Presentation Authors: Takeshi Ishimura*, Takahito Endo, Shun Nishioka, Naoki Yokoyama, Teruyuki Oda, Satoshi Ogawa, Masato Fujisawa, Kobe, Japan
Introduction: Although some major clinical trials have shown that the introduction of everolimus (EVR) with calcineurin inhibitor (CNI) minimization in patients of kidney transplantation (KTx) at late post-transplant stage have favorable effect on graft function, the influence of these modification in immunosuppressant on histological findings have seldom been discussed. The objective of this study is to investigate the efficacy of EVR addition along with tacrolimus (TAC) dose reduction in immunosuppression in maintenance KTx recipients, as well as its influence on histological findings.
Methods: This study includes 45 patients who were diagnosed as having chronic CNI-induced arteriolopathy (CIA) in protocol biopsy specimens at either 1, 3, 5, or 7 years after KTx. Of these, 25 patients received EVR concomitant with reduced dose of TAC (EVR group), and 20 were maintained on a conventional TAC-based immunosuppression without EVR (Non-EVR group). The targeted EVR trough concentration (C0) was 3-8 ng/ml, and the targeted TAC C0 after adding EVR was set at 2.5 ng/ml. Firstly, we evaluated the histological findings such as arterial hyalinosis score (aah), chronic interstitial fibrosis score (ci) and chronic tubular atrophy score (ct) according to Banff classification. Then, we quantified the extent of fibrotic interstitium in the specimen and defined as fibrosis index(FI;%). Finally, we evaluated the change in estimated glomerular filtration rate (eGFR;ml/min/1.73m2) and each pathological parameter from at the time of diagnosis of CIA to 2 years and to 4 years after the diagnosis.
Results: The changes in eGFR to 2 and 4 years in EVR vs. Non-EVR group were 1.5Â±3.7 vs. -2.0Â±4.9 (p=0.02) and 0.2Â±4.8 vs. -4.2Â±6.2 (p=0.04), respectively. The changes in ci score to 2 and 4 years in EVR vs. Non-EVR group were -0.2Â±0.4 vs. 0.1Â±1.1 and -0.1Â±0.8 vs. 0.7Â±1.0, and those in ct score were -0.2Â±0.4 vs. 0.1Â±1.1 and -0.1Â±0.8 vs. 0.7Â±1.0, respectively. The changes in FI to 2 and 4 years in EVR vs. Non-EVR group were 1.3Â±2.3 vs. 3.5Â±2.0 (p=0.04) and 3.3Â±2.7 vs. 7.26Â±3.6, respectively. The changes in aah score to 2 and 4 years in EVR vs. Non-EVR group were -0.2Â±0.4 vs. 0.1Â±1.1 (p < 0.01) and -0.1Â±0.8 vs. 0.7Â±1.0, respectively.
Conclusions: Late EVR addition concomitant with TAC reduction in maintenance KTx patients have led to preserved eGFR, improved arterial hyalinosis and less progression of fibrosis. These results may be a clue to understand the mechanism of favorable effect of EVR on kidney graft function in maintenance stage.