Antonia H M Bouts

• Academisch Medisch Centrum Universiteit van Amsterdam

This study assessed HRQoL and emotional and behavioral difficulties (EBD) and associated variables in children with first onset SSNS. While relapsing steroid-sensitive nephrotic syndrome (SSNS) in children is associated with lower health-related quality of life (HRQoL), little is known about first onset. Four weeks after onset, children (2–16 years...

Objectives: Rituximab (RTX), used for treatment in paediatric immune-mediated diseases, can lead to hypogammaglobulinaemia and thus to an increased risk of infection, but data on these adverse effects in children are scarce. We aimed to describe the pharmacodynamics of RTX by time to B cell repopulation in paediatric immune-mediated diseases and t...

Background: Steroid-sensitive nephrotic syndrome (SSNS) is associated with a relapsing-remitting course that can be stressful for parents. As little is known of parental distress at the first onset of SSNS, this study aims to describe parental distress and everyday problems in mothers and fathers of a child with newly diagnosed SSNS participating...

Background: The aetiology of idiopathic nephrotic syndrome (INS) remains partially unknown. Viral infections have been associated with INS onset. Since we observed fewer first onset INS cases during the Covid-19 pandemic, we hypothesised that lower INS incidence was the result of lockdown measures. Therefore, the aim of this study was to evaluate...

Levamisole (LMS) is a small molecule used in the treatment of idiopathic nephrotic syndrome (INS). The pathogenesis of INS remains unknown, but most evidence points towards an immunological basis of the disease. Recently, LMS has been shown to increase the relapse-free survival in INS patients treated in combination with corticosteroids with relati...

Introduction: Since 2016, kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) in the Netherlands is performed without eculizumab prophylaxis. Eculizumab is given in case of posttransplant aHUS recurrence. Eculizumab therapy is monitored in the CUREiHUS study. Methods: All participating kidney transplant patients who...

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 (NOT...

Background: Severe chronic kidney disease (CKD) in children and young adults has shown to be associated with abnormal brain development, which may contribute to neurocognitive impairments. We aimed to investigate risk factors for neurocognitive impairment and investigate the relation with structural brain abnormalities in young severe CKD patients...

Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85–90% of patients attain complete remission of proteinuria within 4–6 weeks of treatment with gluco...

Background Randomized controlled trials in pediatric kidney transplantation are hampered by low incidence and prevalence of kidney failure in children. Real-World Data from patient registries could facilitate the conduct of clinical trials by substituting a control cohort. However, the emulation of a control cohort by registry data in pediatric kid...

Introduction The introduction of eculizumab has improved the outcome in patients with atypical hemolytic uremic syndrome (aHUS). The optimal treatment strategy is debated. Here we report the results of the CUREiHUS study, a 4-year prospective, observational study monitoring unbiased eculizumab discontinuation in Dutch aHUS patients after three mont...

Introduction The recurrence of proteinuria after kidney transplantation in patients with focal segmental glomerulosclerosis (FSGS) is considered proof of the presence of circulating permeability factors (CPFs). The aim of this study is to demonstrate the presence of plasma CPFs using series of in vitro assays. Methods Podocytes and endothelial cel...

(1) Background: Health-related quality of life (HRQoL) is lower in patients with chronic kidney disease (CKD) compared to the general population. In 2011, the KLIK PROM portal was implemented in the Emma Children’s Hospital to monitor and discuss HRQoL in daily care. This study describes and assesses the implementation and use of the KLIK PROM port...

Background In pediatric patients treated with levamisole to prevent relapses of idiopathic nephrotic syndrome (INS), a transient and non-progressive rise in creatinine levels has been observed. It has been suggested that levamisole affects tubular secretion of creatinine. However, other potential mechanisms — nephrotoxicity and interference with th...

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 Eculizumab is a lifesaving yet expensive drug for atypical hemolytic uremic syndrome. Current guidelines advise a fixed-dosing schedule, which can be suboptimal and inflexible in the individual patient. Methods We evaluated pharmacokinetics (PK) and pharmacodynamics (PD) (classical pathway (CP) activity levels) of eculizumab in 48 patie...

Background Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differe...

Background The pathophysiology of neurological dysfunction in severe chronic kidney disease (CKD) in children and young adults is largely unknown. We aimed to investigate brain volumes and white matter integrity in this population and explore brain structure under different treatment modalities. Methods This cross-sectional study includes 24 patie...

Background C3 glomerulopathy (C3G) is a rare kidney disorder characterized by predominant glomerular depositions of complement C3. C3G can be subdivided into dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). This study describes the long-term follow-up with extensive complement analysis of 29 Dutch children with C3G. Methods Twenty-nin...

Context: Idiopathic nephrotic syndrome (INS) in children is a disease with considerable morbidity, yet the incidence and risk for relapse have not been systematically reviewed. Objective: To estimate the overall pooled weighted incidence and risk for relapse of INS in children. Data sources: Medline and Embase (until December 2020). Study sel...

Objectives: Rituximab (RTX) is a chimeric monoclonal CD20-antibody. Lack of efficacy has been suggested to be related to the presence of anti-drug antibodies (ADA). The aims of this study were to determine if ADA impact the pharmacokinetics (PK) and pharmacodynamics (PD) of RTX in children, whether the formation of ADA differs between various immu...

