scholarly journals Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Stephania Contreras-Castillo ◽  
Anita Plaza ◽  
Jana Stojanova ◽  
Gustavo Navarro ◽  
Rodolfo Carmona ◽  
...  
Keyword(s):  
Latin American ◽  
Therapeutic Range ◽  
Drug Disposition ◽  
Immunosuppressive Treatment ◽  
Allelic Frequency ◽  
Therapeutic Drug ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Kidney Recipients ◽  
The Impact

Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely CYP3A4, CYP3A5, MDR1 and POR genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations. Using TaqMan® probes, we determined the allelic frequency of seven variants in CYP3A4, CYP3A5, MDR1 and POR in 139 Chilean renal transplant recipients, of which 89 were treated with CsA and 50 with TAC. We tested associations between variants and trough and/or 2-hour concentrations, normalized by dose (C0/D and C2/D) at specific time points post-transplant. We found that CYP3A5*3/*3 carriers required lower doses of TAC. In TAC treated patients, most CYP3A5*3/*3 carriers presented higher C0/D and a high proportion of patients with C0 levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering CYP3A5 genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients.

scholarly journals Mycophenolic Acid Concentration on Vietnamese Renal Transplant Recipients

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Dung Thi Mai Dung ◽  
An Phan Hai Ha ◽  
Dong Van Le ◽  
Lan Thi Phuong Dam ◽  
Thuan Quang Huynh
Keyword(s):  
Renal Transplant ◽  
Mycophenolic Acid ◽  
Calcineurin Inhibitor ◽  
Drug Level ◽  
Therapeutic Drug ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Post Transplantation ◽  
Kidney Recipients ◽  
Number Of Patients

Background: Kidney recipients often use a calcineurin inhibitor and a proliferation inhibitor after transplantation. The therapeutic drug monitoring for calcineurin inhibitor is more simple and feasible in clinical than proliferation inhibitor. In Vietnam, mycophenolic acid is a popular proliferation inhibitor used for transplantation patients. Although therapeutic mycophenolic acid monitoring is so important in treating kidney transplantation, the monitoring is still difficult to execute in Vietnam. Objectives: This study aimed to determine the MPA concentration on Vietnamese renal transplant recipients. Methods: This observational study was conducted on 35 adult kidney recipients to evaluate the MPA concentration at five sampling time points (predose, 1, 2, 3, and 6 hours) on day 3, day 10, and month 6 after transplantation. Results: Plasma MPA trough levels (C0) were 2.32 ± 1.47;1.58 ± 1.39; 2.29 ± 1.4 mg/L and the MPA-AUC0-12 h values were 50.1 ± 20.4; 41.9 ± 14.5; 60.3 ± 25.9 mg.h/L on day 3, day 10, and month 6. The number of patients who reached MPA-AUC0-12 h values of 30 - 60 mg.h/L was 18 (51.4%), 23 (65.7%) and 17 (51.5%) on day 3, day 10, and month 6, respectively. The number of patients who achieved the MPA C0 values of 1.5 - 2.5 mg/L was 15 (42.9 %), 14 (40%), and 10 (30.3%) on day 3, day 10, and month 6, respectively; and the linear correlation coefficients between AUC0-12 h and C0 were 0.652, 0.415, and 0.752, respectively. Conclusions: In renal transplant patients, the MPA-AUC0-12 h was lower on day 3 and day 10 post-transplantation than month 6 for the half dose of MMF or MPS. Therefore, MPA therapeutic drug level should be monitored usually in transplantation patients who use MPA.

scholarly journals Use of Anti-Cytokine Therapy in Kidney Transplant Recipients with COVID-19

2021 ◽  
Vol 10 (8) ◽  
pp. 1551
Author(s):  
Marta Bodro ◽  
Frederic Cofan ◽  
Jose Ríos ◽  
Sabina Herrera ◽  
Laura Linares ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Ordinal Scale ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Recipients ◽  
Secondary Infections ◽  
Statistical Effect ◽  
Randomized Control ◽  
The Impact ◽  
To Receive

In the context of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to evaluate the impact of anti-cytokine therapies (AT) in kidney transplant recipients requiring hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is an observational retrospective study, which included patients from March to May 2020. An inverse probability of treatment weighting from a propensity score to receive AT was used in all statistical analyses, and we applied a bootstrap procedure in order to calculate an estimation of the 2.5th and 97.5th percentiles of odds ratio (OR). outcomes were measured using an ordinal scale determination (OSD). A total of 33 kidney recipients required hospitalization and 54% of them received at least one AT, mainly tocilizumab (42%), followed by anakinra (12%). There was no statistical effect in terms of intensive care unit (ICU) admission, respiratory secondary infections (35% vs. 7%) or mortality (16% vs. 13%) comparing patients that received AT with those who did not. Nevertheless, patients who received AT presented better outcomes during hospitalization in terms of OSD ≥5 ((OR 0.31; 2.5th, 97.5th percentiles (0.10; 0.72)). These analyses indicate, as a plausible hypothesis, that the use of AT in kidney transplant recipients presenting with COVID-19 could be beneficial, even though multicenter randomized control trials using these therapies in transplanted patients are needed.

