Current management of symptomatic vesicoureteral reflux in pediatric kidney transplantation-A European survey among surgical transplant professionals.

BACKGROUND: Vesicoureteral reflux (VUR) is common in children and adolescents undergoing kidney transplantation (KTx) and may adversely affect allograft kidney function. METHODS: To explore the current management of symptomatic native and allograft VUR in pediatric KTx recipients, an online survey was distributed to European surgical transplant professionals. RESULTS: Surgeons from 40 pediatric KTx centers in 18 countries participated in this survey. Symptomatic native kidney VUR was treated before or during KTx by 68% of the centers (all/selected patients: 33%/67%; before/during KTx: 89%/11%), with a preference for endoscopic treatment (59%). At KTx, 90% favored an anti-reflux ureteral reimplantation procedure (extravesical/transvesical approach: 92%/8%; preferred extravesical technique: Lich-Gregoir [85%]). Management strategies for symptomatic allograft VUR included surgical repair (90%), continuous antibiotic prophylaxis (51%), bladder training (49%), or noninterventional surveillance (21%). Redo ureteral implantation and endoscopic intervention for allograft VUR were equally reported (51%/49%). CONCLUSIONS: This survey shows uniformity in some surgical aspects of the pediatric KTx procedure. However, with regard to VUR, there is a significant variation in practice patterns that need to be addressed by future well-designed and prospective studies. In this way, more robust data could be translated into consensus guidelines for a more standardized and evidence-based management of this common condition in pediatric KTx.

Non-surgical management in children with non-refluxing primary megaureter: a systematic review and meta-analysis.

BACKGROUND: Children with non-refluxing primary megaureter are mostly managed by a watchful approach with close follow-up and serial imaging. OBJECTIVES: This systematic review and meta-analysis aimed to determine whether there is sufficient evidence to support the current non-surgical management strategy in these patients. DATA SOURCES: A comprehensive search including electronic literature databases, clinical trial registries, and conference proceedings was performed. DATA SYNTHESIS METHODS: Outcomes were estimated as pooled prevalence. If meta-analytical calculations were not appropriate, outcomes were provided in a descriptive manner. RESULTS: Data from 8 studies (290 patients/354 renal units) were included. For the primary outcome, differential renal function estimated by functional imaging, meta-analysis was impossible due to reported data not being precise. Pooled prevalence for secondary surgery was 13% (95% confidence interval: 8-19%) and for resolution 61% (95% confidence interval: 42-78%). The risk of bias was moderate or high in most studies. LIMITATIONS: This analysis was limited by the low number of eligible studies with few participants and high clinical heterogeneity, and the poor quality of the available data. CONCLUSIONS: The low pooled prevalence of secondary surgical intervention and high pooled prevalence of resolution may support the current non-surgical management in children with non-refluxing primary megaureter. However, these results should be interpreted cautiously due to the limited available body of evidence. Future studies should overcome existing limitations of imaging methods by using standardized, comparable criteria and report outcome parameters in a quantitative manner. This would allow more sufficient data synthesis to provide evidence-based recommendations for clinical decision-making and counseling. SYSTEMATIC REVIEW REGISTRATION: The protocol was registered on PROSPERO under CRD42019134502.

Diagnostic and therapeutic management of vesico-ureteral reflux in pediatric kidney transplantation-Results of an online survey on behalf of the European Society for Paediatric Nephrology.

BACKGROUND: Vesico-ureteral reflux (VUR) is considered to be a risk factor for recurrent febrile urinary tract infections and impaired renal transplant survival. METHODS: An online survey supported by the European Society for Paediatric Nephrology was designed to evaluate current management strategies of VUR in native and transplanted kidneys of recipients aged <18 years. RESULTS: Seventy-three pediatric transplant centers from 32 countries contributed to the survey. All centers performed urological evaluation prior to pediatric kidney transplantation (KTx) with subsequent interdisciplinary discussion. Screening for VUR in native kidneys (30% in all, 70% in selected patients) led to surgical intervention in 78% (11% in all, 89% in selected patients) with a decided preference of endoscopic intervention over ureterocystoneostomy. Following KTx, continuous antibiotic prophylaxis was applied in 65% of the patients and screening for allograft VUR performed in 93% of selected patients. The main management strategies of symptomatic allograft VUR were continuous antibiotic prophylaxis (83%) and surgical treatment (74%) (endoscopic intervention 55%, redo ureterocystoneostomy 26%). CONCLUSIONS: This survey demonstrates the high variability in the management of VUR in pediatric KTx recipients, points to knowledge gaps, and might serve as a starting point for improving the care for patients with VUR in native and transplanted kidneys.

