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A Prospective, Multinational Pharmacoepidemiological Study of Clinical Conversion to Sirolimus Immunosuppression after Renal Transplantation

This prospective pharmacoepidemiological study examined treatment and outcomes in patients converted to sirolimus (SRL) after renal transplantation. 484 subjects in 36 centres in 7 countries were followed for up to 5 years. Principal reasons for conversion were declining graft function (146/484, 30%) and side effects of prior therapy (144/484, 30%) and the major treatment combinations after conversion were SRL ± MMF (62%), SRL + TAC (21.5%), SRL + CSA (16.5%). The cumulative probability of biopsy-confirmed acute rejection (BCAR) was 5% (n = 22), death-censored graft loss 12% (n = 56) and death 6% (n = 22), and there was no significant relationship to the treatment combination employed. Median calculated creatinine clearance was 48.4 (29.3, 64.5) mL/min at conversion, rising to 54.1 (41.2, 69.0) mL/min at month 1, 55.7 (39.0, 73.0) mL/min at month 12, 58.6 (39.7, 75.2) mL/min at two years and 60.9 (36.0, 77.0) mL/min at three years post-conversion. The most common adverse events were hypertension (47%), hyperlipidemia (26%), urinary tract infections (25%), anaemia (24%) and diarrhea (14%), and cardiac events, hyperlipemia and CMV infection were more common in patients converted during the first year. SRL was most frequently combined with MMF after conversion, but principal clinical outcomes were not significantly influenced by the treatment combination employed in normal practice.

Individualizing Early Use of Sirolimus in Renal Transplantation

One of the main goals in the current care of kidney transplant recipients is to extend long-term graft survival. Efficacious immunosuppressive agents devoid of nephrotoxicity are needed. In human clinical transplantation, sirolimus combined with other immunosuppressive drugs has proven to be a powerful immunosuppressant capable of preventing acute graft rejection, as well as of improving renal function, renal histology, and graft survival when compared with immunosuppressive regimens that include calcineurin inhibitors. The valuable experience gained through many clinical studies allows clinicians to plan sirolimus use. We present a review of the clinical experience and literature review on the use of sirolimus in the first 12 months posttransplantation.