Incidence of Delayed Graft Function and Wound Healing Complications After Deceased-Donor Kidney Transplantation Is not Affected by De Novo Everolimus

Albano, Laetitia; Berthoux, F; Moal, Marie-Christine; Rostaing, Lionel; Legendre, Christophe; Genin, R; Toupance, Olivier; Moulin, Anne‐Marie; Merville, Pierre; Rérolle, Jean-Philippe; Bayle, François; Westeel, P. F.; Glotz, Denis; Kossari, Niloufar; Lefrançois, N; Charpentier, B; Blanc, Anne-Sandrine; Giambattista, F. Di; Dantal, Jacques

doi:10.1097/tp.0b013e3181aa7d87

Cited by 75 publications

(61 citation statements)

References 41 publications

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“…Kidney transplant patients receiving immunosuppressive therapy with mTOR inhibitors can benefit from less nephrotoxicity by reducing their exposure to CNIs 3, 4, 5, 6, 7, 8. There is a paucity of published data on the use of EVR in combination with Tac in de novo renal transplant recipients.…”

Section: Discussionmentioning

confidence: 99%

Association of Clinical Events With Everolimus Exposure in Kidney Transplant Patients Receiving Low Doses of Tacrolimus

Shihab

Qazi

Mulgaonkar

et al. 2017

American Journal of Transplantation

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A key objective in the use of immunosuppression after kidney transplantation is to attain the optimal balance between efficacy and safety. In a phase 3b, multicenter, randomized, open‐label, noninferiority study, the incidences of clinical events, renal dysfunction, and adverse events (AEs) were analyzed at 12 months in 309 de novo renal transplant recipients receiving everolimus (EVR), low‐dose tacrolimus (LTac), and prednisone. Cox proportional hazard regression modeling was used to estimate the probability of clinical events at specified combinations of time‐normalized EVR and Tac trough concentrations. At 12 months, the highest incidence of treated biopsy‐proven acute rejection (tBPAR) and graft loss occurred most often in patients with EVR trough concentration <3 ng/mL (64.7% and 10.5%, respectively). At 1 month and 12 months, increasing EVR levels were associated with fewer tBPAR events (both p < 0.0001). Low estimated glomerular filtration rate (eGFR) and decreased eGFR occurred more often in patients with lower EVR and higher Tac levels. AEs were most often observed in patients with EVR levels <3 ng/mL. This study supports maintaining an EVR trough concentration of 3–8 ng/mL, when combined with LTac, to achieve balanced efficacy and safety in renal transplant recipients. Trial registration: NCT01025817.

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Section: Discussionmentioning

confidence: 99%

Association of Clinical Events With Everolimus Exposure in Kidney Transplant Patients Receiving Low Doses of Tacrolimus

Shihab

Qazi

Mulgaonkar

et al. 2017

American Journal of Transplantation

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“…Pericardial effusion is a frequent occurrence after heart transplantation, with moderately to large effusions reported in approximately a fifth of recipients (73,(75)(76)(77). Mortality and hospital stay are unaffected (75)(76)(77), although one study suggested an association between pericardial effusions and acute rejection (78).…”

Section: Pericardial and Pleural Effusionsmentioning

confidence: 99%

Everolimus immunosuppression in de novo heart transplant recipients: What does the evidence tell us now?

Zuckermann

Wang

Epailly

et al. 2013

Transplantation Reviews

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“…46 This effect seems not to be associated with everolimus, and has not been seen in patients at risk of developing delayed graft function. 33,47 Wound healing problems and lymphocele formation have also been related to the use of proliferation signal inhibitors. These effects could be related to the antiproliferative effect of these drugs on fibroblasts.…”

Section: Long-term Safetymentioning

confidence: 99%

Long-term outcome of everolimus treatment in transplant patients

Salvadori

Bertoni²

2011

TRRM

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Abstract:The authors review the use of everolimus in long-term studies both in renal and heart transplantation. The pharmacokinetic and pharmacodynamic differences between everolimus and its parent drug, sirolimus are discussed. The improved pharmacokinetic, in particular the improved bioavailability, the reduced half-time and the reduced binding to plasma protein makes everolimus the first choice among the proliferation signal inhibitors. Everolimus is given in almost all studies in association with cyclosporine, but fixed doses of this drug can cause nephrotoxicity. The first studies used everolimus and CsA in fixed doses, but later studies with reduced CsA doses revealed which revealed improved outcomes. Finally, therapeutic drug monitoring became the better choice for both drugs. Recently very high everolimus exposure allowed the use of very low CsA exposure with improvement of the worse side effects linked to the CsA standard dose. The Zeus study revealed a complete and safe CsA withdrawal, thanks to everolimus and mycophenolic acid. In heart transplantation, everolimus resulted in improved outcomes with respect to antiproliferative drugs such as mycophenolic acid and azathioprine. Along with antirejection properties, everolimus provided evidence for antiproliferative effects on several cells. This resulted in fewer viral infections (mainly CMV), anti-atherosclerotic properties (mainly important in heart transplantation, and antineoplastic effect. The latter activity resulted in lower cancer incidence in transplant patients treated by everolimus. An important piece of evidence for this activity is documented by the use of everolimus in the treatment of some cancers, including renal cancer, neuroendocrine cancers and hepatocellular cancers, also outside the field of transplantation.

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Incidence of Delayed Graft Function and Wound Healing Complications After Deceased-Donor Kidney Transplantation Is not Affected by De Novo Everolimus

Abstract: Findings from this randomized, multicenter trial indicate that kidney function recovery, wound healing, efficacy, and tolerance are similar at 3 months posttransplant with immediate or DE in patients at protocol-specified risk of DGF.

Cited by 75 publications

References 41 publications

Association of Clinical Events With Everolimus Exposure in Kidney Transplant Patients Receiving Low Doses of Tacrolimus

Association of Clinical Events With Everolimus Exposure in Kidney Transplant Patients Receiving Low Doses of Tacrolimus

Everolimus immunosuppression in de novo heart transplant recipients: What does the evidence tell us now?

Long-term outcome of everolimus treatment in transplant patients

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