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Everolimus for BKV nephropathy in kidney transplant recipients: a prospective, controlled study.

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Abstract

There is no specific therapy for polyoma BK virus nephropathy (BKVN) in kidney transplant recipients, a condition associated with poor outcomes. Everolimus showed promising antiviral effects, but data from prospective studies are limited. Therefore, we converted ten consecutive kidney transplant recipients with biopsy-proven BKVN from standard exposure Calcineurin inhibitors and Mycophenolate to Everolimus and reduced exposure Calcineurin inhibitors. Ten patients not administered Everolimus, on reduced exposure Calcineurin inhibitor and halved MPA doses served as controls. All kidney transplant recipients continued steroid therapy. Each patient underwent kidney graft biopsy, BKV replication by PCR, and de novo DSA determination. During a 3-year follow-up no graft loss occurred in kidney transplant recipients on Everolimus but it was observed in 5/10 controls (P = 0.032). eGFR improved on Everolimus and worsened in controls (between group difference + 25.6 ml/min/1.73 m2, 95% CI 10.5–40.7, P = 0.002). BKV replication declined in the Everolimus group alone (from 6.4 ± 0.8 to 3.6 ± 1.6 Log 10 genomic copies, P = 0.0001), and we found a significant inverse relationship between eGFR and BKV genomic copy changes (P = 0.022). Average Calcineurin inhibitors trough levels did not differ between the two study groups during follow-up. By multivariable Cox regression analysis, Everolimus treatment resulted the only significant predictor of survival free of a combined endpoint of graft loss and 57% eGFR reduction (P = 0.02). Kidney transplant recipients on Everolimus had a higher survival free of adverse graft outcome (log-rank test, P = 0.009). In conclusion an Everolimus-based immunosuppressive protocol with minimization of Calcineurin inhibitors and antimetabolite discontinuation effectively treated BKVN in kidney transplant recipients.

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Abbreviations

BKV:

Polyoma BK virus

BKVN:

Polyoma BK virus associated nephropathy

KTRs:

Kidney transplant recipients

EVR:

Everolimus

CNI:

Calcineurin inhibitors

MMF:

Mycophenolate mofetil

DSA:

Donor specific antibodies

eGFR:

Estimated glomerular filtration rate

KTRs:

Kidney transplant recipients

TAC:

Tacrolimus

CsA:

Cyclosporine

mTOR:

Mammalian target of rapamycin

BPAR:

Biopsy proven acute rejection

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Authors and Affiliations

  1. Nephrology, Dialysis, and Transplantation, University of Genova, and Policlinico San Martino, Largo R. Benzi 10, 16132, Genoa, Italy

    Elisabetta Bussalino, Luigina Marsano, Angelica Parodi, Rodolfo Russo, Fabio Massarino, Maura Ravera, Giacomo Garibotto & Ernesto Paoletti

  2. Pathology Unit, Policlinico San Martino, Genoa, Italy

    Gabriele Gaggero

  3. Renal Transplant Unit, Policlinico San Martino, Genoa, Italy

    Iris Fontana

  4. Renal Unit, Department of Medicine, University Hospital of Verona, Verona, Italy

    Gianluigi Zaza

  5. Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy

    Giovanni Stallone

Authors
  1. Elisabetta Bussalino
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  2. Luigina Marsano
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  3. Angelica Parodi
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  4. Rodolfo Russo
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  7. Gabriele Gaggero
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  10. Gianluigi Zaza
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  11. Giovanni Stallone
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  12. Ernesto Paoletti
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Contributions

EB participated in the design of the study, in performing research, and in data analysis, and wrote the paper. GZ, GS participated in the design of the study, and in performing research. LM, AP, RR, FM, and IF participated in performing research. MR participated in data analysis. GG and GG participated in performing research, and evaluated biopsies. EP participated in the design of the study, in performing research, in data analysis, and revised the paper.

Corresponding author

Correspondence to Ernesto Paoletti.

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The authors declare that they have no conflict of interest.

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

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Bussalino, E., Marsano, L., Parodi, A. et al. Everolimus for BKV nephropathy in kidney transplant recipients: a prospective, controlled study.. J Nephrol 34, 531–538 (2021). https://doi.org/10.1007/s40620-020-00777-2

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  • DOI: https://doi.org/10.1007/s40620-020-00777-2

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