Study of Rituximab to Treat Chronic Renal Transplant Rejection

Purpose of clinical trial; Evaluate the effectiveness of rituximab in C4d+ CAN Primary objective; To determine whether anti-CD20 therapy can stabilize or improve renal function and/or proteinuria in patients with C4d+, chronic (humoral) rejection in whom standard therapeutic approaches have failed. Secondary objective (s); * To compare patient and graft survival between control and rituximab-treated groups * To evaluate the adverse effect profile of rituximab in this group * To correlate changes in circulating B cell numbers, anti-HLA and non-HLA Ab profiles and titre with responses to standard therapy and / or rituximab * To correlate changes in T cell responsiveness to alloantigens with responses to standard therapy and / or rituximab Study Design; Prospective, randomised, two arm, open-labeled Study Endpoints; Primary * Rate of deterioration in renal function, defined by slope of reciprocal creatinine plot, on samples taken 3-5 months post-randomisation. * Change in degree of proteinuria, where present, at 3-5 months post-randomisation 2˚ endpoints, determined at 3-5 months post-randomisation and at 1, 2 and 3 years post-recruitment are; * Rate of deterioration in renal function, defined by slope of reciprocal creatinine plot, determined by analysis of samples taken since previous assessment. * Patient survival * Graft survival * Incidence of culture positive infection * Incidence of malignancy * Degree of proteinuria * Changes in circulating CD20+ cells in peripheral blood * Changes in anti-graft Ab titres, (measured every 3 months) * Changes in T cell responsiveness to alloantigens (measured every 3 months). Sample Size; 15 patients to be randomised to each arm (i.e. 30 patients randomised). Up to 120 patients will need to be enrolled into the study. In addition, in those participants that received a living donor kidney, these donors will be approached to provide up to 5 samples of blood to help with the in vitro analyses. Summary of eligibility criteri