Ann Raes

• PhD
• Medical Doctor at Ghent University

Three-weekly 4-h hemodialysis/hemodiafiltration (HD/HDF) per week has become the "standard HD/HDF" regimen in children across the globe, although increasingly criticized, since crucial determinants such as residual kidney function and patient preferences are not considered. As a consequence, several children fail to achieve adequate dialysis while...

Background Patient engagement has become increasingly important in drug development, yet structured guidance to engage children (2–11 years old), adolescents (12–17 years old), and young adults (18–24 years old) is lacking. This study aims to create a matrix tool to foster paediatric patient engagement in drug development by hosting a multistakehol...

Enuresis has a complex pathophysiology involving nocturnal polyuria, reduced bladder capacity at nighttime, and impaired arousability. Desmopressin has long been used as a treatment. However, approximately 30% of children do not fully respond to it, suggesting the involvement of other factors. Solute handling and osmotic excretion have been studied...

Background/aims Due to a lack of standard pediatric prescribing information, medicines are often used in a dosage form or for an indication that has not been investigated in children. Pediatric clinical trial research networks aim to facilitate the timely availability of innovative drugs for children by developing standardized trial facilitation an...

Over the last 20 years, pediatric hypertension (pHTN) prevalence in Western society has risen from 3.5 to 9% due to childhood overweight, obesity, and secondary kidney and cardiological conditions. Few studies have assessed commonly used antihypertensive medication lisinopril’s (ACE-inhibitor) long-term efficacy and the long-term value of renin–ang...

To promote improved trial design in upcoming randomized clinical trials in childhood chronic kidney disease (CKD), insight in the within- and inter-patient variability of uremic toxins with its nutritional, treatment- and patient-related confounding factors is of utmost importance. In this study, the within- and inter-patient variability of a selec...

Background/Aims Still 60% of drugs used in children are off label. Although the EMA regulation, increased largely the timely submission of Pediatric Investigational plans (PIP) and initiation of clinical trials (CT), the majority of these CT’s remained unsuccessful due to insufficient recruitment, administrative burden, inadequate methodology, amon...

Research Objectives Informal networking with colleagues, including teachings of vast evolving novel technologies within pharmacometrics, has been identified as essential in all stages of a paediatric and pharmacology career. Young researchers have expressed the need to gain knowledge and information from peers and colleagues through a community pla...

Purpose: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE. Materials and methods: A randomized, controlled...

This study evaluated parenting stress, anxiety, and depression symptoms and their associated factors in parents of children with chronic kidney disease (CKD). This cross-sectional study compared parents of patients with CKD (0–18 years) with a matched control group of parents of healthy children. Both groups completed the Parenting Stress Index – S...

Background Nocturnal enuresis is generally considered a children's condition, yet it may persist 1%–2% in adolescence and early adulthood. Refractory patients often demand follow‐up by multidisciplinary teams, which is only restricted to some of the expert tertiary centers. However, there are no standardized transition programs/guidelines when foll...

Introduction Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is the presence of a chronic proinflammatory state, presumed to be partly driven by the accumulation of uremic toxins. In this study, we assessed the association between...

Introduction Overactive bladder (OAB) is a prevalent urological condition characterized by urinary urgency, with or without urgency urinary incontinence, accompanied by increased daytime frequency and nocturia. However, the current definition of OAB lacks a specified time frame, hindering our understanding of the temporal aspects and transitions th...

Introduction The high failure rate of industry-driven pediatric clinical trials leads to insufficient timely labeling of drugs in children and a lack of scientific evidence, resulting in the persistently high off-label drug use. National clinical trial networks can facilitate collaboration between sites, investigators, and experts, increasing the l...

Paediatric clinical trials are critical to ensure that medications prescribed to children are safe and effective. However, evidence-based dosing and labelling of such medications remain limited, and most clinical trials in paediatrics fail. Factors for lack of trial completion include performance at site level (limited patient recruitment, limited...

Background Little is known about the time-varying determinants of kidney graft failure in children. Methods We performed a retrospective study of primary pediatric kidney transplant recipients (<18 years) from the Eurotransplant registry (1990-2020). Piece-wise exponential additive mixed models were applied to analyze time-varying recipient, donor...

