Can We Eliminate Both Calcineurin Inhibitors and Steroids?

Calcineurin inhibitors (CNIs) and steroids, the cornerstone of most immunosuppressive regimens in the past 20 years, have undesirable chronic effects. This has led to the use of new strategies with sirolimus (SRL) and mycophenolate mofetil (MMF). In the SPIESSER study, de novo CNI avoidance and early steroid withdrawal were evaluated in 145 renal recipients randomized to receive either SRL (n = 71) or cyclosporine (CsA; n = 74). All patients received polyclonal antithymocyte globulin for 5 days, MMF, and steroids withdrawn at 6 months. At 12 months, the incidence of biopsy-proven acute rejection was low (14.3% for SRL vs 8.6% for CsA). At 3 years, renal function (Nankivell) was better in the SRL group, particularly in patients who remained on treatment according to the protocol (71 ± 22 vs 60 ± 17 mL/min; P < .01). Steroids were withdrawn in 70.5% of SRL-treated patients and in 66.7% of CsA-treated patients. In the CONCEPT study, early conversion from CsA to SRL was evaluated in 192 renal recipients prospectively randomized at week 12 to switch from CsA to SRL (n = 95) or to continue CsA (n = 97). At 12 months, estimated glomerular filtration rate (Modification of Diet in Renal Disease) was significantly higher with SRL (61 ± 16 vs 54 ± 15 mL/min; P = .002, intent-to-treat analysis). The significant improvement in renal function was maintained at 30 months. In both studies graft and patient survival were similar, with better renal function and a tendency for fewer cancers observed at follow-up in patients receiving a maintenance regimen with SRL and MMF. At 30 months, steroids had been withdrawn in 72% of SRL-treated patients and in 70% of CsA-treated patients.