mTOR Inhibitors and their Role in Modern Concepts of Immunosuppression

Nashan, Björn

doi:10.1007/s00268-014-2756-z

Cited by 3 publications

(3 citation statements)

References 17 publications

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“…Additionally, smoking, lymphocele and partial closure in a single musculofascial layer are other risk factors [ 8 ]. Immunosuppressives such as mTORi (a class of drugs that inhibit the mechanistic Target Of Rapamycine) are known to carry increased risk of incisional hernia formation [ 5 ]. Our patient’s only associations with these independent risk factors were his age > 50 years and use of mTORi.…”

Section: Discussionmentioning

confidence: 99%

“…The most common complication requiring surgical interventions are anastomotic leak, ureteral obstruction, hematoma, vascular thrombosis and incisional hernia [ 2–4 ]. Commonly, surgical complications initially may mimic medical problems such as drug toxicity or transplant rejection [ 5 ]. Incisional hernias following renal transplantation occur in 8–20% of cases, depending upon surgical technique, particularly based upon the location of incision made.…”

Section: Introductionmentioning

confidence: 99%

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Incarceration of transplanted kidney through incisional hernia

Nawabi

Marlor

Camarata

et al. 2021

Journal of Surgical Case Reports

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Transplanted allograft kidney herniation through an incisional hernia resulting in incarceration is a rare condition with only one other similar case reported in the literature. The primary imaging modalities used to diagnose kidney herniation are graft ultrasound, abdominal computed tomography and abdominal magnetic resonance imaging [Sugi et al. (Imaging of renal transplant complications throughout the life of the allograft: comprehensive multimodality review. Radiographics 2019;39:1327-1355)]. Treatment should be based on patient’s symptoms. This case report highlights the initial presentation of hematuria in a 57-year-old male that eventually led to the diagnosis of a right-sided incarcerated grafted kidney through an incisional hernia. Subsequently, the patient underwent transplant nephrectomy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Incarceration of transplanted kidney through incisional hernia

Nawabi

Marlor

Camarata

et al. 2021

Journal of Surgical Case Reports

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“…Early initiation of mTOR inhibitor-based immunosuppression is more effective in reducing the risk of CMV infection and disease in solid organ transplant recipients [ 17 ]. Furthermore, a probable negative impact of mTOR inhibitors in post-operative surgical complications [ 15 , 18 ] was contradicted by findings from a single-center study in six liver transplant recipients, indicating that the rate of complications after major surgery is similar in patients receiving mTOR inhibitors to those not receiving mTOR inhibitors [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial

Nashan

Schemmer

Braun

et al. 2015

Trials

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BackgroundIntroduction of calcineurin inhibitors had led to improved survival rates in liver transplant recipients. However, long-term use of calcineurin inhibitors is associated with a higher risk of chronic renal failure, neurotoxicity, de novo malignancies, recurrence of hepatitis C viral (HCV) infection and hepatocellular carcinoma. Several studies have shown that everolimus has the potential to provide protection against viral replication, malignancy, and progression of fibrosis, as well as preventing nephrotoxicity by facilitating calcineurin inhibitor reduction without compromising efficacy. The Hephaistos study evaluates the beneficial effects of early initiation of everolimus in de novo liver transplant recipients.Methods/DesignHephaistos is an ongoing 12-month, multi-center, open-label, controlled study aiming to enroll 330 de novo liver transplant recipients from 15 centers across Germany. Patients are randomized in a 1:1 ratio (7–21 days post-transplantation) to receive everolimus (trough levels 3–8 ng/mL) with reduced tacrolimus (trough levels <5 ng/mL), or standard tacrolimus (trough levels 6–10 ng/mL) after entering a run-in period (3–5 days post-transplantation). In the run-in period, patients are treated with induction therapy, mycophenolate mofetil, tacrolimus, and corticosteroids according to local practice. Randomization is stratified by HCV status and model of end-stage liver disease scores at transplantation. The primary objective of the study is to exhibit superior renal function (estimated glomerular filtration rate assessed by the Modification of Diet in Renal Disease (MDRD)-4 formula) with everolimus plus reduced tacrolimus compared to standard tacrolimus at Month 12. Other objectives are: to assess the incidence of treated biopsy-proven acute rejection, graft loss, or death; the incidences of components of the composite efficacy endpoint; renal function via estimated glomerular filtration rate using various formulae (MDRD-4, Nankivell, Cockcroft-Gault, chronic kidney disease epidemiology collaboration and Hoek formulae); the incidence of proteinuria; the incidence of adverse events and serious adverse events; the incidence and severity of cytomegalovirus and HCV infections and HCV-related fibrosis.DiscussionThis study aims to demonstrate superior renal function, comparable efficacy, and safety in de novo liver transplant recipients receiving everolimus with reduced tacrolimus compared with standard tacrolimus. This study also evaluates the antiviral benefit by early initiation of everolimus.Trial registrationNCT01551212.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0626-0) contains supplementary material, which is available to authorized users.

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Safety of mTOR inhibitors in adult solid organ transplantation

Ventura‐Aguiar

Campistol

Diekmann

2016

Expert Opinion on Drug Safety

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In the authors' opinion, mTOR inhibitors are a safe alternative to standard immunosuppression therapy with CNI and mycophenolate/azathioprine. Mild adverse events can be easily managed with an increased awareness and close monitoring of trough levels. Most serious side effects are dose- and organ-dependent. In kidney and heart transplantation mTOR inhibitors may be safely used as either low-dose de novo or through early-conversion. In the liver, conversion 4 weeks post-transplantation may reduce long-term chronic kidney disease secondary to calcineurin nephrotoxicity, without increasing hepatic artery/portal vein thrombosis.

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mTOR Inhibitors and their Role in Modern Concepts of Immunosuppression

Cited by 3 publications

References 17 publications

Incarceration of transplanted kidney through incisional hernia

Incarceration of transplanted kidney through incisional hernia

Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial

Safety of mTOR inhibitors in adult solid organ transplantation

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