Extracorporeal photopheresis versus standard treatment for acute graft-versus-host disease after haematopoietic stem cell transplantation in children and adolescents.

BACKGROUND: Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of paediatric recipients. Currently, the therapeutic mainstay for aGvHD is treatment with corticosteroids. However, there is no established standard treatment for steroid-refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and reinfusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and updated in 2015. OBJECTIVES: To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT. SEARCH METHODS: We searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE (PubMed) and Embase (Ovid) databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively. SELECTION CRITERIA: We sought to include randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in children and adolescents with aGvHD after HSCT. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author. MAIN RESULTS: We identified no additional studies in the 2021 review update, so there are still no studies that meet the criteria for inclusion in this review. AUTHORS' CONCLUSIONS: The efficacy of ECP in the treatment of aGvHD in children and adolescents after HSCT is unknown, and its use should be restricted to within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone. The 2021 review update brought about no additions to these conclusions.

Extracorporeal photopheresis versus alternative treatment for chronic graft-versus-host disease after haematopoietic stem cell transplantation in children and adolescents.

BACKGROUND: Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation, occurring in 6% to 65% of the paediatric recipients. Currently, the therapeutic mainstay for cGvHD is treatment with corticosteroids, frequently combined with other immunosuppressive agents in people with steroid-refractory manifestations. There is no established standard treatment for steroid-refractory cGvHD. The therapeutic options for these patients include extracorporeal photopheresis (ECP), an immunomodulatory treatment that involves ex vivo collection of mononuclear cells from peripheral blood, exposure to the photoactive agent 8-methoxypsoralen, ultraviolet radiation and re-infusion of the processed cell product. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and first updated in 2015. OBJECTIVES: To evaluate the effectiveness and safety of ECP for the management of cGvHD in children and adolescents after haematopoietic stem cell transplantation. SEARCH METHODS: We searched the Cochrane Register of Controlled Trials (CENTRAL) (2021), MEDLINE (PubMed) and Embase databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively. SELECTION CRITERIA: We aimed to include randomised controlled trials (RCTs) comparing ECP with or without alternative treatment versus alternative treatment alone in children and adolescents with cGvHD after haematopoietic stem cell transplantation. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection. We resolved disagreements in the selection of trials by consultation with a third review author. MAIN RESULTS: We found no studies meeting the criteria for inclusion in this 2021 review update. AUTHORS' CONCLUSIONS: We could not evaluate the efficacy of ECP in the treatment of cGvHD in children and adolescents after haematopoietic stem cell transplantation since the second review update again found no RCTs. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this population will be challenging due to the limited number of eligible participants, variable disease presentation and the lack of well-defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical data are made in favour of ECP, recipients should be carefully monitored for beneficial and harmful effects. In addition, efforts should be made to share this information with other clinicians, for example by setting up registries for children and adolescents treated with ECP.

Febrile Urinary Tract Infections in Children with Primary Non-Refluxing Megaureter: A Systematic Review and Meta-Analysis.

BACKGROUND: Knowledge of the baseline risk of febrile urinary tract infections in patients with primary non-refluxing megaureter can help clinicians to make informed decisions for offering continuous antibiotic prophylaxis. OBJECTIVE: The primary objective of this systematic review was to determine the pooled prevalence of febrile urinary tract infections in patients with primary non-refluxing megaureter selected for primary non-surgical management independent of associated attributed risk factors at initial presentation in order to assess the value of continuous antibiotic prophylaxis. METHODS: MEDLINE, EMBASE, and Cochrane Controlled Trials Register electronic databases were searched for eligible studies without language and time restriction. The systematic review was carried out following the recommendations of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. (PROSPERO registration number CRD42018104752). RESULTS: Of 25 871 records, 16 studies (n=749 patients) were eligible for inclusion. The overall pooled prevalence of febrile urinary tract infections in patients with primary non-refluxing megaureter was 14.35% (95% confidence interval: 8.8-22.6). The calculated number needed to treat for patients on continuous antibiotic prophylaxis to prevent one single febrile urinary tract infection over the course of 1-2 years would be 4.3. CONCLUSION: Based on the current available evidence the use of continuous antibiotic prophylaxis for children with PM selected for primary non-surgical treatment should be taken into consideration, at least in patients with urinary outflow impairment, higher grade of ureteral dilatation, and for children in the first months of life.

Prophylactic antithrombotic management in adult and pediatric kidney transplantation: A systematic review and meta-analysis.

