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

Paoletti, Ernesto; Citterio, Franco; Corsini, Alberto; Potena, Luciano; Rigotti, Paolo; Bussalino, Elisabetta; Stallone, Giovanni; Entropia,

doi:10.1007/s40620-019-00609-y

Cited by 9 publications

(6 citation statements)

References 130 publications

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“…There are at least two possible explanations: an antiviral effect of mTOR inhibitors or an immunomodulant action. With respect to the first hypothesis, we underline that a potential positive impact of mTOR inhibitors in the course of several viral infections is already known in the literature ( 22 , 23 ). However, to our best knowledge, our study is the first one to show a positive impact of mTOR inhibitors in the course of SARS-CoV-2 infection on the evolution of the disease.…”

Section: Discussionmentioning

confidence: 94%

mTOR Inhibitor Use Is Associated With a Favorable Outcome of COVID-19 in Patients of Kidney Transplant: Results of a Retrospective Study

et al. 2022

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IntroductionIn solid organ transplant recipients, COVID-19 is associated with a poor prognosis because of immunosuppression. Some studies suggest a potential therapeutic role of mammalian Target of Rapamycin (mTOR) inhibitors in SARS-CoV-2 infection. This study aimed to assess the impact of mTOR employment on the evolution and outcome of SARS-CoV-2 infection in solid organ transplant recipients.MethodsWe enrolled kidney transplant patients attending the Azienda Ospedaliera Universitaria Federico II in Naples and followed up on these patients from March 2020 to June 2021. We evaluated the risk of acquiring the SARS-CoV-2 infection, the clinical presentation of the disease, and its outcome together with the type of immunosuppressive therapy. Finally, we assessed the impact of mTOR inhibitors on relevant clinical metrics of SARS-CoV-2 infection.ResultsWe enrolled 371 patients, of whom 56 (15.1%) contracted SARS-CoV-2 infection during the period of the study. There were no differences observed among the different immunosuppressive therapies concerning the risk of acquiring SARS-CoV-2 infection. In contrast, the type of immunosuppressive therapy had a significant impact on the outcome of the disease. In detail, patients who received mTOR inhibitors, as part of their immunosuppressive therapy, compared to other regimens had a lower chance of developing a moderate or severe form of the disease (OR = 0.8, 95, CI: (0.21–0.92), P = 0.041).ConclusionIn kidney transplant patients, the use of mTOR inhibitors as part of an immunosuppressive regimen is associated with a better prognosis in the case of COVID-19.

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Section: Discussionmentioning

confidence: 94%

mTOR Inhibitor Use Is Associated With a Favorable Outcome of COVID-19 in Patients of Kidney Transplant: Results of a Retrospective Study

et al. 2022

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“…The observed risk of initiating statin therapy, along with existing body of evidence suggesting the role of mTORi in lipid homeostasis leading to hypercholesterolemia and hypertriglyceridemia [ 43 , 47 ], adds a noteworthy dimension to our findings. Despite this side-effect, mTORi appeared to contribute to the stabilization of the atherosclerotic plaque [ 48 , 49 ] and the reduction of left-ventricular hypertrophy [ 50 ]. This could potentially explain why the higher use of statins in our cohort did not translate into an increased risk of cardiovascular events.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of immunosuppressive regimens used as maintenance therapy in kidney transplantation: The CESIT study

Bellini,

Finocchietti,

Rosa

et al. 2024

PLoS ONE

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Maintenance immunosuppressive therapy used in kidney transplantation typically involves calcineurin inhibitors, such as tacrolimus or cyclosporine, in combination with mycophenolate or mechanistic target of rapamycin (mTORi) with or without corticosteroids. An Italian retrospective multicentre observational study was conducted to investigate the risk-benefit profile of different immunosuppressive regimens. We identified all subjects who underwent kidney transplant between 2009 and 2019, using healthcare claims data. Patients on cyclosporine and tacrolimus-based therapies were matched 1:1 based on propensity score, and effectiveness and safety outcomes were compared using Cox models (HR; 95%CI). Analyses were also conducted comparing mTORi versus mycophenolate among tacrolimus-treated patients. Patients treated with cyclosporine had a higher risk of rejection or graft loss (HR:1.69; 95%CI:1.16–2.46) and a higher incidence of severe infections (1.25;1.00–1.55), but a lower risk of diabetes (0.66;0.47–0.91) compared to those treated with tacrolimus. Among tacrolimus users, mTORi showed non-inferiority to MMF in terms of mortality (1.01;0.68–1.62), reject/graft loss (0.61;0.36–1.04) and severe infections (0.76;0.56–1.03). In a real-life setting, tacrolimus-based immunosuppressive therapy appeared to be superior to cyclosporine in reducing rejection and severe infections, albeit with an associated increased risk of diabetes. The combination of tacrolimus and mTORi may represent a valid alternative to the combination with mycophenolate, although further studies are needed to confirm this finding.

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“…Everolimus is not only approved for use in advanced RCC but also for the treatment of advanced breast cancer[ 17 ], pancreatic neuroendocrine tumor[ 18 ], subependymal giant cell astrocytoma associated with tuberous sclerosis[ 19 ], and other tumors. It can also prevent immunological rejection after kidney, liver, or heart transplantation[ 20 ]. The adverse reactions of everolimus mainly affect the digestive system, respiratory system, endocrine system, and skin mucosa[ 21 , 22 ], with interstitial lung disease (ILD) being the most common pulmonary associated toxicity[ 23 - 25 ].…”

Section: Discussionmentioning

confidence: 99%

Pneumocystis jirovecii diagnosed by next-generation sequencing of bronchoscopic alveolar lavage fluid: A case report and review of literature

Cheng¹,

Shen²,

Dong³

et al. 2023

World J Clin Cases

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BACKGROUND The advent of molecular targeted agents and immune checkpoint inhibitors has greatly improved the treatment of advanced renal cell carcinoma (RCC), thus significantly improving patient survival. The incidence of rare drug-related adverse events has gained increased attention. CASE SUMMARY We report a patient with advanced RCC treated with multiple lines of molecular targeted agents and immune checkpoint inhibitors, who developed a pulmonary infection after treatment with everolimus in combination with lenvatinib. Determining the pathogenic organism was difficult, but it was eventually identified as Pneumocystis jirovecii by next-generation sequencing (NGS) of bronchoscopic alveolar lavage fluid (BALF) and successfully treated with trimethoprim-sulfamethoxazole. CONCLUSION Rare pulmonary infections caused by molecular targeted agents are not uncommon in clinical practice, but their diagnosis is difficult. Evaluating BALF with NGS is a good method for rapid diagnosis of such infections.

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

Cited by 9 publications

References 130 publications

mTOR Inhibitor Use Is Associated With a Favorable Outcome of COVID-19 in Patients of Kidney Transplant: Results of a Retrospective Study

mTOR Inhibitor Use Is Associated With a Favorable Outcome of COVID-19 in Patients of Kidney Transplant: Results of a Retrospective Study

Effectiveness and safety of immunosuppressive regimens used as maintenance therapy in kidney transplantation: The CESIT study

Pneumocystis jirovecii diagnosed by next-generation sequencing of bronchoscopic alveolar lavage fluid: A case report and review of literature

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