Rituximab as Treatment for Refractory Kidney Transplant Rejection

Abstract

Recent studies have shown that a high density of CD 20+ cells are seen in patients who have steroid-resistant rejection episodes. Rituximab is a high-affinity CD-20 specific antibody that inhibits B-cell proliferation while inducing cellular apoptosis. Thus, it is a rational choice for therapy in transplantation to abrogate B-cell-mediated events. Twenty-seven patients were diagnosed with biopsy-confirmed rejection manifested by thrombotic microangiopathy and/or endothelialitis between 2/99 and 2/02 at our institution. These individuals were treated with a single dose of rituximab, in addition to other therapies, in an effort to reverse their rejection episodes. Twenty-four received additional steroids while 22 of the 27 patients were also treated with plasmapheresis and antithymocyte globulin (ATG). Only three patients experienced graft loss not associated with patient death during the follow-up period (605 +/- 335.3 days). In the 24 successfully treated patients, the serum creatinine at the time of initiating rituximab therapy was 5.6 +/- 1.0 mg/dL and decreased to 0.95 +/- 0.7 mg/dL at discharge. The addition of rituximab may improve outcomes in severe, steroid-resistant or antibody-mediated rejection episodes after kidney transplantation.

Successful Treatment of Refractory Acute Humoral Allograft Rejection with Single Dose Rituximab

“…Some of these antibodymediated rejection episodes are refractory to conventional treatments. Becker et al fi rst reported successful treatment of such a steroid-resistant rejection episode with rituximab (6). Since then a number of case series and reports have been published with regards to success of rituximab in this particular indication (4,6).…”

“…Becker et al fi rst reported successful treatment of such a steroid-resistant rejection episode with rituximab (6). Since then a number of case series and reports have been published with regards to success of rituximab in this particular indication (4,6). Rituximab is a chimeric murine/human anti CD 20 antibody which directly inhibits B cell proliferation by antibody-dependent, cell-mediated, and complement-mediated cytotoxicity (7).…”

Prolonged Symptoms in Solid Organ Transplant Recipients with Enteroviral Meningitis

“…Thus, enteroviral infections may not occur with increased frequency in most populations of SOT recipients compared to normal hosts. However, as more biologic agents with B cell depleting properties, such as alemtuzumab and rituximab are being used in patients with solid organ transplant for induction of immunosuppression and therapy for rejection [16,17], it may be that these infections will be encountered more frequently or that more severe infections may occur.…”

Antibody immunosuppressive therapy in solid organ transplant

“…In 2004, Becker et al reported that single-dose rituximab reversed steroid-refractory kidney rejection episodes in 24 of 27 patients. 23 Shortly thereafter, Genberg et al showed…”