Aims Lisinopril, an angiotensin‐converting enzyme inhibitor, is a frequently prescribed antihypertensive drug in the paediatric population, while being used off‐label under the age of 6 years in the USA and for all paediatric patients globally. The SAFEPEDRUG project (IWT‐130033) investigated lisinopril pharmacokinetics in hypertensive paediatric p...

Introduction This article delves into the intricate relationship between kidney function, diuresis, and lower urinary tract symptoms (LUTS) throughout the transitions of the human lifespan. It explores circadian regulation of urine production, maturation of renal function from birth to adulthood, and effects of aging on kidney function and LUTS. Th...

Background This study evaluated stress, anxiety and depression symptoms and their associated factors in parents of children with chronic kidney disease (CKD). Methods This cross-sectional study compared parents of CKD patients (0–18 years) with a matched control group of parents of healthy children. Both groups completed the Parenting Stress Index...

Background: Lisinopril, an angiotensin-converting enzyme inhibitor (ACEi), is a frequently prescribed antihypertensive drug in the pediatric population, while being used off-label under the age of 6 years in the US and for all pediatric patients globally. The SAFEPEDRUG project (IWT-130033) investigated lisinopril pharmacokinetics in hypertensive p...

Introduction Due to the Paediatric Regulation in 2007, the number of paediatric clinical trials within Europe has substantially increased. Consequently, potential sites for paediatric clinical trials were overrun by trial opportunities, infrastructure pressure and their limited experience. To support sites and facilitate research, the pan-European...

Introduction Due to an increase in multicentric paediatric clinical trials after 2007 following the EU Paediatric Regulation, there has been a substantial increase in the number of feasibility questionnaires (FQ). Paediatric clinical trial conduct has made unique advances through the conect4children (c4c) pan-European network, funded by the Innovat...

Background This cross-sectional study investigated quality of life (QoL) and illness-related parental stress in children with kidney diseases by (1) comparing mean levels of these two variables between several kidney disease categories; (2) exploring correlations between QoL and parental stress; and (3) describing which disease category reports low...

Introduction Standard urotherapy in children with nocturnal enuresis (NE) is first-line treatment according to the current International Children’s Continence Society (ICCS) guidelines. ICCS defines standard urotherapy as information and demystification, instruction in how to resolve lower urinary tract dysfunction, lifestyle advice, registration o...

Background: Nocturnal polyuria (NP) due to a suppressed vasopressin circadian rhythm is a well-documented pathogenetic mechanism in enuresis, mainly studied in monosymptomatic enuresis. A substantial percentage of patients do not respond to desmopressin. This suggests that NP may not only be related to vasopressin, but that other kidney components...

Background: Catch-up growth after pediatric kidney transplantation (kTx) is usually insufficient to reach normal adult height. We aimed to analyze the effect of pre-transplant recombinant human growth hormone (rhGH) and corticosteroid withdrawal on linear growth in the first year after kidney transplantation and identify factors associated with fi...

Background Fruit and vegetable intake is commonly discouraged in children with chronic kidney disease (CKD) to avoid hyperkalemia. However, direct evidence in support of this widespread practice is lacking. Furthermore, the resultant restricted fiber exposure may deprive CKD patients from potential health benefits associated with the latter. Theref...

The COVID-19 pandemic and associated quarantine measures highly impacted parental psychological well-being. Parents of children with chronic diseases might be specifically vulnerable as they already face multiple challenges to provide adequate care for their child. The research questions of the current study were twofold: (a) to examine whether par...

Background Children with chronic kidney disease (CKD) have a low quality of life (QoL). The PedsQL™ 4.0 Generic Core Scales are widely used to assess general QoL in children. The aim of this cross-sectional study was to translate the original version of the CKD-specific PedsQL™ 3.0 End Stage Renal Disease Module into a Dutch version and to evaluate...

Background: Little is known about the relationship between sleep disruption due to nocturnal bladder emptying and Quality of Life in patients with spinal cord injury. Aim: The aim of this study was to evaluate the possible influence of number of nocturnal bladder emptying, bladder emptying method and nocturnal incontinence on the Quality of Life...

