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Everolimus in kidney transplant recipients at high cardiovascular risk: a narrative review

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Abstract

Kidney transplant recipients (KTRs) are at increased risk of cardiovascular (CV) morbidity and mortality, and side effects induced by immunosuppressive therapy may be a major contributor to this risk, together with traditional CV risk factors. Many strategies have been considered in order to reduce CV risk in KTRs, such as steroid and/or calcineurin inhibitor (CNI) minimization, but current data are inconclusive. The introduction of mammalian target of rapamycin (mTOR) inhibitors, the cornerstone of CNI minimization, in the immunosuppressive protocol may reduce both the incidence and severity of CNI-associated side effects; however, whether this strategy has an impact on CV risk after kidney transplantation needs to be evaluated. To this end, a panel of Italian experts in the field of transplantation was convened in a series of meetings to assess the current literature on the potential of the mTOR inhibitor everolimus as a cardioprotective agent. This narrative review summarizes the panel’s round-table discussions and provides recommendations for CV risk management in KTRs.

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Acknowledgements

We thank Gayle Robins, independent medical writer, who provided editorial assistance and journal styling services prior to submission on behalf of Springer Healthcare Communications. Editorial services were funded by Novartis Farma, Italy.

Collaborators We would like to thank experts in the field of transplantation who participated in the round-table discussions of the ENTROPIA Project: Andrea Ambrosini, Azienda Ospedaliera Fondazione Macchi, Varese, Italy; Lorenzo Arnaboldi, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; Diego Bellino, Division of Nephrology, Dialysis, and Transplantation, University of Genoa, IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genoa, Italy; Luigi Boschiero, Azienda Ospedaliera Borgo Trento, Verona, Italy; Rossana Caldara, IRCCS San Raffaele, Milan, Italy; Manuela Cannone, Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Vicenza, Italy; Mario Carmellini, Department of Medical, Surgical and Neuroscience, Division of Kidney Transplantation, Policlinico Santa Maria alle Scotte, University of Siena, Siena, Italy; Rosa Carrano, Department of Public Health, Section of Nephrology and Renal Transplantation, "Federico II" University, Naples, Italy; Matteo Ciancio Manuelli, UOSD Chirurgia d’Urgenza, Policlinico Tor Vergata, Rome Italy; Marco De Cicco, Azienda Ospedaliera Fondazione Macchi, Varese, Italy; Paride De Rosa, General Surgery and Transplantation Unit, "San Giovanni di Dio e Ruggi D'Aragona" University Hospital, Scuola Medica Salernitana, Salerno, Italy; Stefano Federico, Department of Public Health, Section of Nephrology and Renal Transplantation, "Federico II" University, Naples, Italy; Guido Garosi, Nephrology, Dialysis and Transplantation, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Massimo Iappelli, Nephrology and Transplant Unit, A.O.S. Camillo-Forlanini, Roma, Italy; Giuseppe Iaria, Liver and Kidney Transplant Centre, University of Rome Tor Vergata, Rome, Italy; Stefania Mastrosimone, Nephrology and Dialysis Department, Ca' Foncello Hospital, Treviso, Italy; Enrico Eugenio Minetti, Azienda Ospedaliero Universitaria Careggi, Florence, Italy; Giovanni Piotti, Kidney and Pancreas Transplantation Unit, University Hospital of Parma, Parma, Italy; Gianbenedetto Piredda, UOC Nefrologia, Azienda Ospedaliera Brotzu, Cagliari, Italy; Franco Pisani, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy; Luca Poli, Organ Transplant Unit Paride Stefanini, Sapienza University of Rome, Rome, Italy; Renzo Pretagostini, Department of General Surgery and Organ Transplantation, Sapienza University, Umberto I Hospital, Rome, Italy; Roberto Pulizzi, Nephrology and Dialysis, Policlinico di Modena, Modena, Italy; Teresa Rampino, IRCCS Policlinico San Matteo, Pavia, Italy; Andrea Ranghino, Nephrology, Dialysis and Kidney Transplant Unit, Ospedali Riuniti, Ancona, Italy; Massimo Sabbatini, Department of Public Health, Section of Nephrology and Renal Transplantation, "Federico II" University, Naples, Italy; Angelo Saracino, Centro Regionale Trapianti, Ospedale Madonna delle Grazie Matera, Italy; Paola Todeschini, Department of Nephrology and Dialysis, S. Orsola Hospital, Bologna, Italy; Daniela Vicedomini, General Surgery and Transplantation Unit, "San Giovanni di Dio e Ruggi D'Aragona" University Hospital, Scuola Medica Salernitana, Salerno, Italy; Valentina Vinti, Nephrology and Transplantation, P.O. "Civico, Di Cristina e Benfratelli", Palermo, Italy; Gianluigi Zaza, Department of Medicine, Renal Unit, University and Hospital Trust of Verona, Verona, Italy.

