with a deceased donor kidney transplant (CMV D-/R+, EBV D+/R-). Her post-transplant course was complicated by post-transplant diabetes and recurring T cell-mediated rejections due to non-adherence. 2.5 years post-transplant she developed acute AMR with graft dysfunction (eGFR 30 ml/min/1,73m2) and donor-specific antibodies (DSAs). She was treated with 5 plasmapheresis sessions, high-dose methylprednisolone pulses, intravenous immunoglobulins (IVIG), and 4 doses of Daratumumab given weekly. Maintenance IVIG therapy continued every four weeks. Case 2, a 16-year-old girl with a complex urological and transplant history (cloacal malformation, second kidney transplant, deceased donor, CMV D+/R+, EBV D unknown/R-), presented with acute kidney injury 2 years post-transplant (eGFR 11 ml/min/1.73m²).  Biopsy confirmed diagnosis of AMR with significant DSA elevation. Daratumumab treatment was initiated at a total of 4 doses alongside methylprednisolone pulses and followed by maintenance IVIG.
Results: In case 1, Daratumumab led to histological remission of AMR, but graft function progressively declined, with nearly complete tubular atrophy. In case 2, graft function was normalized to pre-rejection levels. Other than mild infusion reactions, no immediate side effects were present. However, in both cases asymptomatic CMV reactivation occurred (in case 1 after 4 doses, in case 2 after two doses of Daratumumab) and was successfully managed with Valganciclovir and MMF reduction. In addition, one patient developed shingles, treated with acyclovir, while the other developed BK viremia. Due to these adverse effects and signs of AMR remission Daratumumab was discontinued in favor of monthly IVIG. In case 1 a follow-up biopsy five months post-treatment showed no active AMR, in case 2 DSA levels declined but persisted but graft function remained stable over the following year.
Conclusions: In both cases, Daratumumab combined with steroid pulses (and in case 1 with plasmapheresis) effectively controlled AMR. In case 1, however, it did not halt graft deterioration. Contrasting current adult evidence, viral reactivation following CD38 inhibition may be more prevalent in pediatric populations, underlining the importance of risk-based antiviral prophylaxis (e.g., CMV, VZV). These cases support existing evidence on the efficacy of Daratumumab for AMR and emphasize the need for vigilant monitoring of treatment-related side effects.