BACKGROUND: RGT is a major cause for early graft loss after KTx. Although evidence-based recommendations are lacking, aP is often used to prevent RGT. This systematic review aimed to determine the effectiveness and safety of aP in adult and pediatric KTx recipients. METHODS: MEDLINE, EMBASE, Cochrane Controlled Trials Register, conference proceedings, and electronic databases for trial registries were searched for eligible studies using search terms relevant to this review (April 21, 2020). The systematic review was carried out following the recommendations of the Cochrane Collaboration and the Prefered Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. RESULTS: Twelve studies comprising 2370 patients (adult = 1415, pediatric = 955) were included, of which three were RCTs. The overall risk for developing RGT was lower in the group with aP compared with the control group (RR 0.24, 95% confidence interval 0.12-0.49). The antithrombotic drugs used were heparin (7/12), acetylsalicylic acid (2/12), a combination of both (2/12), and dipyridamole (1/12) with a high variability in timing, dosing, and mode of application. Adverse effects were reported rarely, with minor bleeding as the main complication. The non-randomized studies had significant risks of bias in the domains of patient selection, confounder, and measurement of outcomes. CONCLUSION: Based on pooled analysis, aP seems to reduce the risk of RGT in KTx. However, the reliability of these results is limited, as the quality of the available studies is poor and information on adverse effects associated with aP is scarce. Additional high-quality research is urgently needed to provide sufficient data supporting the use of aP in KTx.

Current practice of antithrombotic prophylaxis in pediatric kidney transplantation-Results of an international survey on behalf of the European Society for Paediatric Nephrology.

BACKGROUND: Renal graft thrombosis (RGT) is one of the main causes for early graft loss in pediatric kidney transplantation (KTx). Despite the lack of evidence-based recommendations, antithrombotic prophylaxis (aP) is used to prevent RGT. METHODS: An online survey supported by the European Society for Pediatric Nephrology was developed to investigate the current practice of aP in pediatric KTx recipients <18 years. RESULTS: A total of 80 pediatric KTx centers from 37 countries participated in the survey. Antithrombotic prophylaxis was performed in 96% of the pediatric renal transplant centers (all/selected patients: 54%/42%). The main overall used drugs were as follows: low-molecular-weight heparin (89%), unfractionated heparin (UFH) (69%), and acetylsalicylic acid (ASS) (55%). Ten different aP management strategies were identified as follows: 51% used a single drug and 48% combined two drugs sequentially. The corresponding centers started aP predominantly within 24 hours after pediatric KTx; 51% preferred UFH for starting aP. In centers switching to a second drug (51%), this change was performed after 10 ± 6 days; of these 57% preferred ASS for maintenance aP. Reported median aP duration was 51 days (range 1-360). CONCLUSIONS: Despite the use of aP in almost all responding pediatric KTx centers, there is no uniform management strategy. Notwithstanding, UFH seems to be the preferred drug for the early post-operative period of pediatric KTx, and ASS for maintenance prophylaxis following pediatric KTx. Prospective studies are needed to further evaluate the benefits and risks of aP, preferably resulting in guidelines for the management in pediatric KTx.

Long-term health-related quality of life and psychological adjustment in children after haemolytic-uraemic syndrome.

BACKGROUND: In children after haemolytic-uraemic syndrome (HUS), little is known about long-term health-related quality of life (HRQoL) and psychological adjustment as defined by behavioural problems, depressive symptoms and post-traumatic stress symptoms. METHODS: Sixty-two paediatric patients with a history of HUS were included in this study. Medical data of the acute HUS episode were retrieved retrospectively from hospital records. Data on the clinical course at study investigation were assessed by clinical examination and laboratory evaluation. HRQoL and psychological adjustment data were measured by standardised, parent- and self-reported questionnaires. RESULTS: Haemolytic-uraemic syndrome was diagnosed at a mean of 6.5 years before the initiation of the study (standard deviation 2.9, range 0.1-15.7) years. Among the preschool children, parents reported that their child was less lively and energetic (HRQoL emotional dimension), while no increased behavioural problems were reported. In the school-age children, self- and proxy-reported HRQoL was well within or even above the norms, while increased total behavioural problems were found. The school-age children reported no increased depression scores. Also none of the children met the criteria for full or partial HUS-associated posttraumatic stress disorder. CONCLUSIONS: Healthcare providers should be particularly alert to behavioural problems in school-age children with a history of HUS and to lower HRQoL in preschool children.

Outcome after prenatal diagnosis of congenital anomalies of the kidney and urinary tract.

