Combination treatment of low dose Anti-Thymocyte Globulin (ATG), Rituximab and high dose Sirolimus as induction agents in immune-conditioned recipients.
A prospective study was performed to evaluate low dose Anti-Thymocyte Globulin (ATG) and Rituximab along with high dose Sirolimus as induction agents for reducing the incidence of acute rejection in renal transplantation. 66 patients who were to undergo live renal transplantation were divided into the low risk Group I (GpI, n=41) and the high risk Group II (GpII, n=25) recipients. Induction therapy included single dose Rituximab (200 mg), ATG (2 mg/kg) and Sirolimus 12 mg/d administered minus 3 days pretransplant. All patients underwent splenic radiation and Double Filtration Plasmapheresis (DFPP). Post-operatively, all recipients received MMF, prednisolone 5-10 mg/d and Tacrolimus started when serum creatinine (Scr) fell below 2.5 mg/dl on the first Post Operative Day (POD). If creatinine still remained high second dose ATG and Sirolimus continued. Once serum creatinine fell below 1.5 mg/dl Tacrolimus initiated at 0.1 mg per kg per day dose stopping ATG.


RESULTS
Acute rejection at 6 months for GpI was nil and for GpII it was 8%. Mean Scr on 1st POD was 1.8+/-0.6 mg/dl in GpI and 2.6+/-0.9 mg/dl in GpII. After 6 months the creatinine level in high risk was similar to that of low risk group (1.1+/-0.6 mg/dl in GpI and 1.2+/-0.8 mg/dl in GpII). No patient or graft loss was observed. Infections requiring hospitalization were observed in six patients and wound related complications requiring surgical intervention were observed in 4 of the 66 recipients.


CONCLUSIONS
Low dose ATG with Rituximab and high dose Sirolimus can be used as induction agents in immune-conditioned recipients with better apparent results than using high dose induction ATG. This combinational regimen also helps in individualizing post-operative immunosuppressive drugs based upon the post-operative renal function.
Ravichandran
Palani
P
Kidney Diseases and Institute of Organ Transplantation, St Thomas Hospital, Chennai, India. ravirekha@hotmail.com <ravirekha@hotmail.com>
Natrajan
T
T
Jaganathan
R
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007239:Infections / Q000209:etiology; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011446:Prospective Studies; D000069283:Rituximab; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000961:Antilymphocyte Serum; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003404:Creatinine; D020123:Sirolimus