title: Sirolimus monotherapy versus sirolimus in combination with steroids and/or MMF for immunosuppression after liver transplantation.
abstract: Calcineurin inhibitor (CI)-associated renal dysfunction has emerged as a major cause of morbidity and mortality after liver transplantation. In this retrospective study, we compared the efficacy, safety, and renal protective effect of sirolimus monotherapy (Group A; n = 26) with sirolimus in combination (Group B; n = 34) with steroids and/or mycophenolate mofetil (MMF) in liver transplant recipients who were switched from CI. Patients were switched abruptly or over a period of 2-4 weeks and followed for 17 +/- 10 months. Preconversion renal biopsies in five of six patients showed histological features consistent with CI nephrotoxicity. Serum creatinine increased in the year prior to conversion from 1.7 +/- 0.4 to 2.1 +/- 0.7 mg/dl (P = 0.009) and improved thereafter (1 month, 1.7 +/- 0.6, P < 0.001; 6 months, 1.6 +/- 0.5, P < 0.001; last follow-up, 1.7 +/- 0.9, P = 0.02); only four patients showed a significant decline in renal function after conversion. Seven (11.3%) patients experienced acute rejection (Group A, two; Group B, five; P = NS) and this resulted in the discontinuation of sirolimus in one patient. Fifty-four adverse events occurred in 40 (67%) patients, with similar numbers of adverse events in Group A and Group B. Most episodes of rejection (5/7; 71%), adverse events (45/54; 83%), and discontinuations (5/8; 63%) occurred within 6 months of conversion. We conclude that both sirolimus monotherapy and sirolimus in combination with prednisone and/or MMF are efficacious and safe in liver transplant recipients. Conversion to sirolimus was associated with an immediate improvement in renal function that was sustained during the follow-up.
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Anurag
authors.initials: A
authors.lastname: Maheshwari
authors.forename: Michael S
authors.initials: MS
authors.lastname: Torbenson
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thuluvath
mesh_terms: D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage*
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D020123:Sirolimus