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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

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A Correction to this article was published on 26 December 2019

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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.

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Change history

  • 26 December 2019

    In the Original publication of the article, the co-author name has been misspelled as “Yousuke Nakagawa”.

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Acknowledgements

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

Funding

None.

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Authors and Affiliations

  1. Department of Transplant Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan

    Hiroaki Ishida, Saeko Uehara, Shinya Takiguchi & Michio Nakamura

  2. Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Shimokasuya, Isehara, Japan

    Yousuke Nakagawa, Naoto Hamano, Masahiro Koizumi, Takehiko Wada & Masafumi Fukagawa

  3. Department of Pathology, Tokai University School of Medicine, Shimokasuya, Isehara, Japan

    Go Ogura

Authors
  1. Hiroaki Ishida
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  2. Go Ogura
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  3. Saeko Uehara
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  4. Shinya Takiguchi
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  5. Yousuke Nakagawa
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  6. Naoto Hamano
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  7. Masahiro Koizumi
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  8. Takehiko Wada
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  9. Masafumi Fukagawa
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  10. Michio Nakamura
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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.

Corresponding author

Correspondence to Michio Nakamura.

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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.

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

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Ishida, H., Ogura, G., Uehara, S. et al. Preventive effect of early introduction of everolimus and reduced-exposure tacrolimus on renal interstitial fibrosis in de novo living-donor renal transplant recipients. Clin Exp Nephrol 24, 268–276 (2020). https://doi.org/10.1007/s10157-019-01822-6

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  • DOI: https://doi.org/10.1007/s10157-019-01822-6

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