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172 Everolimus Treatment Reduces the Need for Anti-CMV Prophylaxis in De Novo Heart Transplant Recipients
... Although everolimus was first used in kidney transplantation [28,29], it has demonstrated to be useful in other SOTs (e.g., heart transplantation, where an advantage in the avoidance of allograft vasculopathy has been reported as well as a lesser incidence of CMV-related events [30]). The reduction in CMV infections with everolimus (versus azathioprine or mycophenolate) [30][31][32][33][34][35] is independent of CMV prophylaxis and D/R serostatus [36]. ...
Immunosuppressive therapy reduces the risk for allograft rejection but leaves recipients susceptible to infections. Cytomegalovirus (CMV) is one of the most frequent causes for infection after transplantation and increases the risk for allograft rejection. As lung transplant recipients (LTRs) need to be under immunosuppression for life, they are a vulnerable group. To determine the potential association between the development of CMV infection and the calcineurin inhibitor (CNI) blood levels within previous 90 days, a retrospective review of LTRs was performed. Data from recipients who underwent a lung transplantation (LTx) at our center from January 2011 to December 2018 were collected. The studied recipients, after case/control matching, included 128 CMV-infection cases. The median time from the transplant to the first positive CMV viral load was 291.5 days. In our study, more patients were treated with tacrolimus (91.9%) than with cyclosporine (8.1%). Drug blood levels at selected timepoints showed no statistically significant difference between cases and controls. However, we found that CMV infection was more frequent in the donor-seropositive/recipient-seronegative group, interstitial lung disease (ILD) recipients, LTRs who underwent basiliximab induction, cyclosporine treated recipients, and LTRs with lymphopenia (at the time of CMV infection and 90 days before). In this review of LTRs, no association between the CNI blood level and CMV infection was seen, although other immunity-related factors were found to be influencing, i.e., basiliximab induction, cyclosporine treatment, and lymphopenia.
... Also in heart transplant patients, the use of EVE has been associated to a lesser incidence of CMV-related events versus those subjects receiving azathioprine or mycophenolate [70][71][72][73][74]. In LTx patients, although the first observations indicated a lesser incidence of CMV infection [57], further studies have been unable to confirm these results [12]. ...
Introduction:
Thoracic transplantation represents the definitive therapy for end-stage lung and heart diseases. Over the life of the allograft, upregulation of profibroproliferative mechanisms result in the advancement of chronic rejection. These take the form of bronchiolitis obliterans syndrome (BOS) in a lung recipient and cardiac allograft vasculopathy (CAV) in a heart recipient. The proliferation signal inhibitors (PSI), sirolimus and everolimus, represent a therapeutic option to downregulate this fibroproliferative effect. Additionally, these drugs may result in renal sparing and express potent anti-viral activity. However, they are fraught with substantial and complex toxicities that limit their use.
Areas covered:
In this review, the authors first describe the mechanism of immunosuppression and pharmacokinetics of the PSIs. Subsequently, their use in thoracic transplant recipients for the purposes of renal sparing, anti-cytomegalovirus effect, and antifibroproliferative effects to prolong the onset or arrest progression of BOS and CAV are reviewed. The toxicities associated with PSI use are described, and three areas are focused on in detail: nephrotoxicities, wound healing impairment, and pulmonary toxicities. Finally, the authors summarize the patients in whom PSI use may be advantageous while minimizing potential toxicities.
Expert opinion:
The potential benefits of PSI use in thoracic transplantation make their use attractive. Relative to alternative antiproliferatives, such as mycophenolate or azathioprine, PSI-treated patients experience significantly more serious adverse effects and discontinue treatment significantly more often. It is critical that patients be wisely selected for PSI use in an effort to minimize toxicities.
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