scholarly journals A Review of Enteric-coated Mycophenolate Sodium for Renal Transplant Immunosuppression

2009 ◽  
Vol 1 ◽  
pp. CMT.S2218 ◽  
Author(s):  
Nathan Newbold ◽  
Brianna Riley ◽  
Karen Hardinger
Keyword(s):  
Renal Transplant ◽  
Mycophenolic Acid ◽  
Renal Transplant Recipients ◽  
Inosine Monophosphate Dehydrogenase ◽  
Transplant Recipients ◽  
Gastrointestinal Complications ◽  
Mycophenolate Sodium ◽  
Delayed Release ◽  
Enteric Coated ◽  
The Impact

Mycophenolic acid inhibits an enzyme, inosine monophosphate dehydrogenase (IMPDH), blocking purine synthesis of lymphocytes and therefore functioning as an effective immunosuppressive agent in transplantation. Currently, there are two available forms of mycophenolic acid (MPA) available; mycophenolate mofetil (MMF) and enteric-coated, delayed-release mycophenolate sodium (EC-MPS). Both products are approved for prophylaxis of organ rejection in renal transplant recipients. The use of MPA may be associated with adverse gastrointestinal effects which can lead to a reduction of the dose or discontinuation of therapy. Enteric-coated MPS was developed to reduce the upper gastrointestinal side effects due to its delayed release in the small intestines. Similar systemic MPA exposure is provided by oral administration of MMF 1000 mg daily and EC-MPS 720 mg, which contain near equimolar MPA content. Clinical trials in renal transplant recipients have demonstrated that EC-MPS is therapeutically equivalent to MMF when used at the time of transplantation and when used for conversion for gastrointestinal complications. The available literature regarding the incidence and severity of gastrointestinal adverse effects and the impact on quality of life remains controversial. Prospective, randomized trials of the available MPA formulations are warranted to further explore the gastrointestinal adverse effect profiles.

scholarly journals 1737. Impact of Therapeutic Drug Monitoring (TDM) of Azole Prophylaxis in Lung Transplant Recipients on the Development of Positive Fungal Events

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S636-S636
Author(s):  
Anooj Shah ◽  
Carly D’Agostino ◽  
Kathleen Cunningham ◽  
Clare Kane ◽  
Michael G Ison ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Study Groups ◽  
Fungal Species ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Lung Transplant Recipients ◽  
Index Value ◽  
The Impact

Abstract Background The utility and clinical impact of therapeutic drug monitoring (TDM) of prophylactic azole antifungals in lung transplant recipients is not well described. The objective of this study was to investigate the impact of TDM of azole prophylaxis in lung transplant recipients on the development of positive fungal events. Methods A retrospective analysis was performed on 47 lung transplant recipients between 2013 and 2018 at Northwestern Memorial Hospital. A positive fungal event was defined as fungal species on BAL culture and/or positive BAL Aspergillus galactomannan (GM) with an index value ≥1.0. Study groups were defined based on attainment of therapeutic trough levels after initiation of oral therapy (therapeutic if posaconazole level ≥0.7 μg/mL or voriconazole ≥1–5.5 μg/mL, subtherapeutic if ≥2 consecutive levels of posaconazole <0.7 μg/mL or voriconazole <1 μg/mL after initial dose increase). Results There were no differences in baseline characteristics (Figure 1). There were a total of 11 fungal events with 3 (12.0%) occurring in the therapeutic cohort and 8 (36.4%) in those subtherapeutic (P = 0.08). In the 5 patients with a positive GM, the mean index was 2.02 ± 0.95. 7/30 (23.3%) of patients on posaconazole had a fungal event, with 2/7 (28.6%) requiring treatment at the time of event. For patients on voriconazole, 4/17 (23.5%) had a fungal event, with 1/4 (25.0%) requiring treatment. Mean time to fungal event was 164.5 ± 8.9 days vs. 135.9 ± 13.7 days in the therapeutic and subtherapeutic group, respectively (P = 0.05). All patients on posaconazole suspension who experienced a fungal event were subtherapeutic (3/3, 100%) compared with the majority of patients on posaconazole delayed release (DR) tablets who achieved therapeutic levels (17/22, 77.3%). Mean posaconazole trough level observed in the patients receiving DR tablet was 2.15 ± 0.95 μg/mL. Conclusion There was an association between two consecutive subtherapeutic azole prophylaxis levels and positive fungal events indicating a role for TDM in lung transplant recipients. Time to fungal event post-transplant was shorter in subtherapeutic patients. As anticipated, the use of posaconazole suspension resulted in subtherapeutic levels. This study presents an opportunity for further research of the impact of TDM on clinical outcomes to optimize patient care. Disclosures All authors: No reported disclosures.

Vaccination titres pre- and post-transplant in paediatric renal transplant recipients and the impact of immunosuppressive therapy

2018 ◽  
Vol 33 (5) ◽  
pp. 897-910 ◽  
Author(s):  
Britta Höcker ◽  
Martin Aguilar ◽  
Paul Schnitzler ◽  
Lars Pape ◽  
Martin Bald ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Immunosuppressive Therapy ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Post Transplant ◽  
The Impact
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