Conversion from calcineurin inhibitors to mTOR inhibitors as primary immunosuppressive drugs in pediatric heart transplantation

2017 ◽  
Vol 31 (10) ◽  
pp. e13054 ◽  
Author(s):  
Alfred Asante-Korang ◽  
Jennifer Carapellucci ◽  
Diane Krasnopero ◽  
Abigail Doyle ◽  
Brian Brown ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Immunosuppressive Drugs ◽  
Pediatric Heart Transplantation

scholarly journals Recent Topics on the Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities

2019 ◽  
Author(s):  
Wei Zhang ◽  
Nobuaki Egashira ◽  
Satohiro Masuda
Keyword(s):  
Early Recognition ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Immunosuppressive Drugs ◽  
Individual Therapy ◽  
Therapeutic Drug ◽  
Neuroprotective Effects ◽  
Neuropsychiatric Manifestation ◽  
Neuropsychiatric Complications

Although transplantation procedures have been developed for patients with end-stagec hepatic insufficiency or other diseases, allograft rejection still threatens patient health and lifespan. Over the last few decades, the emergence of immunosuppressive agents, such as calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors, have strikingly increased graft survival. Unfortunately, immunosuppressive agent-related neurotoxicity is commonly occurred in clinical situations, with the majority of neurotoxicity cases caused by CNIs. The possible mechanisms whereby CNIs cause neurotoxicity include: increasing the permeability or injury of the blood-brain barrier, alterations of mitochondrial function, and alterations in electrophysiological state. Other immunosuppressants can also induce neuropsychiatric complications. For example, mTOR inhibitors induce seizures; mycophenolate mofetil induces depression and headache; methotrexate affects the central nervous system; mouse monoclonal immunoglobulin G2 antibody against cluster of differentiation 3 also induces headache; and patients using corticosteroids usually experience cognitive alteration. Therapeutic drug monitoring, individual therapy based on pharmacogenetics, and early recognition of symptoms have greatly reduced neurotoxic events. Once neurotoxicity occurs, a reduction in the drug dosage, switching to other immunosuppressants, using drugs to treat the neuropsychiatric manifestation, or blood purification therapy have proven to be effective against neurotoxicity. In this review, we summarize the recent topics on the mechanisms of neurotoxicity of immunosuppressive drugs. In addition, some information about neuroprotective effects of several immunosuppressants are also discussed.

scholarly journals Role of Kaletra (combination of lopinavir and ritonavir) in the treatment of COVID-19 virus infection; an issue related to kidney transplant patients – A review study on current knowledge

2020 ◽  
Vol 5 (2) ◽  
pp. e28-e28
Author(s):  
Seyed Seifollah Beladi Mousavi ◽  
Fatemeh Hayati ◽  
Ehsan Valavi ◽  
Isa Rezaee ◽  
Shokouh Shayanpour ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
English Language ◽  
Current Knowledge ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Immunosuppressive Drugs ◽  
Current Data ◽  
Blood Concentrations ◽  
Transplant Patients ◽  
Frequent Monitoring

A number of therapies are prescribed for the treatment of COVID-19, but none of them have proven efficacy. In this review article, we summarized the pharmacodynamic and pharmacokinetic properties, effect and potential toxicity of Kaletra (combination of lopinavir and ritonavir) among kidney transplant (KTP) patients who have COVID-19. We used a variety of sources by searching through PubMed, Scopus, Embase and Current Content to collect current data about our issue. Articles published in the English language, as full-text manuscripts, and or as abstract form were included in the study. Lopinavir and ritonavir are two structurally related novel protease inhibitors which have antiretroviral properties. They have primarily been used as part of combination therapy for the treatment of HIV, SARS-CoV and MERS-CoV viruses. However, it seems that use of Kaletra is not associated with clinical improvement, or reduces mortality among patients including KTP recipients who have laboratory-confirmed COVID-19. On the other hand, co-administration of Kaletra with medications that are commonly used among KTP recipients including calcineurin inhibitors and mTOR inhibitors has profound drug-drug interactions. Co-administration of Kaletra with these medications could lead to significant and unexpected increase of blood concentrations of both calcineurin and mTOR inhibitors and therefore frequent monitoring of the immunosuppressive drugs concentrations are necessary to optimize immunosuppressive therapy and prevention of toxicity. It is important to note that frequent monitoring of the immunosuppressive drugs concentration is expensive and also not easily available in many countries including our country. According to the above important points, we recommend that use of Kaletra among KTP patients who have laboratory-confirmed COVID-19 should be avoided especially among patients who are still on calcineurin and mTOR inhibitors.