UNLABELLED: Congenital anomalies of the kidney and urinary tract are common findings on fetal ultrasound. The aim of this prospective observational study was to describe outcome and risk factors in 115 patients born 1995-2001. All prenatally diagnosed children were stratified into low- and high-risk group and followed postnatally clinically and by imaging at defined endpoints. Risk factors were evaluated using odds ratios. Neonatal diagnosis included pelvi-ureteric junction obstruction (n = 33), vesicoureteral reflux (n = 27), solitary mild pelvic dilatation (postnatal anteroposterior diameter 5-10 mm; n = 25), and further diagnosis as primary obstructive megaureter, unilateral multicystic dysplastic kidney, renal dysplasia and posterior urethral valves. In 38 children with prenatal isolated hydronephrosis, ultrasound normalized at median age of 1.2 years (range 0.1-9). Surgery was performed in 34 children at median age of 0.4 years (0.1-10.8). Persistent renal anomalies without surgery were present in 43 children and followed in 36 for median time of 16 years (12.2-18). Oligohydramnios and postnatal bilateral anomalies were significantly associated with surgery and impaired renal function. CONCLUSION: The majority of children had a favourable postnatal outcome, in particular children with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis. Oligohydramnios and postnatal bilateral anomalies were risk factors for non-favourable outcome. WHAT IS KNOWN: • In congenital anomalies of the kidney and urinary tract significantly poorer outcome is known in patients with bilateral renal hypoplasia or solitary kidney associated with posterior urethral valves. • Other factors as proteinuria and vesicoureteral reflux were associated with a higher risk of progression to chronic renal failure in these patients. What is New: • Unlike other studies giving us above-mentioned information, we included all patients with any kind of prenatally diagnosed congenital anomalies of the kidney and urinary tract. Our study shows long-term follow up (median 16 years, range 12.2-18 years), especially in patients not needing surgery, but with persistent anomalies. • During postnatal long-term follow up (median 2.2 years, range 0.1-18 years) one third each showed normalization, need of surgery or persistence of anomalies without need of surgery. Our study revealed a good prognosis in the majority of these children, in particular with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis, and revealed oligohydramnios and postnatal bilateral anomalies as risk factors for a non-favourable outcome, defined as need of surgery, persistent anomalies with impaired renal function, end stage renal failure or death.

Health-related quality of life and mental health in parents of children with hemolytic uremic syndrome.

BACKGROUND: Little is known about health-related quality of life (HRQoL) and mental health of parents having children with a history of hemolytic uremic syndrome (HUS). METHODS: This study included 63 mothers and 58 fathers of a cohort of 63 HUS-affected children. At assessment, the mean time since a child experienced an acute episode of HUS was 6.4 years. Parental HRQoL, mental health and posttraumatic stress disorder (PTSD) were assessed with standardized self-report questionnaires. Medical data were extracted from patients' hospital records. RESULTS: The HRQoL and mental health of both the mothers and fathers were not impaired compared to normative data. However, a shorter time since a child's acute HUS episode was a significant predictor of lower HRQoL among the mothers, while no such effect was found among the fathers. Two fathers (3%), but no mothers, met the criteria for a diagnosis of HUS-related full PTSD; one father (2%) and four mothers (6%) met the criteria for a diagnosis of HUS-related partial PTSD. CONCLUSIONS: Our study shows that most parents of our study sample were doing well in terms of HRQoL and mental health, although a small number met the criteria for full or partial PTSD diagnosis due to their child's HUS. We therefore recommend that healthcare providers pay special attention to parents regarding PTSD symptoms during the clinical follow-up of a HUS-affected child since some parents may benefit from psychological support.

Neurodevelopmental long-term outcome in children after hemolytic uremic syndrome.

BACKGROUND: To investigate the long-term neurodevelopmental outcome in children after hemolytic uremic syndrome (HUS) and to compare outcome dependent on central nervous system (CNS) involvement during HUS. METHODS: A single-center retrospective cohort of 47 children was examined at a median age of 10.6 (range 6-16.9) years and a median follow-up of 7.8 (range 0.4-15.3) years after having had HUS. Intellectual performance was assessed with the German version of the Wechsler Intelligence Scale 4th version and neuromotor performance with the Zurich Neuromotor Assessment (ZNA). The occurrence of neurological symptoms during the acute phase of HUS was evaluated retrospectively. RESULTS: Mean IQ of the whole study population fell within the normal range (median full scale IQ 104, range 54-127). Neuromotor performance was significantly poorer in the domains "adaptive fine," "gross motor," "static balance" (all p < 0.05) and "associated movements" (p < 0.001); only the "pure motor" domain was within the normal reference range. Neurological findings occurred in 16/47 patients (34 %) during acute HUS. Neurodevelopmental outcome was not significantly different between children with or without CNS involvement. CONCLUSIONS: Our follow-up of children after HUS showed a favorable cognitive outcome. However, neuromotor outcome was impaired in all study participants. Neurological impairment during acute HUS was not predictive of outcome.