Inferior results with basis immunosuppression with sirolimus in kidney transplantation.
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.


CONCLUSIONS
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.
van den Akker
J M
JM
Department of Internal Medicine, Division of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
Hené
R J
RJ
Hoitsma
A J
AJ
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011239:Prednisolone; D000077561:Daclizumab; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus