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Effects of late cyclosporine withdrawal on renal graft function and survival

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Abstract

Objective

Attempts to discontinue calcineurin inhibitors (CNIs) early after renal transplantation without conversion to an alternative immunosuppressive have failed due to high rates of acute rejection. Data on “late” CNI withdrawal are lacking so far.

Design and method

We carried out a matched case-control study on the effects of CNI withdrawal on graft loss and mortality in 90 patients (1500 screened) with advanced graft dysfunction (serum creatinine > 3.5 mg/dl) and a cyclosporine-based triple immunosuppressive regimen at the Charité University Hospital, Berlin.

Results

Cyclosporine was withdrawn at a mean of 54.0 ± 32.8 months post-transplant in 45 subjects. Whereas estimated glomerular filtration rate (eGFR) did not significantly differ between the groups at this time (12.4 ± 2.7 vs. 14.7 ± 8.9 in the control group, p = 0.08), it was significantly higher in subjects undergoing withdrawal after 120 months (Δ 4.1 ml/min; p < 0.001). In a Cox regression analysis adjusted for age, gender and eGFR, patients with CNI withdrawal showed better survival rates for the combined endpoint death/graft loss (hazard ratio, HR [95% confidence interval]: 0.19 [0.12–0.33], p = 0.001) compared to matched controls. The survival benefit was significant for the endpoints death (p = 0.01) and graft loss (p = 0.001).

Conclusions

CNI withdrawal was associated with improved survival rates in patients with advanced graft dysfunction in this retrospective analysis.

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Acknowledgements

We thank Simone Voigt for her indefatigable efforts in this study.

Funding

None.

Author information

Authors and Affiliations

  1. Medical Department I, University Hospital Marien Hospital Herne, Ruhr University Bochum, Hölkeskampring 40, 44625, Herne, Germany

    Nikolaos Pagonas, Felix S. Seibert, Frederic Bauer, Konstantinos Markakis, Benjamin Sasko, Nina Babel & Timm H. Westhoff

  2. Department of Cardiology and Angiology, Medical University Brandenburg, Brandenburg, Germany

    Nikolaos Pagonas & Benjamin Sasko

  3. Department of Nephrology, Charité-Campus Benjamin Franklin, Berlin, Germany

    Kourosh Yusefi & Walter Zidek

  4. Department of Medical Statistics, Informatics and Documentation, Jena University Hospital, Jena, Germany

    Theresa Götze & Peter Schlattmann

  5. Department of Surgery, University Hospital Knappschaftskrankenhaus, Ruhr University Bochum, Bochum, Germany

    Richard Viebahn

Authors
  1. Nikolaos Pagonas
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  2. Kourosh Yusefi
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  3. Felix S. Seibert
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  4. Frederic Bauer
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  5. Konstantinos Markakis
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  6. Benjamin Sasko
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  7. Walter Zidek
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  8. Theresa Götze
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  9. Peter Schlattmann
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  10. Richard Viebahn
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  11. Nina Babel
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  12. Timm H. Westhoff
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Contributions

NP: designed and performed study, analyzed data. KY, FSS, FB, KM, BS, WZ, RV, NB: collected data. TG, PS: analyzed data. THW: designed and performed study, wrote the paper.

Corresponding author

Correspondence to Timm H. Westhoff.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Pagonas, N., Yusefi, K., Seibert, F.S. et al. Effects of late cyclosporine withdrawal on renal graft function and survival. J Nephrol 32, 315–321 (2019). https://doi.org/10.1007/s40620-018-0554-7

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  • DOI: https://doi.org/10.1007/s40620-018-0554-7

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