Treatment response to daratumumab in antibody-mediated kidney allograft rejection: evidence from serial protocol biopsies
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
ABSTRACT Background Antibody-mediated rejection (ABMR) is a major cause of chronic allograft dysfunction and graft loss after kidney transplantation (KTx). Daratumumab, antibody targeting the transmembrane glycoprotein CD38 (cluster of differentiation) on immune cells, has shown promise in the treatment of refractory ABMR in adult solid organ transplantation; however, pediatric data are scarce. abs1 Methods We report two pediatric cases of refractory ABMR after KTx treated with daratumumab with followed-up protocol biopsies over 10–12 months. Treatment consisted of an induction phase with five weekly doses followed by maintenance dosing every two to four weeks. Donor-specific antibodies (DSAs), kidney function, albuminuria, and histologic response were assessed. abs2 Results The first case, a 10-year-old girl with recurrent ABMR after KTx showed histologic improvement from active ABMR with C4d positivity, glomerulitis, and severe microvascular inflammation to predominantly chronic changes without signs of active rejection. Microvascular inflammation became mild and C4d staining turned negative. The second case, a 9-year-old boy with active and chronic antiglomerular basement membrane disease and severe transplant ABMR glomerulopathy initially showed progression of chronic injury, followed by complete histologic resolution of active disease, disappearance of C4d staining, minimal fibrosis (<1%), and marked reduction of albuminuria after 10 months. Both patients demonstrated re
Abstract
ABSTRACT Background Antibody-mediated rejection (ABMR) is a major cause of chronic allograft dysfunction and graft loss after kidney transplantation (KTx). Daratumumab, antibody targeting the transmembrane glycoprotein CD38 (cluster of differentiation) on immune cells, has shown promise in the treatment of refractory ABMR in adult solid organ transplantation; however, pediatric data are scarce. abs1 Methods We report two pediatric cases of refractory ABMR after KTx treated with daratumumab with followed-up protocol biopsies over 10–12 months. Treatment consisted of an induction phase with five weekly doses followed by maintenance dosing every two to four weeks. Donor-specific antibodies (DSAs), kidney function, albuminuria, and histologic response were assessed. abs2 Results The first case, a 10-year-old girl with recurrent ABMR after KTx showed histologic improvement from active ABMR with C4d positivity, glomerulitis, and severe microvascular inflammation to predominantly chronic changes without signs of active rejection. Microvascular inflammation became mild and C4d staining turned negative. The second case, a 9-year-old boy with active and chronic antiglomerular basement membrane disease and severe transplant ABMR glomerulopathy initially showed progression of chronic injury, followed by complete histologic resolution of active disease, disappearance of C4d staining, minimal fibrosis (<1%), and marked reduction of albuminuria after 10 months. Both patients demonstrated reduced DSA levels, stabilization of graft function, and no serious adverse events. abs3 Conclusion Daratumumab was associated with histologic improvement, reduction of microvascular inflammation, and stabilization of graft function in two children with refractory ABMR after KTx. Controlled studies to determine the safety, efficacy, and optimal dosage of daratumumab in children with ABMR are needed. abs4