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Preventive effect of early introduction of everolimus and reduced-exposure tacrolimus on renal interstitial fibrosis in de novo living-donor renal transplant recipients

  • Hiroaki Ishida
  • Go Ogura
  • Saeko Uehara
  • Shinya Takiguchi
  • Yousuke Nakagawa
  • Naoto Hamano
  • Masahiro Koizumi
  • Takehiko Wada
  • Masafumi Fukagawa
  • Michio NakamuraEmail author
Original article
  • 26 Downloads

Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

Our modified immunosuppressive regimen may have an antifibrotic effect on transplanted kidneys without loss of safety and efficacy.

Keywords

Everolimus Mammalian target of rapamycin inhibitor Tacrolimus Interstitial fibrosis Renal transplantation 

Notes

Acknowledgements

We are grateful to Chisa Okada at the Support Center for Medical Research and Education, Tokai University, for analyzing the images.

Author contributions

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.

Funding

None.

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

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Japanese Society of Nephrology 2019

Authors and Affiliations

  • Hiroaki Ishida
    • 1
  • Go Ogura
    • 3
  • Saeko Uehara
    • 1
  • Shinya Takiguchi
    • 1
  • Yousuke Nakagawa
    • 2
  • Naoto Hamano
    • 2
  • Masahiro Koizumi
    • 2
  • Takehiko Wada
    • 2
  • Masafumi Fukagawa
    • 2
  • Michio Nakamura
    • 1
    Email author
  1. 1.Department of Transplant SurgeryTokai University School of MedicineIseharaJapan
  2. 2.Division of Nephrology, Endocrinology and MetabolismTokai University School of MedicineIseharaJapan
  3. 3.Department of PathologyTokai University School of MedicineIseharaJapan

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