Effect of sirolimus in combination with low-dose cyclosporine and steroids on acute renal allograft rejection.
OBJECTIVE
Sirolimus is a novel immunosuppressive drug with much less nephrotoxicity than cyclosporine. The efficacy and toxicity of the combination of sirolimus and low-dose cyclosporine therapy were compared with data from records of a previous cyclosporine-based regimen used in patients with renal allograft transplantation.


METHODS
A prospective study was conducted to assess the clinical effects of a sirolimus (6 mg loading dose over 48 hours plus 2 mg/day maintenance)/cyclosporine (8 mg/kg/day) combination regimen. Three male and 9 female renal transplant recipients were enrolled in the study. The primary endpoint was the incidence of acute rejection. The efficacy and adverse effects of the combined therapy were compared with those recorded in medical records of 24 renal transplant recipients who had received a cyclosporine-based regimen (10 mg/kg/day).


RESULTS
The 12-month acute rejection rate of the study group was 16.67% (2/12), and that of the cyclosporine-based group 29.16% (7/24). One patient in the study group died of complications sustained during a radical operation for recurrent bladder carcinoma during the sixth post-transplant month. The 12-month graft and patient survival rates of the study group were both 91.8%. In the 12 months post-transplant, the mean serum creatinine levels of the study group were significantly lower than those of the historic group at months 1, 3, and 4. The average cyclosporine trough levels of the study group were significantly lower than those of the historic group at months 1, 2, and 12. The average daily doses of prednisolone in the study group were also lower than those of the historic group at months 2, 3, 4, and 12.


CONCLUSIONS
The sirolimus/cyclosporine combination regimen reduced the incidence of acute renal allograft rejection, did not affect renal function, and reduced the dosage of cyclosporine and steroids compared with the cyclosporine regimen.
Tsai
Meng-Kun
MK
Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Rd, Taipei 100, Taiwan.
Chueh
Shih-Chieh
SC
Hu
Rey-Heng
RH
Lee
Po-Huang
PH
D000208:Acute Disease; D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D008775:Methylprednisolone