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Authors and Affiliations

  1. Nephrology, Dialysis, and Transplantation, Policlinico San Martino - Università di Genova, Largo Rosanna Benzi, 10, 16132, Genoa, GE, Italy

    Ernesto Paoletti & Elisabetta Bussalino

  2. Renal Transplantation Unit, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy

    Franco Citterio

  3. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy

    Alberto Corsini

  4. IRCCS Multimedica, Milan, Italy

    Alberto Corsini

  5. Cardiovascular Department, University of Bologna, Bologna, Italy

    Luciano Potena

  6. Kidney and Pancreas Transplantation Unit, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy

    Paolo Rigotti

  7. Division of Nephrology, University of Brescia and Spedali Civili General Hospital, Brescia, Italy

    Silvio Sandrini

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

    Giovanni Stallone

Authors
  1. Ernesto Paoletti
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  2. Franco Citterio
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  3. Alberto Corsini
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  4. Luciano Potena
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  5. Paolo Rigotti
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  6. Silvio Sandrini
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  7. Elisabetta Bussalino
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  8. Giovanni Stallone
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Consortia

ENTROPIA Project

  • Andrea Ambrosini
  • , Lorenzo Arnaboldi
  • , Diego Bellino
  • , Luigi Boschiero
  • , Rossana Caldara
  • , Manuela Cannone
  • , Mario Carmellini
  • , Rosa Carrano
  • , Matteo Ciancio Manuelli
  • , Marco De Cicco
  • , Paride De Rosa
  • , Stefano Federico
  • , Guido Garosi
  • , Massimo Iappelli
  • , Giuseppe Iaria
  • , Stefania Mastrosimone
  • , Enrico Eugenio Minetti
  • , Giovanni Piotti
  • , Gianbenedetto Piredda
  • , Franco Pisani
  • , Luca Poli
  • , Renzo Pretagostini
  • , Roberto Pulizzi
  • , Teresa Rampino
  • , Andrea Ranghino
  • , Massimo Sabbatini
  • , Angelo Saracino
  • , Paola Todeschini
  • , Daniela Vicedomini
  • , Valentina Vinti
  •  & Gianluigi Zaza

Contributions

EP, FC, AC, LP, PR, SS and GS were the members of the ENTROPIA expert panel. All the Authors performed the literature search, wrote and revised the paper and approved the final version before submission.

Corresponding author

Correspondence to Ernesto Paoletti.

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Conflict of interest

EP, FC, AC, and GS received honoraria and consultant fees from Novartis Farma; PR, SS, received honoraria and consultant fees from Astellas and Novartis; LP received honoraria and consultant fees from Novartis and Sandoz; EB declares no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Paoletti, E., Citterio, F., Corsini, A. et al. Everolimus in kidney transplant recipients at high cardiovascular risk: a narrative review. J Nephrol 33, 69–82 (2020). https://doi.org/10.1007/s40620-019-00609-y

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