Sirolimus (rapamycin)-based therapy in human renal transplantation -: Similar efficacy and different toxicity compared with cyclosporine

被引:727
|
作者
Groth, CG [12 ]
Bäckman, L
Morales, JM
Calne, R
Kreis, H
Lang, P
Touraine, JL
Claesson, K
Campistol, JM
Durand, D
Wramner, L
Brattström, C
Charpentier, B
机构
[1] Karolinska Inst, Huddinge Hosp, S-10401 Stockholm, Sweden
[2] Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden
[3] Hosp 12 Octubre, E-28041 Madrid, Spain
[4] Addenbrookes Hosp, Cambridge, England
[5] Hop Necker Enfants Malad, Paris, France
[6] Hop Henri Mondor, F-94010 Creteil, France
[7] Hop Edouard Herriot, Lyon, France
[8] Univ Uppsala Hosp, Uppsala, Sweden
[9] Hosp Clin Barcelona, Barcelona, Spain
[10] Univ Hosp Rangueil, Toulouse, France
[11] Hop Bicetre, Kremlin Bicetre, France
[12] Huddinge Hosp, Dept Transplant Surg, S-14186 Huddinge, Sweden
关键词
D O I
10.1097/00007890-199904150-00017
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background Sirolimus (rapamycin) is a potent immunosuppressant with a mechanism of action different from cyclosporine (CsA) or tacrolimus. Methods. In 11 European centers, first cadaveric renal allograft recipients were randomized to CsA (n=42) or sirolimus (n=41). Dosing of these agents was concentration-controlled and open-labeled. All patients received corticosteroids and azathioprine. Results. At 12 months, graft survival (98% sirolimus vs. 90% CsA), patient survival (100% vs. 98%), and incidence of biopsy-confirmed acute rejection (41% vs. 38%) were similar, Serum creatinine was lower with sirolimus, significantly (P less than or equal to 0.05) so at 3 and 4 months, and serum uric acid and magnesium were normal. Laboratory abnormalities reported significantly more often with sirolimus included hypertriglyceridemia (51% vs. 12%), hypercholesterolemia (44% vs. 14%), thrombocytopenia (37% vs, 0%), leukopenia (39% vs. 14%), and, of lesser importance, increased liver enzymes and hypokalemia. These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/ml. Occurrence of cytomegalovirus was comparable (14% vs. 12%); incidences of herpes simplex (24% vs. 10%, P=0.08) and pneumonia (17% vs. 2%, P=0.03) were higher with sirolimus. No gingival hyperplasia was seen with sirolimus, tremor was rare, and hypertension was less frequent (17% vs. 33%), Two malignancies were observed with CsA and none with sirolimus. Conclusions. Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection, and has a safety profile that differs from CsA.
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收藏
页码:1036 / 1042
页数:7
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