WITHDRAWAL OF CYCLOSPORINE OR PREDNISONE IN RENAL TRANSPLANT RECIPIENTS TREATED WITH MYCOPHENOLATE MOFETIL, CYCLOSPORINE, AND PREDNISONE: A RANDOMISED STUDY.

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WITHDRAWAL OF CYCLOSPORINE OR PREDNISONE IN RENAL TRANSPLANT RECIPIENTS TREATED WITH MYCOPHENOLATE MOFETIL, CYCLOSPORINE, AND PREDNISONE: A RANDOMISED STUDY.

The addition of mycophenolate mofetil (MMF) to cyclosporine (CsA) and prednisone (Pred) has reduced the rate of biopsy-proven acute rejections in the first six months after renal transplantation (RTx) by nearly 50%. It is unknown however, which is the optimal immunosuppressive regimen from 6 months after RTx, in patients on triple therapy with MMF. We performed a randomised trial, in which Pred or CsA were withdrawn six months after RTx, in order to avoid the potential risks of over-immunosuppression.

Methods: In this multicentre study, renal transplant recipients treated with MMF, Pred, and CsA were randomised at six months after RTx to (1) stop CsA, (2) stop Pred or (3) continue triple therapy. The MMF dose was 1000 mg bid and target whole blood trough levels of CsA were 150 ng/mL. The Pred dose was 0.10 mg/kg/day; in patients discontinuing CsA, the Pred dose was increased to 0.15 mg/kg/day. Data regarding the first six months after randomisation were analysed.

Results: 94 patients were included: 30 in the MMF/Pred group, 34 in the MMF/CsA group and 30 in the MMF/CsA/Pred group. Patients with an unstable graft function and patients with two or more acute rejections within the first six months after transplantation were excluded. At randomisation, there were no differences between the groups in graft function, CsA dose and level, or rejection incidence before randomisation. Withdrawal of CsA was followed by an acute rejection in 6/30 patients while no rejection occurred in the other two groups (P=0.001). Rejections were steroid resistant in 2/6 patients; in 3/6 patients CsA was restarted. No graft loss or patient death occurred. During follow-up, no significant changes occurred in graft function, number of antihypertensive drugs or CsA levels within each group, nor were there any differences between the groups regarding these parameters.

Conclusion: In stable renal transplant patients treated with the combination of MMF, CsA and Pred, Pred can be safely withdrawn but withdrawal of CsA results in a rejection incidence of 20%, with 33% of these rejections being steroid-resistant.

This study was funded in part by Roche, Mijdrecht, the Netherlands

RGL de Sévaux ⁽¹⁾, PJH Smak Gregoor ⁽²⁾, RJ Hené⁽³⁾, W Weimar⁽²⁾, AJ Hoitsma⁽¹⁾, G. Ligtenberg ⁽³⁾, T van Gelder⁽²⁾, LB Hilbrands ⁽¹⁾. Depts of Nephrology, University Hospitals of Nijmegen ⁽¹⁾, Rotterdam⁽²⁾ and Utrecht ⁽³⁾, The Netherlands

WITHDRAWAL OF CYCLOSPORINE OR PREDNISONE IN RENAL TRANSPLANT RECIPIENTS TREATED WITH MYCOPHENOLATE MOFETIL, CYCLOSPORINE, AND PREDNISONE: A RANDOMISED STUDY.

RGL de Sévaux (1), PJH Smak Gregoor (2), RJ Hené (3), W Weimar (2), AJ Hoitsma (1), G. Ligtenberg (3), T van Gelder (2), LB Hilbrands (1). Depts of Nephrology, University Hospitals of Nijmegen (1), Rotterdam (2) and Utrecht (3), The Netherlands

RGL de Sévaux ⁽¹⁾, PJH Smak Gregoor ⁽²⁾, RJ Hené⁽³⁾, W Weimar⁽²⁾, AJ Hoitsma⁽¹⁾, G. Ligtenberg ⁽³⁾, T van Gelder⁽²⁾, LB Hilbrands ⁽¹⁾. Depts of Nephrology, University Hospitals of Nijmegen ⁽¹⁾, Rotterdam⁽²⁾ and Utrecht ⁽³⁾, The Netherlands