This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement.
Adult ; Calcineurin Inhibitors/*administration & dosage ; Drug Synergism ; Female ; Graft Rejection/*etiology/*prevention & control ; Graft Survival/drug effects ; Humans ; Immunosuppressive Agents ; Kidney Transplantation/adverse effects/*methods ; Male ; Renal Insufficiency/diagnosis/*therapy ; Republic of Korea ; Severity of Illness Index ; Sirolimus/*administration & dosage ; Transplantation Tolerance/drug effects ; Treatment Outcome

The optimal immunosuppressive strategy for renal transplant recipients at high immunologic risk remains a topic of investigation. This prospective single arm pilot study was undertaken to evaluate the safety and efficacy of a combined tacrolimus and sirolimus regimen in recipients at immunological high risk and to compare outcomes with a contemporaneous control group received tacrolimus and mycophenolate mofetil. Patients that received a renal allograft between 2010 and 2011 at high risk (defined as panel reactive antibodies > 50%, 4 or more human leukocyte antigen mismatches, or retransplantation) were enrolled. All patients received basiliximab induction and corticosteroids. A total of 28 recipients treated with tacrolimus and sirolimus were enrolled in this study and 69 recipients were retrospectively reviewed as a control group. The sirolimus group showed a higher, but not statistically significant, incidence of biopsy proven acute rejection and a lower glomerular filtration rate than the control group. Furthermore, sirolimus group was associated with significant increases in BKV infection (P = 0.031), dyslipidemia (P = 0.004), and lymphocele (P = 0.020). The study was terminated prematurely due to a high incidence of adverse events. A de novo tacrolimus/sirolimus combination regimen may not be an ideal choice for recipients at high immunological risk.
Adult ; Drug Therapy, Combination/methods ; Female ; Graft Rejection/diagnosis/*etiology/*prevention & control ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/administration & dosage/adverse effects ; Kidney Transplantation/*adverse effects ; Longitudinal Studies ; Male ; Middle Aged ; Sirolimus/*administration & dosage/adverse effects ; Survival Rate ; Tacrolimus/*administration & dosage/adverse effects ; Treatment Outcome