Rabbit anti-human thymocyte immunoglobulin for the rescue treatment of chronic antibody-mediated rejection after pediatric kidney transplantation

• Published in: Pediatric nephrology (Berlin, West) West), 2017-11, Vol.32 (11), p.2133-2142
• Main Authors: Cihan, Yasemen, Kanzelmeyer, Nele, Drube, Jens, Kreuzer, Martin, Lerch, Christian, Hennies, Imke, Froede, Kerstin, Verboom, Murielle, Ahlenstiel-Grunow, Thurid, Pape, Lars
• Format: Article
• Language: English
• Subjects: Adolescent; Animals; Antibodies; Antilymphocyte Serum - therapeutic use; Bortezomib; Bortezomib - therapeutic use; Child, Preschool; Chronic Disease; Complications and side effects; Data processing; Epidermal growth factor receptors; Female; Glomerular Filtration Rate; Graft rejection; Graft Rejection - drug therapy; Graft Rejection - immunology; Graft Survival; Health aspects; Histocompatibility antigen HLA; Humans; Hypersensitivity; Immunoglobulins; Immunoglobulins, Intravenous - therapeutic use; Immunosuppression; Immunosuppressive Agents - therapeutic use; Intravenous administration; Kidney - immunology; Kidney - pathology; Kidney - surgery; Kidney transplantation; Kidney Transplantation - adverse effects; Kidney transplants; Leukopenia; Male; Medicine; Medicine & Public Health; Monoclonal antibodies; Nephrology; Original Article; Pediatric surgery; Pediatrics; Prednisolone; Prednisolone - therapeutic use; Prevention; Rabbits; Retrospective Studies; Rituximab; Rituximab - therapeutic use; Transplantation; Transplants & implants; Treatment Outcome; Urology
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-017-3725-1

Background Chronic antibody-mediated rejection (cAMR) is the leading cause of late kidney graft loss, but current therapies are often ineffective. Rabbit anti-human thymocyte immunoglobulin (rATG) may be helpful, but its use is virtually undocumented. Methods Data were analyzed retrospectively from nine pediatric kidney transplant patients with cAMR were treated with rATG (1.5 mg/kg × 5 days) at our center after non-response to pulsed prednisolone, intravenous immunoglobulin, rituximab, and increased immunosuppressive intensity (including switching to belatacept in some cases), with or without bortezomib. Results The median time from diagnosis to cAMR was 179 days. rATG was started 5–741 days after diagnosis. Median estimated glomerular filtration rate (eGFR) increased from 40 mL/min/1.73 m 2 when rATG was started to 62 mL/min/1.73 m 2 9 months later ( p  = 0.039). Four patients showed substantially higher eGFR after 9 months and 2 patients showed a small improvement; eGFR continued to decline in 3 patients after starting rATG. No grafts were lost during follow-up. At last follow-up, donor-specific antibodies (DSAs) were no longer detectable in 4 out of 8 patients for whom data were available, median fluorescence intensity had decreased substantially in 1 out of 8 patients; anti-HLA DQ DSAs persisted in 2 out of 8 patients. No adverse events with a suspected relation to rATG, including allergic reactions, leukocytopenia or infections, were observed in any of the patients. Conclusions In this small series of patients, rATG appears a promising treatment for unresponsive cAMR. Further evaluation, including earlier introduction of rATG, is warranted.