Effect of rapamycin on renal allograft survival in canine recipients treated with antilymphocyte serum, donor bone marrow, and cyclosporine.
Rapamycin (Rapa) monotherapy can promote renal allograft survival in dogs, but it is very toxic. To attempt to augment the effectiveness of Rapa and reduce its toxicity in a tolerance induction protocol, canine renal allograft recipients were treated briefly with antilymphocyte serum (ALS), donor bone marrow cells (BMC), and a limited course of cyclosporine (CsA). Rapa had little effect when CsA-treated recipients were given ALS on days -5 to -1 and BMC on day +1. When combined with CsA given days +13 to +42, ALS on days -5 to +7, and BMC on day +10, Rapa at 0.3 mg/kg on day +8 plus alternate days +15 to +39 significantly increased overall survival and was compatible with long-term survival after immunosuppression (6 grafts, 1 graft > 212 days, 1 graft > 470 days). Rapa appeared to prevent early rejections that can occur during treatment with these ALS/BMC/CsA protocols. Little toxicity of Rapa was observed with any treatment.
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
W C
WC
Hartner
W J
WJ
Van der Werf
J P
JP
Lodge
B
B
Gilchrist
S R
SR
De Fazio
T G
TG
Markees
C
C
Yatko
A P
AP
Monaco
J J
JJ
Gozzo
D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001853:Bone Marrow / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage; D004285:Dogs; D006085:Graft Survival / Q000187:drug effects*; D007114:Immunization; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000276:immunology*; D011090:Polyenes / Q000008:administration & dosage* / Q000009:adverse effects; D020123:Sirolimus; D014019:Tissue Donors
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D011090:Polyenes; D016572:Cyclosporine; D020123:Sirolimus