Acute Antibody-Mediated Rejection and its Treatment in Kidney Transplantation: Report from a National Cohort Study
Nancy Perrottet1, Dela Golshayan2, Samuel Rotman3, Solange Moll4, Helmut Hopfer5, Emmanuelle Catana2, Michael Koller6, Jean-Pierre Venetz2, Vincent Aubert7, Julien Vionnet2, Oriol Manuel2,8, Léo Bühler9, Karin Hadaya10, Thomas Mueller11, Uyen Huynh-Do12, Isabelle Binet13, Michael Dickenmann14, Juerg Steiger14, Manuel Pascual2.
1Service of Pharmacy, University Hospital (CHUV), Lausanne, Switzerland; 2Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland; 3Pathology Institute, University Hospital (CHUV), Lausanne, Switzerland; 4Division of Clinical Pathology, Department of Pathology and Immunology, Geneva University Hospital and Medical School, Geneva, Switzerland; 5Pathology Institute, University Hospital Basel, Basel, Switzerland; 6Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland; 7Service of Immunology, University Hospital (CHUV), Lausanne, Switzerland; 8Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland; 9Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, Geneva, Switzerland; 10Division of Nephrology and Division of Transplantation, Geneva University Hospitals, Geneva, Switzerland; 11Division of Nephrology, University Hospital Zurich, Zurich, Switzerland; 12Division of Nephrology, Hypertension and Clinical Pharmacology, Inselspital Bern, Bern, Switzerland; 13Nephrology and Transplantation Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland; 14Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
Swiss Transplant Cohort Study (STCS).
Background: The management of antibody mediated rejection (AMR) remains nowadays a major challenge in kidney transplantation. Different therapeutic strategies are used but more data are needed to define the optimal treatment. This is the first report of the treatment of acute AMR in kidney transplant recipients in a real-life multicenter cohort study setting.
Methods: Kidney transplant recipients (May 2008 – 2014) who received a treatment for an acute AMR episode occurring in the first year posttransplantation (post-Tx) were included from the Swiss Transplant Cohort (STCS). The main objectives were to describe the treatment used and to analyze the outcomes in term of efficacy (serum creatinine at 3 months post-acute AMR) and safety (incidence of infectious complications within 6 months post-acute AMR).
Results: Overall, 64/1669 (3.8%) patients were treated for an acute AMR occurring in the first year post-Tx (74 episodes in total). In addition to corticosteroid boluses, the most common treatment modalities used were Plasma exchange or pheresis (55.4%) and IVIG (39.2%) followed by rituximab (25.7%) and antithymocytes globulins (23.0%), and finally eculizumab (4.1%) and bortezomid (4.1%). Most acute AMR were managed with bitherapy (43.2% of episodes), mostly corticosteroids and plasmapheresis, but as much as 5 therapies were used in combination in few patients (n=4). At 3 months post-rejection, the treatments used were overall effective with a full recovery of allograft function in 67.6% of the cases. In patients with de novo DSA (n=7), this proportion reached 85.7% compared to 56.0% in patients with preformed DSA (n=50) (not significant). The graft loss at 1-year was 9.2% (6/65), the majority related to ongoing rejection. At 12 months post-Tx, 33.3% of the patients cleared all DSA (11/33). In patients with de novo DSA (n=7), the clearance reached 71.4%, compared to 23.8% in patients with preformed DSA (n=21) (p=0.02). The treatments of acute AMR were followed by at least one infectious complication in the following 6 months in 63.6% of cases. The overall incidence of viral infections was 71.2% (47/66), with 13.6% of CMV diseases and 7.6% of BK viremia. The bacterial and fungal infectious complications reached 43.9% and 7.6% respectively. At 1-year, patient survival was 93.7%. Two patients died due to severe infectious complications (3.1%).
Conclusions: In this multicenter national cohort study, we found a wide variety of therapeutic strategies used to treat acute AMR, supporting the need for more controlled trials in the management of acute AMR. Despite this heterogeneity in the treatments used, the graft survival at 1-year reached 91%, with an overall good response to therapy at 3 months. However, infectious complications were common, including severe infections rarely leading to patient loss.