Biomarkers in blood for individualization of the pharmacotherapy with immunosuppressive drugs after transplantation of solid organs

2015 ◽  
Vol 38 (6) ◽  
Author(s):  
Eberhard Wieland ◽  
Maria Shipkova
Keyword(s):  
Mycophenolic Acid ◽  
Cell Activation ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Immunosuppressive Drugs ◽  
Therapeutic Drug ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Transplantation Medicine ◽  
Pharmacodynamic Biomarkers

AbstractThe success of transplantation medicine is closely associated with the introduction of potent immunosuppressive drugs. Therapy guidance of the calcineurin inhibitors cyclosporine and tacrolimus as well as the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus is achieved by therapeutic drug monitoring (TDM). For other immunosuppressive drugs such as mycophenolic acid, TDM is not established. It has been suggested that a better individualization of pharmacotherapy could be helpful in avoiding over- and under-immunosuppression, which have been associated with poor long-term outcome of grafts and patients. Therefore, a search for biomarkers that could complement TDM, thereby allowing a better individualization of therapy, is ongoing worldwide. Pharmacodynamic biomarkers in transplantation medicine can be either non-drug-specific, aiming at assessing the global effect on the immune system, or drug-specific, aiming at recording the pharmacologic effect on a drug target. Non-specific pharmacodynamic biomarkers can reflect the degree of immune activation by measuring T- or B-cell activation, the development of operational tolerance by monitoring, e.g., regulatory T-cells, or the graft damage by measuring cell-free DNA released by the graft in response to injury. Drug-specific pharmacodynamic biomarkers have been published for mycophenolic acid, calcineurin, and mTOR inhibitors. The field of biomarker research to complement TDM for a better individualization of immunosuppression is still in its infancy, and controlled prospective clinical trials are needed to unravel or dismiss the potential of particular biomarkers or biomarker combinations in various patient cohorts with different grafts.

scholarly journals THE EXPERIENCE OF PEDIATRIC HEART TRANSPLANTATION ON NORTH-WEST OF RUSSIAN FEDERATION

2018 ◽  
Vol 20 (2) ◽  
pp. 37-46 ◽  
Author(s):  
M. A. Simonenko ◽  
T. M. Pervunina ◽  
P. A. Fedotov ◽  
Yu. V. Sazonova ◽  
E. S. Vasichkina ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Clinical Signs ◽  
Calcineurin Inhibitors ◽  
Research Centre ◽  
North West ◽  
Bridge To Transplant ◽  
National Medical ◽  
Long Term Follow Up ◽  
Pediatric Heart Transplantation

Aim:to estimate early and long-term outcomes in recipients under 18 years old who have been heart transplanted in Almazov National Medical Research Centre.Materials and methods. From April 2011 to September 2017 we performed 5 heart transplantations (HTx) in recipients under 18 years old (female) old) from adults donors. The median of age were 15 years (range 10–16 years), LVEF prior HTx – 17% (10–33%). Causes of heart failure were dilated cardiomyopathy (n = 2), non-compacted myocardium (n = 1), arrhythmogenic ventricular dysplasia (n = 1) and Ebstein’s anomaly (n = 1). They spent in HT waiting list 76 days (12–684 days). One patient underwent biventricular assist device Berlin Heart EXCOR implantation (days on support – 250) as a «bridge» to transplant. Due to coronary angiography (CAG) results 1 patient underwent HTx and CABG simultaneously. All recipients treated by triple-drug therapy (steroids, calcineurin inhibitors, mycophenolate mofetil), induction (thymoglobulin – n = 4, basiliximab – n = 1). We evaluated retrospectively laboratory-instrumental investigations and frequency of complications after HTx.Results.The median of survival after HT was 35,93 months (4,4–73,7 months), all of them are alive. Patients spent in ICU 12 days (4–18 days), but one – 18 days due to posterior reversible encephalopathy syndrome (PRES), tacrolimus was switched to cyclosporine. They required inotropic support during 3 days (3–8 days). In 1 yr after HT TTE results got to normal values, the same as VO2peak signifi cantly improved. According to EMB (n = 48) results there were no clinical signs of rejection, acute cellular rejection (R2) was diagnosed in 12,5% cases. In long-term follow-up there was no signifi cant post transplant complications and comorbidities.Conclusion.Pediatric heart transplantation is an effective treatment of terminal CHF. There was no signifi cant clinical rejection under combined immunosuppressive regimens. All patients recovered and went back to normal life. Physical capacity improved in all recipients. 

Neuropsychological Functioning After Pediatric Heart Transplantation

2010 ◽  
Author(s):  
Kelly L. Konopacki ◽  
Jennifer L. Bruno ◽  
Amy M. Wisniewski ◽  
Shelli R. Kesler ◽  
David N. Rosenthal ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Neuropsychological Functioning ◽  
Pediatric Heart Transplantation

Immunosuppressive Management of Pediatric Kidney Transplant Recipients

2020 ◽  
Vol 26 (28) ◽  
pp. 3451-3459
Author(s):  
Tomáš Seeman
Keyword(s):  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Graft Loss ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Therapeutic Drug ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

: Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. : Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. : The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. : Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). : The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.

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