Background: The introduction of sirolimus has provided
the opportunity to develop an immunosuppressive regimen without the nephrotoxic calcineurin inhibitors.
Methods: We conducted a first trial in 30 renal allograft
recipients. Ten patients were followed prospectively and
received sirolimus, to achieve a target blood level of 10 to 15 ng/ml, induction therapy with one dose of daclizumab, low-dose steroids and mycophenolate mofetil. We compared this group with a historical control group of 20 patients who received our standard treatment consisting of tacrolimus, low-dose steroids, and mycophenolate mofetil.
Results: After a mean follow-up of 15 weeks, seven patients developed an acute rejection in the sirolimus group (70%) compared with three patients in the tacrolimus group (15%) (p<0.01). Because of this unacceptable high rate of acute rejections we conducted a second prospective pilot study in nine patients. These patients received sirolimus in combination with two doses of daclizumab, high-dose steroids and mycophenolate mofetil. No rejections occurred under this
immunosuppressive regimen; however, many immunosuppression-related adverse events were seen.
Conclusion: The present study demonstrates an
unacceptably high rate of acute rejections (70%) in patients treated with sirolimus, daclizumab, mycophenolate mofetil and low-dose prednisolone. No rejections but many adverse
events were seen when sirolimus was given in combination with high-dose steroids.