Population Pharmacokinetic (PK) model of lisinopril based on the results of the clinical trial within SAFEPEDRUG consortium.

Acute neonatal hyperammonemia is associated with poor neurological outcomes and high mortality. We developed, based on kinetic modeling, a user-friendly and widely applicable algorithm to tailor the treatment of acute neonatal hyperammonemia. A single compartmental model was calibrated assuming a distribution volume equal to the patient’s total bod...

Introduction Scarce data is available in literature about the upper urinary tract outcomes of patients with Exstrophy-Epispadias Complex (EEC). After bladder closure during childhood, EEC bladders can become hostile to the upper tracts after bladder by exposing them to high pressures, leading to hydronephrosis (HN) and kidney damage. Similarly, ves...

Kidney transplantation is universally recognized as the gold standard treatment in patients with End-stage Kidney Disease (ESKD, or according to the latest nomenclature, CKD stage 5). Robot-assisted kidney transplantation (RAKT) is gradually becoming preferred technique in adults, even if applied in very few centra, with potentially improved clinic...

Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim of this study was to investigate th...

Background: Hyperparathyroidism persists in up to 50% of pediatric kidney transplant recipients. The aims of this study were to describe the evolution of parathyroid hormone (PTH) in the first year after transplantation and to identify factors associated with hyperparathyroidism. Methods: This retrospective study included children who underwent...

Introduction & background: Despite adequate management, 20% of children with overactive bladder (OAB) syndrome fail to improve their bladder function. To approach the need for alternative strategies, an inpatient bladder rehabilitation 'voiding school' program was established. Objective: The objective of this study was to evaluate the short- and...

Background Chronic kidney disease (CKD) in children is a pro-inflammatory condition leading to a high morbidity and mortality. Accumulation of organic metabolic waste products, coined as uraemic toxins, parallels kidney function decline. Several of these uraemic toxins are protein-bound (PBUT) and gut-derived. Gut dysbiosis is a hallmark of CKD, re...

Introduction: Kidney transplantation (KT) is the gold-standard treatment for end-stage renal disease (ESRD) in children. Robot-assisted kidney transplantation (RAKT) in adults is becoming increasingly common with potentially improved morbidity compared with open KT. The study objective was to evaluate feasibility and outcomes of RAKT in children....

Background: Haemodiafiltration (HDF) is accepted to effectively lower plasma levels of middle molecules in the long term, while data are conflicting with respect to the additive effect of convection on lowering protein-bound uraemic toxins (PBUTs). Here we compared pre-dialysis β2-microglobulin (β2M) and PBUT levels and the percentage of protein b...

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort (n = 170) by comparing these with healthy and non-dia...

Background This study aims to investigate the evolution and factors associated with TAC IPV and its impact on patient outcomes in pediatric LT recipients. Methods This is a retrospective study including 41 children. The TAC IPV was expressed as the coefficient of variation and was calculated for years 1‐5 following LT. The number of missed clinic...

Shigatoxin‐associated hemolytic uremic syndrome (STEC‐HUS) is associated with significant mortality and morbidity. Case fatalities are often associated with severe neurological involvement in children and advanced age in adults but specific treatment is currently unavailable. Plasma exchange (PE) could theoretically enable removal of Shigatoxins, p...

Resistance rates for ciprofloxacin, which is labeled for treating complicated urinary tract infections in children, are rapidly rising. As there is limited knowledge on developmental pharmacology of ciprofloxacin, the primary aim of this study was to develop a population pharmacokinetic model for ciprofloxacin in children treated for complicated ur...

CYP3A enzymes are involved in the metabolism of calcineurin inhibitor tacrolimus as well as vitamin D. In this review, we summarize the clinical aspects of CYP3A-mediated metabolism of tacrolimus and vitamin D with emphasis on the influence of single-nucleotide polymorphisms on tacrolimus disposition. We describe the utility of 4β hydroxycholestero...

Objectives: To assess health-related quality of life (HRQoL) across three renal replacement therapy modalities (preemptive transplant, non-preemptive transplant, and dialysis) in comparison with the healthy norm and other chronic health conditions, and to explore related patient factors. Study design: All prevalent end-stage renal disease (ESRD)...

