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.

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.

MO1000MAINTENANCE IMMUNOSUPPRESSIVE THERAPY IN PREVENTION OF ACUTE REJECTION AFTER KIDNEY TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Safa Fattoum ◽  
Mohamed Mongi Bacha ◽  
Tasnim Mosbehi ◽  
Nesrine Braiek ◽  
Ezzedine Abderrzhim ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Low Dose ◽  
Immunosuppressive Treatment ◽  
Calcineurin Inhibitors ◽  
Transplant Patients ◽  
Group A ◽  
Kidney Transplant Patients ◽  
Group B

Abstract Background and Aims Acute rejection (AR) is a redoubtable immunological complication after kidney transplantation (KT). Maintenance immunosuppressive treatment (IS) is a corner stone in prevention of AR. The aim of this study was to define the role of different maintenance IS in preventing AR. Method It was a longitudinal, retrospective, analytical study including kidney transplant patients followed up in our department between 1986 and 2019. Our population was divided in 2 groups: group A (129 KT complicated by at least one episode of AR) and group B (491 KT not complicated by AR). Results All patients received low dose of corticosteroids (CS) in their IS. Calcineurin inhibitors (CI) were not prescribed in first intention in 33,3% of groups A patients versus 13,2% in group B. Cyclosporin A (CsA) was prescribed in first intention in 57,4% of group A patients versus 45,7% in group B. Tacrolimus was prescribed in first intention in 9,3% of group A patients versus 41,1% in group B (p<0,0001). All patients received Atimetabolite (AM) in their IS. In first intention, Azathioprin was prescribed in 73,6 % of group A patients and Mycophenolate Mofetil (MMF) was prescribed in 78,6% of group B patients (<0,0001). In first intention, maintenance IS consisted in low dose corticosteroids (CS) associated with AM in 13,5% of our patients. CI was associated to CS and AM in 86,5% of patients. Tritherapy was significantly more used than biotherapy in group A (p<0,0001). Different associations used were CS+Aza, CS+MMF, CS+AZA+CsA, CS+MMF+CsA or CS+MMF+ Tac. From group A, 74,8% of patients received CS+AZA or Cs+AZA+CsA. And from group B, 75,8% of patients received CS+MMF+CsA or CS+MMF+Tac. Conclusion Maintenance IS therapy must be well chosen according to immunological risk in order to prevent AR.

scholarly journals The Effects of Long-Term Immunosuppressive Therapies on the Structure of the Rat Prostate

2020 ◽  
Vol 17 (12) ◽  
pp. 4614
Author(s):  
Marta Grabowska ◽  
Maria Laszczyńska ◽  
Karolina Kędzierska-Kapuza ◽  
Andrzej Kram ◽  
Kamil Gill ◽  
...  
Keyword(s):  
Intermediate Filaments ◽  
Plasma Cells ◽  
Immunosuppressive Treatment ◽  
Immunosuppressive Drugs ◽  
Ventral Prostate ◽  
Immunohistochemical Expression ◽  
Electron Microscopic ◽  
Morphological Alterations ◽  
Rat Ventral Prostate ◽  
The Impact

Background: Little is known about the overall impact of immunosuppressive drugs on the prostate. The study aimed to determine the impact of different protocols of immunosuppressive treatment on the structure of the rat ventral prostate. Methods: For 6 months, 48 male Wistar rats received immunosuppressive drugs: cyclosporin A, tacrolimus, mycophenolate mofetil, rapamycin, and prednisone, according to three-drug protocols. Light and transmission electron microscopic studies, and quantitative evaluation of immunohistochemical expression of selected intermediate filaments, CD117+ mast cells, and CD138+ plasma cells were performed in the rat ventral prostate. Results: In all experimental groups, acini focal hyperplasia, changes to the ultrastructure of the glandular epithelium, changes in the expression of cytokeratins and desmin, and numerous mast and plasma cells in the prostate stroma were found. In cyclosporine-A-based groups, atrophy and numerous intracellular vacuoles were observed. In groups where a three-drug treatment was replaced with rapamycin, morphological alterations were less severe compared to those without conversion. Conclusions: In the rat ventral prostate, (1) immunosuppressive protocols affect the morphology and immunohistochemical expression of intermediate filaments, (2) morphological alterations, expression, and localization of selected proteins are not connected with adenocarcinoma development, and (3) conversion of the treatment to rapamycin may prevent hyperplastic abnormalities.

scholarly journals The impact of calcineurin inhibitors and mammalian target of rapamycininhibitors on anxiety and depression scores in kidney transplant patients

2016 ◽  
Vol 46 ◽  
pp. 1341-1347 ◽  
Author(s):  
Ebru GÖK OĞUZ ◽  
Gülay ULUSAL OKYAY ◽  
Hadim AKOĞLU ◽  
Güner KARAVELİ GÜRSOY ◽  
Zafer ERCAN ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Calcineurin Inhibitors ◽  
Anxiety And Depression ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
The Impact

scholarly journals Use of Belatacept as Alternative Immunosuppression in Three Renal Transplant Patients withDe NovoDrug-Induced Thrombotic Microangiopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Federico Cicora ◽  
Marta Paz ◽  
Fernando Mos ◽  
Javier Roberti
Keyword(s):  
Renal Transplant ◽  
Thrombotic Microangiopathy ◽  
De Novo ◽  
Parvovirus B19 ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Drug Induced ◽  
Transplant Patients ◽  
Proliferation Signal Inhibitors ◽  
Renal Transplant Patients

