Real life experience with mTOR-inhibitors after lung transplantation

Bos, Saskia; Sadeleer, Laurens J. De; Yserbyt, Jonas; Dupont, Lieven; Godinas, Laurent; Verleden, Geert M.; Ceulemans, Laurens J.; Vanaudenaerde, Bart M.; Vos, Robin

doi:10.1016/j.intimp.2021.107501

Cited by 9 publications

(16 citation statements)

References 10 publications

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“…The commonly reported adverse effects of mTOR inhibitors are presented in Table 2 with dyslipidemia, infections, hematological and mucocutaneous disorders, edema, and proteinuria being the most common. 12,32,[41][42][43][47][48][49] The discontinuation rate of EVL varies considerably. High discontinuation rates of 50-71% were reported in 4 studies.…”

Section: Safety and Tolerability Of Mtor Inhibitors In Lung Transplan...mentioning

confidence: 99%

“…In 104 patients with renal insufficiency with a median eGFR of 30 mL/min/1.73 m 2 , Bos et al 12 retrospectively evaluated the differences in the decrease in eGFR after conversion to mTOR inhibitors (predominantly EVL-treated LTR) and reduced CNI dosing according to baseline eGFR. Subanalysis indicated improvement in renal function for eGFR ≤29 mL/min (median eGFR from 24 to 33 mL/min, n = 29, P < 0.0001), but not for eGFR 30–44 mL/min (median eGFR from 36 to 42 mL/min, n = 26, P = 0.1032).…”

Section: The Effect Of Mtor Inhibitors On Kidney Functionmentioning

confidence: 99%

“…8 Although the use of mTOR inhibitors in kidney and heart transplantation recipients has been well studied, [9][10][11] there is a growing body of evidence supporting the role of mTOR inhibitors in reducing nephrotoxic CNI exposure in lung transplant recipients (LTR) with chronic lung allograft dysfunction, cytomegalovirus, and Epstein-Barr virus infection or reactivation, malignancy, and CKD. [12][13][14] However, the above-mentioned kidney-related adverse effects of CNI are also described in patients receiving mTOR inhibitors. These include proteinuria, focal segmental glomerulosclerosis, thrombotic microangiopathy, and acute tubular necrosis.…”

Section: Introductionmentioning

confidence: 99%

“…8 Although the use of mTOR inhibitors in kidney and heart transplantation recipients has been well studied, 9-11 there is a growing body of evidence supporting the role of mTOR inhibitors in reducing nephrotoxic CNI exposure in lung transplant recipients (LTR) with chronic lung allograft dysfunction, cytomegalovirus, and Epstein-Barr virus infection or reactivation, malignancy, and CKD. 12-14…”

Section: Introductionmentioning

confidence: 99%

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Mammalian Target of Rapamycin Inhibitors and Kidney Function After Thoracic Transplantation: A Systematic Review and Recommendations for Management of Lung Transplant Recipients

et al. 2022

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Background. Chronic kidney disease (CKD) after lung transplantation is common and limits the survival of transplant recipients. The calcineurin inhibitors (CNI), cyclosporine A, and tacrolimus being the cornerstone of immunosuppression are key mediators of nephrotoxicity. The mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, are increasingly used in combination with reduced CNI dosage after lung transplantation. Methods. This systematic review examined the efficacy and safety of mTOR inhibitors after lung transplantation and explored their effect on kidney function. Results. mTOR inhibitors are often introduced to preserve kidney function. Several clinical trials have demonstrated improved kidney function and efficacy of mTOR inhibitors. The potential for kidney function improvement and preservation increases with early initiation of mTOR inhibitors and low target levels for both mTOR inhibitors and CNI. No defined stage of CKD for mTOR inhibitor initiation exists, nor does severe CKD preclude the improvement of kidney function under mTOR inhibitors. Baseline proteinuria may negatively predict the preservation and improvement of kidney function. Discontinuation rates of mTOR inhibitors due to adverse effects increase with higher target levels. Conclusions. More evidence is needed to define the optimal immunosuppressive regimen incorporating mTOR inhibitors after lung transplantation. Not only the indication criteria for the introduction of mTOR inhibitors are needed, but also the best timing, target levels, and possibly discontinuation criteria must be defined more clearly. Current evidence supports the notion of nephroprotective potential under certain conditions.

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Section: Safety and Tolerability Of Mtor Inhibitors In Lung Transplan...mentioning

confidence: 99%

Section: The Effect Of Mtor Inhibitors On Kidney Functionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mammalian Target of Rapamycin Inhibitors and Kidney Function After Thoracic Transplantation: A Systematic Review and Recommendations for Management of Lung Transplant Recipients

et al. 2022

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“…Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, are increasingly used after lung transplantation [ 78 ]. To date, there are no specific data nor recommendations regarding their administration during COVID-19 infection.…”

Section: Sars-cov-2-infected Recipient—management Of Immunosuppressionmentioning

confidence: 99%

How COVID-19 Affects Lung Transplantation: A Comprehensive Review

Vachtenheim

Novysedlák

Svorcova

et al. 2022

JCM

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Lung transplant (LuTx) recipients are at a higher risk of developing serious illnesses from COVID-19, and thus, we have closely reviewed the consequences of the COVID-19 pandemic on lung transplantation. In most transplant centers, the overall LuTx activity significantly declined and led to a specific period of restricting lung transplantation to urgent cases. Moreover, several transplant centers reported difficulties due to the shortage of ICU capacities. The fear of donor-derived transmission generated extensive screening programs. Nevertheless, reasonable concerns about the unnecessary losses of viable organs were also raised. The overall donor shortage resulted in increased waiting-list mortality, and COVID-19-associated ARDS became an indication of lung transplantation. The impact of specific immunosuppressive agents on the severity of COVID-19 varied. Corticosteroid discontinuation was not found to be beneficial for LuTx patients. Tacrolimus concentrations were reported to increase during the SARS-CoV-2 infection, and in combination with remdesivir, tacrolimus may clinically impact renal functions. Monoclonal antibodies were shown to reduce the risk of hospitalization in SOT recipients. However, understanding the pharmacological interactions between the anti-COVID-19 drugs and the immunosuppressive drugs requires further research.

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