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.

A Mixed Method Study in Young Children Participating in Clinical Research During A Kidney Transplantation Trajectory.

Introduction: Regulations designed to protect children participating in clinical research often restrict the availability of research data necessary for the development of age-specific therapies and drug dosing. Few data exist on how children experience participation in clinical research, and studies investigating young children undergoing an intensive medical treatment are lacking.

Methods: Mixed methods with semi-structured interviews and DISCO-RC questionnaires were used to explore young children's and their parents' experiences in clinical research participation during a kidney transplantation trajectory.

A pre-transplantation risk assessment tool for graft survival in Dutch pediatric kidney recipients.

Background: A prediction model for graft survival including donor and recipient characteristics could help clinical decision-making and optimize outcomes. The aim of this study was to develop a risk assessment tool for graft survival based on essential pre-transplantation parameters.

Methods: The data originated from the national Dutch registry (NOTR; Nederlandse OrgaanTransplantatie Registratie).

Diagnosing, discarding, or de-VUSsing: A practical guide to (un)targeted metabolomics as variant-transcending functional tests.

Purpose: For patients with inherited metabolic disorders (IMDs), any diagnostic delay should be avoided because early initiation of personalized treatment could prevent irreversible health damage. To improve diagnostic interpretation of genetic data, gene function tests can be valuable assets. For IMDs, variant-transcending functional tests are readily available through (un)targeted metabolomics assays.

Perioperative anesthesia care for the pediatric patient undergoing a kidney transplantation: An educational review.

Living-donor kidney transplantation is the first choice therapy for children with end-stage renal disease and shows good long-term outcome. Etiology of renal failure, co-morbidities, and hemodynamic effects, due to donor-recipient size mismatch, differs significantly from those in adult patients. Despite the complexities related to both patient and surgery, there is a lack of evidence-based anesthesia guidelines for pediatric kidney transplantation.

Prognostic Factors on Graft Function in Pediatric Kidney Recipients.

Background: Graft survival in pediatric kidney transplant recipients has increased in the last decades. Determining prognostic factors for graft function over time allows the identification of patients at risk for graft loss and could lead to improvement of current guidelines.

Methods: Data were collected among pediatric kidney transplant recipients in a single center during the first 5 years after transplantation.

Chitotriosidase as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis.

Background: Nephropathic cystinosis, a hereditary lysosomal storage disorder caused by dysfunction of the lysosomal cotransporter cystinosin, leads to cystine accumulation and cellular damage in various organs, particularly in the kidney. Close therapeutic monitoring of cysteamine, the only available disease-modifying treatment, is recommended. White blood cell cystine concentration is the current gold standard for therapeutic monitoring, but the assay is technically demanding and is available only on a limited basis.

Preparing for a kidney transplant: Medical nephrectomy in children with nephrotic syndrome.

Nephrotic syndrome is characterized by proteinuria, hypoalbuminemia, and general edema. These symptoms may persist in children who reach ESRD, which is unfavorable for the patient's allograft outcome. In addition, this may hamper early diagnosis of a relapse after transplantation.

A Population Pharmacokinetic Model Does Not Predict the Optimal Starting Dose of Tacrolimus in Pediatric Renal Transplant Recipients in a Prospective Study: Lessons Learned and Model Improvement.

Background And Objective: Bodyweight-based dosing of tacrolimus is considered standard care. Currently, at first steady state, a third of pediatric kidney transplant recipients has a tacrolimus pre-dose concentration within the target range. We investigated whether adaptation of the starting dose according to a validated dosing algorithm could increase this proportion.

Cellular ciliary phenotyping indicates pathogenicity of novel variants in and confirms a Mainzer-Saldino syndrome diagnosis.

Background: Mainzer-Saldino syndrome (MZSDS) is a skeletal ciliopathy and part of the short-rib thoracic dysplasia (SRTD) group of ciliary disorders. The main characteristics of MZSDS are short limbs, mild narrow thorax, blindness, and renal failure. Thus far, variants in two genes are associated with MZSDS: and .