Diarrhea-associated hemolytic uremic syndrome (HUS) is usually associated with shigatoxin-producing Escherichia coli or shigella infections. We report 2 cases of HUS, respectively, caused by salmonella and Campylobacter jejuni infections. None of these bacteria produce shigatoxins, and the underlying mechanism of HUS development remains unknown. In...

Conclusion: The efficacy of eculizumab in STEC-HUS could not be established nor disproven based on current data, and there is a desperate need for randomized controlled trials. What is known? • Eculizumab has been used in complicated cases of Shigatoxin-associated hemolytic uremic syndrome but the efficacy remains unknown? What is new? • Eculizuma...

Conclusion: A subgroup of patients in nephrotic syndrome has a decrease in glomerular filtration, apparently related to hypovolemia which likely can be detected by a urinary potassium to potassium plus sodium ratio > 0.5-0.6 suggesting benefit of albumin infusion in this subgroup. What is Known: • Volume status can be difficult to assess based on...

Background: Little is known about the occurrence of nocturnal polyuria in spinal cord injured (SCI) patients and the definitions which are preferable in this population. Aim: To determine the occurrence of nocturnal polyuria (NP) in spinal cord injured patients during in-patient rehabilitation in the Ghent University Hospital. To study the influ...

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,...

Context Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary kidney disease. Hypophosphatemia was demonstrated in adult patients with preserved renal function, together with high fibroblast growth factor 23 (FGF23) and low soluble Klotho levels. The latter explained the relative FGF23 hyporesponsiveness in this cohort....

Background Chronic kidney disease (CKD) in childhood is characterised by the accumulation of uraemic toxins resulting in a multisystem disorder that has a negative impact on quality of life. Childhood CKD is predominantly defined by a decrease in glomerular filtration rate, estimated (eGFR) by a single serum measurement of endogenous biomarkers, e....

Background: Chronic kidney disease (CKD) in childhood is poorly explained by routine markers (e.g. urea and creatinine) and is better depicted in adults by other uraemic toxins. This study describes concentrations of representative uraemic toxins in non-dialysis CKD versus healthy children. Methods: In 50 healthy children and 57 children with CK...

A 4-year-old girl with diarrhea-associated hemolytic uremic syndrome (D+HUS) was transferred to the PICU of our center due to deteriorating renal function and neurological involvement. On admission, a comatous child was seen with hypoventilation and she was placed on mechanical ventilation. Hemodialysis was commenced but plasma exchange was discont...

The use of calcineurin inhibitors (CNIs) and vitamin D deficiency may contribute to the pathogenesis of post-transplant bone disease. CNIs and 1,25-dihydroxyvitamin D₃ (1,25(OH)2D3) are substrates of the drug-metabolizing enzyme CYP3A4. This review summarizes the indications for the use of activated vitamin D analogs in post-transplant care and the...

Background: Information on the epidemiology of Acute Kidney Injury (AKI) in children is scarce. We performed a single center retrospective cohort study to analyze the incidence of AKI, the male/female ratio, the underlying etiology, and age at presentation. We also aimed to assess outcome measured by mortality, duration of PICU stay, and developmen...

Diarrhea-associated hemolytic uremic syndrome (D+HUS) is a common thrombotic microangiopathy during childhood and early identification of parameters predicting poor outcome could enable timely intervention. This study aims to establish the accuracy of BUN-to-serum creatinine ratio at admission, in addition to other parameters in predicting the clin...

Purpose To describe the structural and functional characteristics of oxalate retinopathy, an entity described in only 40 cases until now. Methods Five patients with molecularly confirmed primary hyperoxaluria type 1 were subjected to multimodal retinal imaging (spectral-domain optical coherence tomography, white light, and HRA multispectral imagin...

Purpose: To evaluate nocturnal urine production and circadian rhythms of renal functions (glomerular filtration, water and solute diuresis) in adults with a spinal cord injury compared to controls. Materials and methods: This prospective observational study was conducted in Ghent University Hospital, Belgium. Participants were asked to perform a...

Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) encompasses a group of disorders characterized by renal tubular and interstitial abnormalities, leading to slow progressive loss of kidney function requiring dialysis and kidney transplantation. Mutations in UMOD, MUC1, and REN are responsible for many, but not all, cases of ADTKD. We re...

Objective There is a high comorbidity between nocturnal enuresis, sleep disorders and psychological problems. This study investigates whether a decrease in nocturnal diuresis volume not only improves enuresis, but also ameliorates the major comorbidities : disrupted sleep and (neuro)psychological dysfunction. Study design In this open-label, prosp...

Introduction: Children with urinary tract disorders managed by teams, or individual pediatricians, urologists, nephrologists, gastroenterologists, neurologists, psychologists, and nurses at some point move from child-centered to adult-centered health systems. The actual physical change is referred to as the transfer whilst the process preceding th...

A 12-year-old Congolese girl presented with acute renal failure, edema, hypertension, hemoptysis, hematuria, and proteinuria after a history of throat infection. Renal ultrasound showed kidneys of normal size, with increased echogenicity of the cortical parenchyma and decreased corticomedullary differentiation. Other additional investigations showe...

Background: There is a high comorbidity between nocturnal enuresis, sleep disorders and psychological problems. The aim of this study was to investigate whether a decrease in nocturnal diuresis volume not only improves enuresis but also ameliorates disrupted sleep and (neuro)psychological dysfunction, the major comorbidities of this disorder. Met...

Background: Aortic dilation and dissection contribute highly to the increased mortality of Turner syndrome (TS) but the exact pathophysiology is not completely understood. Design: Prospective case - control study. Methods: 15 prepubertal TS girls (median age 10.64, IQ 8.31-11.04) with a tricuspid (TAV, n=9) or a bicuspid (BAV, n=6) aortic valv...

The aim of the study was to identify factors associated with 1,25(OH)2D3 concentrations in liver transplant recipients with emphasis on the renal function and catabolism. We also tested the hypothesis that tacrolimus increases 1,25(OH)2D3 concentrations. Serum 25(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 were measured in 41 patients before, at 2 weeks a...

Purpose: To describe the structural and functional characteristics of oxalate retinopathy. Methods: Five patients with molecularly confirmed primary hyperoxaluria (PH) Type 1 underwent multimodal retinal imaging (spectral-domain optical coherence tomography, white light, and HRA multispectral imaging) and functional testing, including color visi...

Background: The aim of the study was to analyze the incidence of hypertension in pediatric liver transplant (LT) recipients using ambulatory blood pressure measurements (ABPM) and to identify factors associated with hypertension. We also investigated if hypertension or tacrolimus pre-dose concentration (TAC C0) were associated with increased left...

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. This...

Background: There is a growing evidence for autoimmunity in acute central nervous system (CNS) disorders and treatment with therapeutic plasma exchange (TPE) may be considered. The aim was to share our experience on the clinical application of TPE in these disorders and to present a reproducible protocol which can be used even in small children....

A 10-year-old boy presented to the emergency department with complaints of a fever, vomiting and abdominal pain in the right abdominal lower quadrant. The McBurney's and psoas signs were positive. An ultrasound of the abdomen revealed hydronephrosis, pyelitis and diffuse pyelonephritis of the right kidney. A CT scan of the abdomen showed infiltrati...

Over the past 15 years, significant progress has been made regarding the evaluation and management of lower urinary tract dysfunctions. Dysfunctional voiding plays an important role in pediatric functional voiding problems and may present with urinary tract infection, incontinence, or a variety of other symptoms including frequency, urgency, and co...

Conclusions • OnabotulinumtoxinA is a safe and effective treatment for therapy resistant OAB in non-neuropathic children. • It can be a useful treatment option for therapy resistant incontinence and/or enuresis. • With one single treatment, over 50% cure rate may be achieved in a therapy resistant patient population. • The aim of this study is to a...

Although nocturnal polyuria in monosymptomatic enuresis (MNE) can largely be explained by the decreased nocturnal vasopressin secretion hypothesis, other circadian rhythms in the kidney also seem to play a role. Recently we documented an absent day/night rhythm in a subgroup of desmopressin (dDAVP) -refractory patients. The aim of this study was to...