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.

scholarly journals Influence of TGFB1 and CTLA4 polymorphisms on calcineurin inhibitors dose and risk of acute rejection in renal transplantation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Bogacz ◽  
Marlena Wolek ◽  
Jerzy Sieńko ◽  
Bogusław Czerny ◽  
Bogusław Machaliński ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Immunosuppressive Treatment ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Dose Ratio ◽  
Blood Concentrations ◽  
Organ Rejection ◽  
Transplant Patients ◽  
The Impact ◽  
Tgf Β1

AbstractOrgan transplant is often the treatment of choice as it extends and improves patient life. Immunosuppressive treatment, which prevents acute rejection of the organ, is used in transplant patients to prevent the loss of transplant. The aim of the study was to determine the impact of the CTLA4 (+49A>G, rs231775) and the TGF-β1 (−800G>A, rs1800468) polymorphisms on the therapeutic effect of immunosuppressive drugs (cyclosporine—CsA, tacrolimus—TAC) and the risk of acute rejection in renal transplant patients. The analysis of the CTLA4 +49A>G and the TGF-β1 −800G>A polymorphisms was carried out in 392 patients after kidney transplant using real-time PCR. The CTLA4 +49A>G polymorphism did not affect CsA or TAC dose, ratio of drug concentration to dose (C/D), and blood concentrations. As for the TGF-β1 -800G>A polymorphism, patients with the GA genotype required lower TAC doses compared to the GG genotype (TAC 12 h: 3.63 mg vs 5.3 mg, TAC 24 h: 2.38 mg vs 3.29 mg). Comparing the C/D ratio in both groups (TAC 12 h and TAC 24 h), higher C/D ratio was observed in patients with the GA genotype. These results indicate that patients with the A allele require slightly lower doses of TAC. The results suggest that the TGF-β1 −800 G>A polymorphism may influence the TAC dose, while the +49A>G polymorphism of the CTLA4 gene does not correlate with the dose of CsA or TAC. The analysis of the biochemical parameters of the renal profile showed no impact of the CTLA4 and the TGF-β1 polymorphisms on the risk of organ rejection.

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.

scholarly journals Change of the pattern of management of the kidney transplant patients with terminal stage of chronic renal failure

2018 ◽  
Vol 2 (1) ◽  
pp. 53-55
Author(s):  
R. Salutin
Keyword(s):  
Immunosuppressive Therapy ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Wound Complications ◽  
Clinical Use ◽  
Surgical Wound ◽  
Moderate Risk ◽  
Transplant Patients ◽  
Antiviral Effects ◽  
Kidney Transplant Patients

The review presents results of clinical use of mTOR inhibitors, in particular, everolimus, in immunosuppressive therapy regimens. It has been established that immunosuppressive therapy regimens including mTOR inhibitors are preferred in patients with high and moderate risk of graft loss.The analysis of the clinical use of mTOR inhibitors has provided evidence of the comparative incidence rate of wound complications and terms of surgical wound healing in the treatment with everolimus and the routine therapy.Results of clinical trials have evidenced that minimization of therapy with calcineurin inhibitors and switching patients to everolimus allows for improvement of remote results of the kidney transplantation both due to reduced risk of nephrotoxic effect of calcineurin inhibitors, and due to anti-tumour and antiviral effects.

mTOR Inhibitors Maintain Low Levels of Immune Activation, Immune Senescence and EBV Load in Kidney Transplant Patients

2018 ◽  
Vol 102 ◽  
pp. S201
Author(s):  
Lucrezia Furian ◽  
Maria Raffaella Petrara ◽  
Flavia Neri ◽  
Cristina Silvestre ◽  
Eva Muraro ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Immune Activation ◽  
Mtor Inhibitors ◽  
Immune Senescence ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Low Levels

Long-term Results of Conversion From Calcineurin Inhibitors to Sirolimus in 150 Maintenance Kidney Transplant Patients

2012 ◽  
Vol 10 (2) ◽  
pp. 110-118 ◽  
Author(s):  
Cyril Garrouste ◽  
Nassim Kamar ◽  
Céline Guilbeau-Frugier ◽  
Joëlle Guitard ◽  
Laure Esposito ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Calcineurin Inhibitors ◽  
Long Term Results ◽  
Transplant Patients ◽  
Kidney Transplant Patients

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 Beneficial Effect of Conversion to Belatacept in Kidney-Transplant Patients with a Low Glomerular-Filtration Rate

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Julie Belliere ◽  
Céline Guilbeau-Frugier ◽  
Arnaud Del Bello ◽  
Laure Esposito ◽  
Caroline Capuani ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Kidney Transplant ◽  
Kidney Function ◽  
Filtration Rate ◽  
Case Reports ◽  
Rescue Therapy ◽  
Mtor Inhibitors ◽  
Transplant Patients ◽  
Kidney Transplant Patients

Belatacept has been found to be efficient at preserving good kidney function in maintenance kidney-transplant patients. Herein, we report on the use of belatacept as a rescue therapy for two kidney-transplant patients presenting with severe adverse events after treatment with calcineurin inhibitors (CNIs) and mammalian target-of-rapamycin (mTOR) inhibitors. Two kidney-transplant patients developed severely impaired kidney function after receiving CNIs. The use of everolimus was associated with severe angioedema. Belatacept was then successfully used to improve kidney function in both cases, even though estimated glomerular-filtration rate before conversion was <20 mL/min. These case reports show that belatacept can be used as a rescue therapy, even if kidney function is very low in kidney-transplant patients who cannot tolerate CNIs and/or mTOR inhibitors.

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