Posttransplantation conversion to sirolimus-based immunosuppression: A single center experience

Sirolimus (SRL) has become an option in kidney transplantation, especially among patients who develop chronic allograft nephropathy (CAN). This study sought to evaluate the safety and efficacy of SRL in 103 kidney recipients of mean age 40 years, including 78 recipients of organs from deceased donors. The major reason for conversion was calcineurin inhibitor (CNI) nephrotoxicity (42.3%) followed by CAN (35.4%). A preconversion kidney biopsy was performed in 89 patients with CAN diagnosed in 51. Mean time to conversion was 40.5 months. The new therapy was: SRL/mycophenolate mofetil (MMF)/prednisone (Pred) in 79 patients; SRL/tacrolimus (TAC)/Pred in 15; and other SRL combinations in 9. The target SRL trough level was 5.0 to 8.0 ng/mL. To evaluate the impact of conversion on renal function, we compared the proteinuria and inverse serum creatinine at 3 months before conversion, at conversion, and at 1, 3, 6, 12, and 24 months postconversion. The overall mean follow-up time was 13.2 months. The analysis showed significant improvement in renal function at month 1 postconversion (P <.05) with stabilization thereafter. The SRL/MMF combination frequently induced anemia and/or leukopenia (n = 23). Infections included pneumonia (n = 10), herpes zoster (n = 7), herpes simplex (n = 3), cytomegalovirus (n = 2), histoplasmosis (n = 2), tuberculosis (n = 2), and neurocryptococcosis (n 1). Reasons for SRL discontinuation were myelotoxicity (n = 4), infection (n 3), nephrotoxicity (n = 3), gastrointestinal intolerance (n = 3), myopathy (n = 1), pneumonitis (n = 1), hyperlipidemia (n = 1), and other reasons (n = 3). Graft loss occurred in 29 patients due to CAN (n = 21) followed by death (cardiovascular, n = 2; infectious, n = 2), acute rejection (n = 3), and infection following immunosuppression withdrawal (n = 1). We concluded that SRL represented an option but reducing associated immunosuppression should strongly be considered to minimize the frequent side effects, especially infections.