Nephrotic syndrome in childhood is a common entity in the field of pediatric nephrology. The optimal treatment of children with nephrotic syndrome is often debated. Previously conducted studies have shown significant variability in nephrotic syndrome management, especially in the choice of steroid-sparing drugs. In the Netherlands, a practice guide...

Aim To compare Health‐Related Quality of Life (HRQOL) of paediatric patients with newly collected HRQOL data of the general Dutch population, explore responses to individual items and investigate variables associated with HRQOL. Methods Children (8–12y) and adolescents (13–17y) from the general population (N = 966) and from a paediatric population...

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literatu...

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...

Background: Levamisole is used as a steroid-sparing drug for the treatment of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome (INS) in children. As part of a large multicentre randomized controlled trial with levamisole, pharmacokinetic and pharmacodynamic parameters of levamisole in children with INS were investigated, as...

One of the main objectives of the European health policy framework is to ensure equitable access to high-quality health services across Europe. Here we examined country-specific kidney transplantation and graft failure rates in children and explore their country- and patient-level determinants. Patients under 20 years of age initiating kidney repla...

Introduction Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an an...

Objective. Steroid-sensitive nephrotic syndrome (SSNS) in children is often complicated by one or more relapses, as manifested by the appearance of proteinuria. Besides health-related triggers, psychological stress might be related to relapse. This longitudinal study examined the link between perceived stress, emotional valence (feeling happy vs. u...

Introduction Primary FSGS is an important cause of ESRD in children. FSGS recurrence after kidney transplantation is associated with early graft loss. No guidelines for treatment of FSGS recurrence exist. We conducted a survey to gain insight into variation of treatment between centers. Methods A survey was sent to all members of the ESPN on behal...

The necessity of post‐transplant monitoring for donor‐specific antibodies (DSAs) is unclear. This study evaluates the clinical relevance of post‐transplantation donor‐specific HLA antibodies in pediatric renal transplant recipients, aiming at better stratification of patients at risk of graft dysfunction and better recommendations for post‐transpla...

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,...

Introduction Oral corticosteroids are the first-line treatment for idiopathic childhood nephrotic syndrome. Most children experience several relapses, needing repeated courses of corticosteroid therapy. This exposes them to side effects and long-term complications. For most patients, long-term prognosis is for complete resolution of the disease ove...

Introduction Isolated antenatal hydronephrosis (ANH), defined as a dilatation of the renal pelvis (≥5mm), is one of the most common abnormalities detected on prenatal ultrasound. However, established cut-off values for postnatal follow-up differ between countries and are based on little evidence. The current protocol in the Netherlands for follow-u...

Background The role of complement in the atypical form of hemolytic uremic syndrome (aHUS) has been investigated extensively in recent years. As the HUS-associated bacteria Shiga-toxin-producing Escherichia coli (STEC) can evade the complement system, we hypothesized that complement dysregulation is also important in infection-induced HUS. Methods...

Introduction Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether ‘transition’ (the transfer from paediatric to adult care) influences cont...

We describe an 8 month old girl with diarrhea, urosepsis and hemolytic uremic syndrome caused by E. coli. Typing of cultured E. coli strains from urine and blood revealed the presence of virulence factors from multiple pathotypes of E. coli. This case exemplifies the genome plasticity of E. coli and the resulting heteropathogenic strains. Copyright

Background: The aim of this study was to develop a population pharmacokinetic model of tacrolimus in paediatric patients at least 1 year after renal transplantation and simulate individualised dosage regimens. Patients and methods: We included 54 children with median age of 11.1 years (range 3.8-18.4 years) with 120 pharmacokinetic profiles perf...

Background: Somatic mosaicism is being increasingly recognised as an important cause of non-Mendelian presentations of hereditary syndromes. A previous whole-exome sequencing study using DNA derived from peripheral blood identified mosaic mutations in DICER1 in two children with overgrowth and developmental delay as well as more typical phenotypes...

Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children. The authors analyzed clinical and histologic data of fiv...

At present, transient asymptomatic hepatitis E virus (HEV) infection is common among healthy adults in Western Europe, as reported by blood transfusion services. In immune-suppressed patients HEV infection is often without clinical symptoms, but without therapeutic intervention it may become chronic and lead to cirrhosis. This report describes the...

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Many children with end-stage renal disease (ESRD) living in Western Europe are of non-Western European origin. They have unfavourable somatic outcomes compared with ESRD children of Western origin. In this study, we compared the Health-related Quality of Life (HRQoL) of both groups. All children (5-18 years) with ESRD included in the RICH-Q project...

Impaired glomerular function is one of the health problems affecting childhood cancer survivors (CCS). It is unclear whether glomerular function deteriorates or recovers. We investigated time trends and predictors of glomerular function in CCS. We evaluated repeated observations of estimated glomerular filtration rate (GFR) and glomerular dysfuncti...

