Sirolimus Conversion Efficacy for Graft Function Improvement and Histopathology in Renal Recipients with Mild to Moderate Renal Insufficiency

Abstract

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.Graphical Abstract

A Randomized Clinical Trial on Combination Use of Sirolimus and Tacrolimus in Renal Transplant: A De novo Immunosuppression Approach

“…It is notable that the use of SRL without CNIs did not improved post-transplant outcome in terms of acute rejection, graft function and survival in previous studies [20][21][22]. The early use of SRL is associated with a series complication such as impaired wound healing, hyperlipidemia, new onset diabetes after transplantation (NODAT) [23,24]. Many of this complication depend on the initiation time for SRL consumption after transplantation and dose of the medication.…”