Does Everolimus Associated With a Low Dose of Cyclosporine in Long-Term Cardiac Transplant Recipients Improve Renal Function? Initial Experience

Boffini, Massimo; Sansone, Fabrizio; Patanè, Francesco; Bonato, Riccardo; Ribezzo, M.; Iacovino, Cristina; Comoglio, Chiara; Rinaldi, Mauro

doi:10.1016/j.transproceed.2009.03.033

Cited by 11 publications

(4 citation statements)

References 6 publications

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“…mTOR inhibitors act by leading to inhibition of translational processes depending on mTORC1 activity, preventing cell-cycle progression from G1 to Sphase in T-cells; moreover, a potential antiviral effect through interruption of certain mTORC pathways or immune deviation has been evidenced. (Boffini et al 2009) . The antiproliferative effect of EVR may represent a therapeutic option in immunosuppressive protocols of LT by reducing both the risk of acute rejection and the process of progressive fibrosis that determines chronic graft rejection.…”

Section: Introductionmentioning

confidence: 99%

Everolimus-based immunosuppressive regimens in lung transplant recipients: Impact on CMV infection

et al. 2015

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Everolimus-based immunosuppressive regimens in lung transplant recipients: impact on CMV infection. / Rittà M.; Costa C.; Solidoro P.; Sidoti F.; Libertucci D.; Boffini M.; Rinaldi M.; Baldi S.; Cavallo R.. -In: ANTIVIRAL RESEARCH. -ISSN 0166-3542. -113(2015), pp. 19-26. Original Citation:Everolimus-based immunosuppressive regimens in lung transplant recipients: impact on CMV infection. Published version:DOI:10.1016/j.antiviral.2014.10.016 Terms of use:Open Access (Article begins on next page) Anyone can freely access the full text of works made available as "Open Access". Works made available under a Creative Commons license can be used according to the terms and conditions of said license. Use of all other works requires consent of the right holder (author or publisher) if not exempted from copyright protection by the applicable law. You may download, copy and otherwise use the AAM for non-commercial purposes provided that your license is limited by the following restrictions: Availability: This is the author's manuscript(1) You may use this AAM for non-commercial purposes only under the terms of the CC-BY-NC-ND license.(2) The integrity of the work and identification of the author, copyright owner, and publisher must be preserved in any copy. ABSTRACTCytomegalovirus (CMV) is one of the most important viral pathogen in solid organ transplant (SOT) recipients, with heart and lung transplant patients being at considerably high risk for CMV direct and indirect effects. Prevention strategies have resulted in significant reduction in disease and CMV related morbidity and mortality. Few studies reported a lower incidence of CMV infections in solid organ transplant recipients treated with immunosuppressive protocols including the mTOR inhibitor everolimus (EVR).Purpose. The aim of the current study was to evaluate the impact of EVR-based immunosuppressive regimens on the occurrence and kinetics of CMV infection in a population of lung transplant recipients, at both systemic and pulmonary level. Thirty-two lung transplants (LT) were investigated; eighteen were on EVR-based immunosuppressive regimens. CMV events occurring in the first two years post-transplantation at both systemic and pulmonary levels were reported.Principal results. No differences were reported in CMV viraemiae occurrence at both oneand two-year follow up between patients undergoing EVR-based and EVR-free immunosuppressive regimens. Considering CMV episodes at pulmonary levels, as determined by routinely performed broncho-alveolar lavages (BAL), during EVRadministration the patients experienced significantly fewer episodes of high-load CMV (as defined by viral loads ≥ 10 5 copies/mL) than during EVR-free immunosuppressive regimens.Major conclusion. EVR-based immunosuppressive regimens in lung transplantation settings appear to be associated to lower incidence of clinically relevant CMV episodes at pulmonary levels, striking the possibility of extending the use of EVR to such a group of transplant recipients.2

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Section: Introductionmentioning

confidence: 99%

Everolimus-based immunosuppressive regimens in lung transplant recipients: Impact on CMV infection

et al. 2015

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“…The principal adverse reaction to CsA therapy in transplant recipients is renal dysfunction, so that kidney damage caused by oral CsA requires medical attention (32,33). Treatment with an increasing doses of CsA resulted in elevated creatinine levels, which were correlated with the CsA level at C2 (r 2 =0.79).…”