Many children receiving a kidney transplant are seronegative for CMV and therefore, highly susceptible to a primary CMV infection. This study aims at evaluating incidence, time of occurrence, and severity of CMV infection in the first year post-transplantation in relation to different types of CMV prophylaxis. Transplantations in three centers in t...

Background Children with renal diseases who are treated with glucocorticoids are at increased risk of developing osteoporosis and fractures. However, there is no common strategy for prevention of corticosteroid-induced osteoporosis. The present systematic review was performed to determine whether prevention of bone loss by calcium (Ca), vitamin D (...

The use of patient reported outcomes (PROs) in pediatric practice is effective in increasing discussion about emotional and psychosocial functioning. This finding forms the basis for implementing KLIK: a web-based program using electronic PROs (ePROs). The aim of this article is to describe the KLIK implementation in line with the 8 methodological...

Background: Evidence-based guidelines for pediatric renal transplantation (Tx) are lacking. This may lead to unwanted treatment variations. We aimed to quantify the variation in treatment policies and its consequences in daily practice in 11 centers that provide renal Tx for children in three European countries. Methods: We surveyed Tx policies...

Background and objectives Little is known about renal function and blood pressure (BP) in long-term childhood cancer survivors. This cross-sectional study evaluated prevalence of these outcomes and associated risk factors in long-term childhood cancer survivors at their first visit to a specialized outpatient clinic. Design, Setting, Participants,...

Prytula AA, Bouts AH, Mathot RAA, van Gelder T, Croes LK, Hop W, Cransberg K. Intra-patient variability in tacrolimus trough concentrations and renal function decline in pediatric renal transplant recipients. Abstract: High intra-patient variability in TCL exposure is a risk factor for allograft loss and late acute rejection. We hypothesized that a...

In Belgium and the Netherlands, up to 40% of the children on dialysis are children with immigrant parents of non-Western European origin (non-Western). Concerns exist regarding whether these non-Western patients receive the same quality of care as children with parents of Western European origin (Western). We compared initial dialysis, post-initial...

In the Netherlands and Belgium, an increasing number of children who have end-stage renal disease (ESRD) are of non-Western origin. We analysed renal transplantation practices and outcome for immigrant ESRD children as compared to native children in both countries. All Dutch and Belgian children aged <19 years who received their first renal transpl...

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Very young children with chronic kidney disease often have difficulty maintaining adequate nutrition, which contributes to the high prevalence of short stature in this population. Characteristics of the dialysis prescription and supplemental feeding via a nasogastric (NG) tube or gastrostomy may improve growth, but this is not well understood. Here...

The low prevalence of childhood end-stage renal disease and the small centre sizes have been a barrier for clinical studies and the development of evidence-based guidelines for chronic renal replacement therapy (cRRT) in children. Few data exist on the quality of care for these patients and the applicability of existing guidelines. The aim of this...

Quality improvement research strives to bridge the gap between ideal and actual care.1 Many paediatric diseases are rare, and thus there is insufficient evidence to define ‘ideal care’. Low prevalences and generally small patient numbers in centres in which children with rare diseases are treated create considerable barriers for clinical studies an...

Sirs, Spurred by the reported spectacular results of eculizumab treatment in atypical hemolytic uremic syndrome (aHUS) due to aberrations in the complement system, an increasing number of children will receive this treatment in future. The main adverse effect of this therapy is an increased susceptibility to meningococcal infection due to inhibiti...

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In spite of the overall increased renal graft survival, long-term allograft survival has remained least successful in adolescent recipients. A major change in their care is the transition from the paediatric to the adult nephrology unit. To analyse the effect of transition on the acute rejection frequency and graft survival, we performed a historic...

Kidney transplant in patients with atypical hemolytic uremic syndrome (aHUS) is associated with a poor outcome because of recurrent disease, especially in patients known to have a factor H mutation. Long-term prophylactic plasma exchange and combined liver-kidney transplant have prevented graft loss caused by recurrence. However, the mortality asso...

Forkhead box (FOXP3) is considered to be a specific marker for regulatory T cells. The aim of this study was to correlate intragraft FOXP3 at mRNA and cellular levels during renal allograft rejection to response to therapy and late clinical outcome. Immunostainings and quantitative reverse-transcriptase polymerase chain reaction for FOXP3, CD3, and...

Patients with atypical haemolytic uremic syndrome (aHUS) with a mutation in the gene encoding membrane cofactor protein (CD46) are known to have a better prognosis than those with mutations in factor H (CFH) or factor I (CFI), but a small number of the former still proceed to end-stage renal failure. Plasma therapy (PE) is the recommended approach...

Delayed graft function and acute rejections adversely affect the long-term survival of kidney transplantation. To decrease the incidences of these phenomena, we changed the initial immunosuppressive protocol in pediatric kidney transplantation in The Netherlands. We compared a cohort (n=123) treated with basiliximab and delayed onset cyclosporine (...

Kinderen die zich presenteren met een urineweginfectie en systemische infectieverschijnselen (koorts, malaise, leucocytose en CRP-stijging) worden onder verdenking van acute pyelonefritis vaak intraveneus behandeld om littekenvorming in de nier te voorkomen. Deze littekenvorming kan namelijk op lange termijn leiden tot hypertensie en verminderde ni...