Multicenter, Real-World Clinical Evaluation of Alemtuzumab and Anti-Thymocyte Globulin for Severe Acute T Cell-Mediated Kidney Transplant Rejection.

Background: Alemtuzumab can be an alternative to rabbit anti-thymocyte globulin (rATG) to treat severe or glucocorticoid-resistant acute T cell-mediated kidney transplant rejection (TCMR). Yet, there are few reports in which these two treatments are evaluated let alone, compared. This study describes the real-world clinical experience of both therapies and compares their efficacy and toxicity.

New Developments and Therapeutic Drug Monitoring Options in Costimulatory Blockade in Solid Organ Transplantation: A Systematic Critical Review.

Purpose: In this review, the authors summarized the latest developments in costimulatory blockade to prevent rejection after solid organ transplantation (SOT) and discussed possibilities for future research and the need for therapeutic drug monitoring (TDM) of these agents.

Methods: Studies about costimulatory blockers in SOT in humans or animal transplant models in the past decade (2014-2024) were systematically reviewed in PubMed, European Union clinical trials (EudraCT), and ClinicalTrials.gov.

Selecting the Best Pharmacokinetic Models for a Priori Model-Informed Precision Dosing with Model Ensembling.

Background And Objective: When utilizing population pharmacokinetic (popPK) models for a priori dosage individualization, selecting the best model is crucial to obtain adequate doses. We developed and evaluated several model-selection and ensembling methods, using external evaluation on the basis of therapeutic drug monitoring (TDM) samples to identify the best (set of) models per patient for a priori dosage individualization.

Methods: PK data and models describing both hospitalized patients (n = 134) receiving continuous vancomycin (26 models) and patients (n = 92) receiving imatinib in an outpatient setting (12 models) are included.

Model-informed dose optimization of mycophenolic acid in pediatric kidney transplant patients.

Purpose: We aimed to develop and evaluate a population PK model of mycophenolic acid (MPA) in pediatric kidney transplant patients to aid MPA dose optimization.

Methods: Data were collected from pediatric kidney transplant recipients from a Dutch academic hospital (Radboudumc, the Netherlands). Pharmacokinetic model-building and model-validation analyses were performed using NONMEM.

Prediction of the Intra-T Lymphocyte Tacrolimus Concentration after Kidney Transplantation with Population Pharmacokinetic Modeling.

The intracellular tacrolimus concentration in CD3 T lymphocytes is proposed to be a better representative of the active component of tacrolimus than the whole blood concentration. However, intracellular measurements are complicated. Therefore, the aim of this study was to describe the relationship between intracellular and whole blood tacrolimus concentrations in a population pharmacokinetic model.

Challenges for the improvement of valganciclovir prophylaxis in solid organ transplantation and the possible role of therapeutic drug monitoring in adults.

Cytomegalovirus (CMV) infection frequently occurs after solid organ transplantation and is associated with an increased morbidity and mortality. Fortunately, the development of valganciclovir prophylaxis has lowered the incidence of CMV infection and its complications in immunosuppressed solid organ transplant recipients. However, breakthrough infections during valganciclovir prophylaxis and late CMV infection after cessation of valganciclovir prophylaxis still occur with the current prophylactic strategy.

Removing the physician from the equation: Patient-controlled, home-based therapeutic drug self-monitoring of tacrolimus.

The dosing of tacrolimus, which forms the backbone of immunosuppressive therapy after kidney transplantation, is complex. This is due to its variable pharmacokinetics (both between and within individual patients), narrow therapeutic index, and the severe consequences of over- and underexposure, which may cause toxicity and rejection, respectively. Tacrolimus is, therefore, routinely dosed by means of therapeutic drug monitoring (TDM).

Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia.

Background: Chemerin, an inflammatory adipokine, is upregulated in preeclampsia, and its placental overexpression results in preeclampsia-like symptoms in mice. Statins may lower chemerin.

Methods: Chemerin was determined in a prospective cohort study in women suspected of preeclampsia and evaluated as a predictor versus the sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio.

Best practices, implementation and challenges of outpatient parenteral antimicrobial therapy: results of a worldwide survey among healthcare providers.

Background: Outpatient Parenteral Antimicrobial Therapy (OPAT) is considered a patient-friendly and cost-effective practice. Patients in the OPAT service can be at risk for developing adverse events. Due to extensive variations in practice, guidelines have been developed to minimize the risks.

Acetaminophen treatment in children and adults with spinal muscular atrophy: a lower tolerance and higher risk of hepatotoxicity.

Acute liver failure has been reported sporadically in patients with spinal muscular atrophy (SMA) and other neuromuscular disorders with low skeletal muscle mass receiving recommended dosages of acetaminophen. It is suggested that low skeletal muscle mass may add to the risk of toxicity. We aimed to describe the pharmacokinetics and safety of acetaminophen in patients with SMA.

A Decade of Experience With Alemtuzumab Therapy for Severe or Glucocorticoid-Resistant Kidney Transplant Rejection.

Alemtuzumab is used as lymphocyte-depleting therapy for severe or glucocorticoid-resistant kidney transplant rejection. However, the long-term efficacy and toxicity of alemtuzumab therapy are unclear. Therefore, all cases of alemtuzumab anti-rejection therapy between 2012 and 2022 in our institution were investigated.

Therapeutic Drug Monitoring to Optimize Risperidone Treatment in Children with Autism Spectrum Disorder.

Background: Risperidone is an atypical antipsychotic drug used to treat irritability and aggression in children and adolescents with autism spectrum disorder. In an earlier study, the sum trough concentration of risperidone and its metabolite (9-hydroxyrisperidone) was positively correlated with weight gain and effectiveness. The aim of this study was to determine the therapeutic window for risperidone sum trough concentrations that balances weight gain with treatment effectiveness in this population.

A Population Pharmacokinetic Model to Predict the Individual Starting Dose of Tacrolimus for Tunisian Adults after Renal Transplantation.

Background: Tacrolimus is the most frequently used immunosuppressive drug for preventing renal rejection. However, its use is hampered by its narrow therapeutic index and large intra and interpatient variability in pharmacokinetics. The objective of this study was to externally validate a tacrolimus population pharmacokinetic model developed for the Dutch population and adjust the model for the Tunisian population for use in predicting the starting dose requirement after kidney transplantation.

Should we abandon therapeutic drug monitoring of tacrolimus in whole blood and move to intracellular concentration measurements?

The measurement of whole blood (WB) concentrations has been the primary method for therapeutic drug monitoring of tacrolimus since its introduction in the field of organ transplantation. However, >99% of tacrolimus measured in WB is bound to erythrocytes and plasma proteins, which are the pharmacologically inactive fractions. The pharmacologically active fractions, the free (or unbound) tacrolimus in plasma and the intracellular tacrolimus, make up 1% or less of the WB concentration.

Individualized dosing algorithms for tacrolimus in kidney transplant recipients: current status and unmet needs.

Introduction: Tacrolimus is a potent immunosuppressive drug with many side effects including nephrotoxicity and post-transplant diabetes mellitus. To limit its toxicity, therapeutic drug monitoring (TDM) is performed. However, tacrolimus' pharmacokinetics are highly variable within and between individuals, which complicates their clinical management.

Modelling changes in the pharmacokinetics of tacrolimus during pregnancy after kidney transplantation: A retrospective cohort study.

Aims: Pregnancy after kidney transplantation is realistic but immunosuppressants should be continued to prevent rejection. Tacrolimus is safe during pregnancy and is routinely dosed based on whole-blood predose concentrations. However, maintaining these concentrations is complicated as physiological changes during pregnancy affect tacrolimus pharmacokinetics.