Study 1: effect of type of immunosuppression reduction in patients with BK allograft nephropathy

Abstract

O verimmunosuppression is a risk factor for BKAN virus allograft nephropathy. An ideal protocol for reduction in immunosuppression is needed to minimize the impact of this infection. In this study, 93 patients with BKAN were followed up for a mean of 16.8 months after the reduction in immunosuppression. Maintenance immunosuppression consisted of tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone in 86 patients; cyclosporine (CsA), MMF, and prednisone in 5 patients; and azathioprine, prednisone, and TAC or CsA in 2 patients. Protocols for reduction of immunosuppression were as follows: 37 patients received a calcineurin inhibitor (TAC, n 35; CsA, n 2) with MMF at 50% of the initial dose and prednisone. The target levels for TAC and CsA were 6 to 8 ng/mL and 75 to 100 mg/mL, respectively. A calcineurin inhibitor with prednisone was given to 29 patients (TAC, n 25 [18 low dose]; CsA, n 4 [3 low dose]). Twenty-seven patients received sirolimus (SRL)– based immunosuppression, 5 patients received SRL in combination with MMF (50% dose in 2 patients) and prednisone, and 2 patients received SRL in combination with a reduced dose of TAC and prednisone. The remaining 20 patients received only SRL and prednisone. Two patients received only MMF at 50% of initial dose and prednisone; 1 received only prednisone. After reduction of immunosuppression, biopsy-proven acute allograft rejection developed in 26% of patients. During the observation period, 26 patients (28%) lost graft function and in 21 patients (22.5%) the infection was cleared in subsequent biopsies and urine cytologic tests. There was no difference in the rate of acute allograft rejection between the immunosuppression reduction protocols. For patients in whom immunosuppression was reduced, those treated with prednisone and 2 immunosuppressant drugs (TAC, CsA or SRL, and MMF) were compared with patients receiving prednisone and a single immunosuppressant drug (TAC, CsA, SRL, or MMF). A significantly larger number of patients lost graft function in the first group (P .01). More significant graft loss was identified when patients received a calcineurin inhibitor (TAC or CsA) together with MMF and prednisone when compared with patients who received a single drug (TAC, CsA, SRL, or MMF) and prednisone (P .0017). Interestingly, disappearance of BK viral cytopathic changes in subsequent biopsies and urine samples was significantly higher in patients who received a single drug in addition to prednisone in comparison with patients who received 2 drugs and prednisone (P .009). Conclusion: Patients who were treated with a combination of prednisone and 1 other immunosuppressive agent had a much better graft survival and a higher chance of clearing the BK viruria compared with patients who were left on a regimen of 3 immunosuppressive drugs, albeit at lower doses. From the Departments of Medicine, Division of Nephrology, and Pathology, University of Maryland School of Medicine, Baltimore, MD. © 2003 Elsevier Inc. All rights reserved. 0955-470X/03/1704-0001$30.00/0 doi:10.1016/j.trre.2003.10.018