Preventive effect of early introduction of everolimus and reduced-exposure tacrolimus on renal interstitial fibrosis in de novo living-donor renal transplant recipients
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To improve the long-term outcomes following renal transplantation, prevention of renal-allograft interstitial fibrosis (IF), mainly due to calcineurin inhibitors, is an important therapeutic target. Everolimus (EVR) was reported to have antifibrotic effects. We aimed to investigate the safety, efficacy, and IF of our modified immunosuppressive regimen, which includes early introduction of EVR and reduced-exposure tacrolimus (Tac) (EVR group), and compare it with the standard-exposure tacrolimus-based regimen (Tac group) in de novo living-donor renal recipients.
In this retrospective, single-center cohort study, we compared the 2-year clinical courses between the two groups according to intention to treat. Additionally, in patients in whom biopsies were obtained at 1 h, 3 months, and 12 months post-transplant, we compared IF between the groups using imaging analysis.
Overall, 47 patients were included (EVR group, n = 22; Tac group, n = 25). There were no significant differences in renal function and incidences of rejection and viral infections between the groups at the 2-year post-transplant follow-up. However, pathologic imaging analysis (n = 34) revealed chronological progression of IF in the Tac group during the first year post-transplant and no changes in the EVR group (fibrosis rate at 3 months: 20.8 vs. 13.6%, p < 0.001; at 12 months: 24.7 vs. 14.7%, p < 0.001, respectively).
Our modified immunosuppressive regimen may have an antifibrotic effect on transplanted kidneys without loss of safety and efficacy.
KeywordsEverolimus Mammalian target of rapamycin inhibitor Tacrolimus Interstitial fibrosis Renal transplantation
We are grateful to Chisa Okada at the Support Center for Medical Research and Education, Tokai University, for analyzing the images.
HI and MN designed the study. HI analyzed the data. HI, MN, SU, ST, MK, NH, YN, TW, MF, and GO performed the study. HI prepared the manuscript.
Compliance with ethical standards
Conflict of interest
The authors have declared that no conflict of interest exists.
Research involving human participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee at which the studies were conducted (IRB approval number 18R222) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.