The potential impact of hematocrit correction on evaluation of tacrolimus target exposure in pediatric kidney transplant patients.

Background: Tacrolimus is an important immunosuppressive agent with high intra- and inter-individual pharmacokinetic variability and a narrow therapeutic index. As tacrolimus extensively accumulates in erythrocytes, hematocrit is a key factor in the interpretation of tacrolimus whole blood concentrations. However, as hematocrit values in pediatric kidney transplant patients are highly variable after kidney transplantation, translating whole blood concentration targets without taking hematocrit into consideration is theoretically incorrect.

Oscillometric and intra-arterial blood pressure in children post-kidney transplantation: Is invasive blood pressure measurement always needed?

Objective: Blood pressure (BP) monitoring in children immediately after kidney transplantation is ideally performed with an arterial line. Accurate measurement of BP is necessary for optimal management. However, during the first days postoperative, the arterial line is removed and BP measurement is switched to a non-invasive device.

A randomized clinical trial indicates that levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome.

Levamisole has been considered the least toxic and least expensive steroid-sparing drug for preventing relapses of steroid-sensitive idiopathic nephrotic syndrome (SSINS). However, evidence for this is limited as previous randomized clinical trials were found to have methodological limitations. Therefore, we conducted an international multicenter, placebo-controlled, double-blind, randomized clinical trial to reassess its usefulness in prevention of relapses in children with SSINS.

A Population Pharmacokinetic Model to Predict the Individual Starting Dose of Tacrolimus Following Pediatric Renal Transplantation.

Background: Multiple clinical, demographic, and genetic factors affect the pharmacokinetics of tacrolimus in children, yet in daily practice, a uniform body-weight based starting dose is used. It can take weeks to reach the target tacrolimus pre-dose concentration.

Objectives: The objectives of this study were to determine the pharmacokinetics of tacrolimus immediately after kidney transplantation and to find relevant parameters for dose individualization using a population pharmacokinetic analysis.

A Novel Hypokalemic-Alkalotic Salt-Losing Tubulopathy in Patients with Mutations.

Mice lacking distal tubular expression of , the gene encoding the tight junction protein Claudin-10, show enhanced paracellular magnesium and calcium permeability and reduced sodium permeability in the thick ascending limb (TAL), leading to a urine concentrating defect. However, the function of renal Claudin-10 in humans remains undetermined. We identified and characterized mutations in two patients with a hypokalemic-alkalotic salt-losing nephropathy.

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe: an ESPN-ERA/EDTA registry analysis.

Background: We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors.

Methods: In this registry analysis, we extracted patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy.

A preliminary study searching for the right dose of tacrolimus in very young (≤4 years) renal transplant patients.

Objectives: The Radboudumc Amalia Children's hospital in the Netherlands has a programme for renal transplantation in children aged ≤4 years. Children receive chronic corticosteroid sparing immunosuppressive therapy that consists of tacrolimus and mycophenolate mofetil. This work aimed to describe the PK of tacrolimus in children ≤4 years with renal transplants.

AGORA, a data- and biobank for birth defects and childhood cancer.

Background: Research regarding the etiology of birth defects and childhood cancer is essential to develop preventive measures, but often requires large study populations. Therefore, we established the AGORA data- and biobank in the Netherlands. In this study, we describe its rationale, design, and ongoing data collection.

Racial Disparities in Access to and Outcomes of Kidney Transplantation in Children, Adolescents, and Young Adults: Results From the ESPN/ERA-EDTA (European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association) Registry.

Background: Racial disparities in kidney transplantation in children have been found in the United States, but have not been studied before in Europe.

Study Design: Cohort study.

Setting & Participants: Data were derived from the ESPN/ERA-EDTA Registry, an international pediatric renal registry collecting data from 36 European countries.