Effectiveness of rituximab and intravenous immunoglobulin therapy in renal transplant recipients with chronic active antibody-mediated rejection.

BACKGROUND: Chronic active antibody-mediated rejection (CAMR) is an important cause of chronic kidney allograft dysfunction, but there has been no effective treatment protocol established for it.
METHODS: Six renal transplant recipients who showed progressive deterioration in graft function and CAMR as diagnosed by biopsy were enrolled. We administered a single dose of rituximab (375 mg/m(2)), followed by intravenous immunoglobulin (IVIg, 0.4 g/kg) for 4 days. The efficacy of this protocol was assessed on the basis of the improvement in allograft function, the amount of proteinuria, and the change in donor-specific antibodies (DSAs). We categorized the patients into 2 groups, responders and nonresponders, according to their response to the treatment.
RESULTS: All of the patients showed progressive deterioration of graft function before the diagnosis of CAMR. Luminex solid-phase assays showed that 3 patients had DSAs. After the treatment, allograft function improved or stabilized in 3 patients in the responder group, but still showed a deteriorating pattern in the nonresponder group. In the responder group, the amount of proteinuria also decreased after the treatment, but it increased in the nonresponder group. On diagnosis of CAMR, the nonresponders showed a longer posttransplantation period, a higher degree of transplant glomerulopathy, more severely deteriorated allograft function, and higher proteinuria compared with the responders.
CONCLUSIONS: The combination of rituximab and IVIg was effective in early-stage CAMR, but the effect was limited in the advanced stage.