Rituximab therapy for de novo mixed cryoglobulinemia in renal transplant patients

Background. Type 11 or III cryoglobulins are fairly prevalent in renal-transplant (RT) patients, and are often related to chronic hepatitis C virus (HCV) infection. However, they rarely result in graft dysfunction. They are sustained by proliferation of oligoclonal B-cells. Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have been achieved in HCV-positive immunocompetent patients with a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (i.e., rituximab). Thus, this provides the rationale to use rituximab for cryoglobulin-related graft dysfunction in RT patients. Methods. Three RT patients, of whom one was HCV-positive, developed renal-function impairment long after transplantation, as well as de novo nephrotic syndrome (n = 2) and severe hypertension (n = 2). This latter case was related to type III cryoglobulinemia and was associated with membranoproliferative glomerulonephritis. In addition to their baseline standard immunosuppression, the patients were given weekly rituximab infusions of 375 mg/m(2) (two infusions in patient and four infusions for the other two cases). Results. This treatment resulted in a dramatic improvement in renal parameters, particularly in a sustained remittence of nephrotic syndrome, a sustained clearance of cryoglobulins in two cases, but also in severe infectious complications in two cases. Conclusion. We conclude that rituximab therapy is highly effective in cryoglobulin-related renal dysfunction in RT patients; however, due to chronic immunosuppression, this is at the expense of infectious complications.