Section: Discussionmentioning

confidence: 99%

Optimal sampling time‑point for cyclosporin A concentration monitoring in heart transplant recipients

Jia

et al. 2018

Exp Ther Med

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The present study was performed to determine an optimal time-point for monitoring the concentration of the immunosuppressive drug cyclosporin A (CsA) in heart transplant patients and its efficacy in the prevention of transplant rejection. A total of 32 transplant recipients were randomly assigned for three treatment approaches. Recipients in groups A (n=11), B (n=13) and C (n=8) received oral administration of CsA at doses of 3.2, 3.5 and 4.4 mg/kg, respectively. The plasma CsA concentrations were examined at 2 h intervals over 12 h. Furthermore, their correlation with the 4 h pharmacokinetic profiles as the area under the plasma CsA concentration vs. time curve (AUC 0-4 h) were calculated The efficacy of CsA in inhibiting cardiac allograft rejection was assessed at 2 h after oral CsA intake (C2) and adverse events of the drug were examined in the C2-monitored recipients. The plasma CsA concentration rapidly increased in most recipients with a peak level detected at ~2 h after dosing. Regression analysis revealed that among all time-points assessed, the CsA had the highest correlation with the AUC 0-4 h at C2. At C2, increasing CsA doses exhibited a positive association with the measure of AUC 0-4 h. The efficacy of increasing CsA target levels at C2 in preventing heart transplant rejection was comparable, as the survival rate was 100% in all of the treatment groups. However, the proportion of recipients with side effects in group A was obviously lower than that in the other two groups. In conclusion, C2 is an ideal time-point for monitoring plasma CsA levels with a utility for individualising the next scheduled dose for each patient to ensure that target levels are maintained and achieve a high efficacy and safety of CsA therapy in heart transplant recipients (clinical trial no. 12002610).

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“…Everolimus is an m-TOR inhibitors with a potent anti-proliferation effect. Its high immunosuppressive activity is particularly useful in all cases in which a reduced calcineurin-inhibitors regimen is indicated (105). Its use is also associated with a low incidence of CMV infection in other solid organ transplantation (106).…”

confidence: 99%

CMV management in lung transplant recipients

Solidoro¹,

Costa²,

Libertucci³

et al. 2014

sob

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recipients management relative to the mortality and morbidity and, on the other hand, to the availability of effective antiviral agents as well as new diagnostic techniques and the prophylaxis, diagnosis, and treatment of CMV infections. In lung transplant recipients management is evolving with experience and we are living the sunrise of a new personalized or tailored management era matching, almost in real time, infection, diagnosis, immunity status and therapy. KEY WORDS: CMV infection, lung transplant, acute rejection, chronic rejection, hyperimmune globulins. IntroductionCytomegalovirus (CMV), a member of the beta herpes virus group, causes a spectrum of disorders, which includes serious illness in organ transplant recipients (1-4). Its presence in biological specimens and its role in co-infections and rejection is far to be fully defined. It is the second most common infection among lung transplant recipients, after bacterial pneumonia (5, 6), and is associated with significant morbidity and mortality after transplantation. Although the availability of effective antiviral drugs has decreased CMV-related mortality, the attention in last years has been addressed to its immunobiological role: in fact CMV infections or pneumonia have been associated to chronic rejection (bronchiolitis obliterans syndrome, BOS) in some, but not all, studies (7,8). The endothelium represents the anatomical and functional interface between engrafted donor tissue and the host immune system and interacts dynamically in immunomodulation. This implies an important role for the endothelial cell (EC) in the initiation, maintenance and/or termination of immune interactions affecting the fate of allograft (9). CMV does not directly induce HLA class II on infected human EC, but the rejection associated class II induction within the allograft might be a consequence of IFN-gamma release by activated T CD4+ cells in response to CMV infection (10).

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Does Everolimus Associated With a Low Dose of Cyclosporine in Long-Term Cardiac Transplant Recipients Improve Renal Function? Initial Experience

Cited by 11 publications

References 6 publications

Everolimus-based immunosuppressive regimens in lung transplant recipients: Impact on CMV infection

Everolimus-based immunosuppressive regimens in lung transplant recipients: Impact on CMV infection

Optimal sampling time‑point for cyclosporin A concentration monitoring in heart transplant recipients

CMV management in lung transplant recipients

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