Thrombotic microangiopathy (TMA), a severe complication of renal transplantation, is a pathological process involving microvascular occlusion, thrombocytopenia, and microangiopathic hemolytic anemia. It generally appears within the first weeks after transplantation, when immunosuppressive drugs are used at high doses.De novoTMA may also be drug-induced when calcineurin inhibitors or proliferation signal inhibitors are used. We report three cases ofde novodrug-induced TMA in renal transplant patients who were managed by replacing calcineurin inhibitors or proliferation signal inhibitors with belatacept, a primary maintenance immunosuppressive drug, which blocks the CD28 costimulation pathway, preventing the activation of T lymphocytes. To identify the cause of TMA, we ruled out HUS, hepatitis C serology, HIV serology, parvovirus B19, cytomegalovirus, anti-HLA antibodies, and prolonged activated partial thromboplastin time. We suspect that the TMA was caused by the calcineurin inhibitors or proliferation signal inhibitors. Belatacept treatment was initiated at a dose of 10 mg/kg on days 1, 5, 14, 28, 60, and 90; maintenance treatment was 5 mg/kg once a month for 1 year. Belatacept, in combination with other agents, prevented graft rejection in three patients.

658: The Impact of Aspergillus Colonization on Acute Rejection and Lymphocytic Bronchiolitis in Lung Transplant Patients

2009 ◽  
Vol 28 (2) ◽  
pp. S294
Author(s):  
S.S. Weigt ◽  
C.-H. Tseng ◽  
C. Huang ◽  
D.J. Ross ◽  
R. Saggar ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Lung Transplant ◽  
Transplant Patients ◽  
The Impact

scholarly journals Title: REAL CLINICAL IMPACT OF DRUG-DRUG INTERACTIONS OF IM-MUNOSUPPRESSANTS IN TRANSPLANT PATIENTS

2021 ◽  
Author(s):  
ANA ISABEL GAGO ◽  
PILAR FONT ◽  
MANUEL CÁRDENAS ◽  
Dolores Aumente ◽  
JOSE RAMÓN DEL PRADO ◽  
...  
Keyword(s):  
Adverse Drug Events ◽  
Clinical Importance ◽  
Tertiary Hospital ◽  
Immunosuppressive Drugs ◽  
Clinical Impact ◽  
Blood Concentrations ◽  
Transplant Patients ◽  
Increased Risk ◽  
Anti Fungal ◽  
Therapy Modification

Aim: The main objective of this study was to determine the prevalence of real DDIs between immunosuppressants and other drugs in transplant patients. Methods: We conducted a prospective, observational 1-year study at a tertiary hospital, including all transplanted patients. We evaluated data from monitoring blood concentrations of immunosuppressive drugs and adverse drug events (ADEs) caused by DDIs. The DDIs were classified as C, D, or X according to their Lexi-Interact rating (C = monitor therapy, D = consider therapy modification, X = avoid combination). The clinical importance of real DDIs was expressed in terms of patient outcomes. The data were analyzed using Statistical Package for Social Sciences (SPSS) package v. 25.0 (IBM Corp., Armonk, NY, USA). Results: A total of 309 transplant patients were included. Their mean age was 52.0 ± 14.7 years (18–79) and 69.9% were male. The prevalence of real DDIs was 21.7%. Immunosuppressive drugs administered with anti-fungal azoles and tacrolimus (TAC) with nifedipine have a great clinical impact. Real DDIs caused ADEs in 22 patients. The most common clinical outcome was nephrotoxicity (1.6%; n=5), followed by hypertension (1.3%; n=4). Suggestions for avoiding category D and X DDIs included: changing the immunosuppressant dosage, using paracetamol instead of non-steroidal anti-inflammatory drugs, and interrupting atorvastatin. The number of drugs prescribed and having been prescribed TAC was associated with an increased risk of real DDIs. Conclusion: There are many potential DDIs described in the literature but only a small percentage proved to be real DDIs, based on the patients´ outcomes.

scholarly journals Management of Immunosuppression in Kidney Transplant Recipients Who Develop Malignancy

2019 ◽  
Vol 8 (12) ◽  
pp. 2189 ◽  
Author(s):  
Danwen Yang ◽  
Natanong Thamcharoen ◽  
Francesca Cardarelli
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Function ◽  
Calcineurin Inhibitors ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Mortality And Morbidity ◽  
Transplant Patients ◽  
Risk Of Cancer ◽  
The Impact

The risk of cancer increases after transplantation. However, the consensus on immunosuppression (IS) adjustment after diagnosis of malignancy is lacking. Our study aims to assess the impact of IS adjustment on mortality of post-kidney transplant patients and allograft outcomes. We retrospectively reviewed the data in our center of 110 subjects. Our results showed IS dose adjustment was not statistically associated with mortality risk (HR 1.94, 95%CI 0.85–4.41, p = 0.12), and chemotherapy was the only factor that was significantly related to mortality (HR 2.3, 95%CI 1.21–4.35, p = 0.01). IS reduction was not statistically associated with worsening graft function (OR 3.8, 95%CI 0.77–18.71, p = 0.10), nor with graft survival (SHR 4.46, 95%CI 0.58–34.48, p = 0.15) after variables adjustment. Creatinine at cancer diagnosis and history of rejection were both negatively associated with graft survival (SHR 1.72, 95%CI 1.28–2.30, p < 0.01 and SHR 3.44, 95%CI 1.25–9.49, p = 0.02). Reduction of both mycophenolate and calcineurin inhibitors was associated with worsening graft function and lower graft survival in subgroup analysis (OR 6.14, 95%CI 1.14–33.15, p = 0.04; HR 17.97, 95%CI 1.81–178.78, p = 0.01). In summary, cancer causes high mortality and morbidity in kidney transplant recipients; the importance of cancer screening should be emphasized.

Sign in / Sign up

Export Citation Format

Share Document