Case Report: Renal artery stenosis in children: ultrasound as a decisive diagnostic and therapy-accompanying technique!

IntroductionRenal artery stenosis in children is rare, and the recommended diagnostic algorithm, including techniques such as catheter-based angiography, CT angiography, magnetic resonance angiography, and ultrasound, is controversial in pediatric cohorts.Case presentationWe report a case of an 11-year-old girl with renal artery stenosis in whom ultrasonography played a decisive role in confirming the diagnosis and accompanying therapeutic percutaneous transluminal renal artery angioplasty.ConclusionImproved ultrasound techniques and the examiner’s experience contribute to improving renal artery stenosis diagnosis in children. In particular, localized sensitive blood flow velocity analysis indicates the advantages of ultrasound compared to other imaging modalities in renal artery stenosis. Therefore, ultrasound should be a focus of future study designs addressing the search for the best diagnostic algorithm.SummaryThe advantages of ultrasound techniques in pediatric patients with renal artery stenosis compared to other imaging modalities are highlighted

Validation of attenuation imaging coefficient, shear wave elastography, and dispersion as emerging tools for non-invasive evaluation of liver tissue in children

IntroductionThe number of children with acute and chronic liver disease is rising. Moreover, liver involvement may be limited to subtle changes in organ texture especially in early childhood and some syndromic conditions, such as ciliopathies. Attenuation imaging coefficient (ATI), shear wave elastography (SWE), and dispersion (SWD) are emerging ultrasound technologies providing data about attenuation, elasticity, and viscosity of liver tissue. This additional and qualitative information has been correlated with certain liver pathologies. However, limited data are available for healthy controls and have mainly been raised in adults.MethodsThis prospective monocentric study was conducted at a university hospital with a specialization in pediatric liver disease and transplantation. Between February and July 2021, 129 children aged 0-17.92 years were recruited. Study participants attended outpatient clinics due to minor illnesses excluding liver or cardiac diseases, acute (febrile) infections or other conditions affecting liver tissue and function. ATI, SWE, and SWD measurements were performed on an Aplio i800 (Canon Medical Systems) with an i8CX1 curved transducer by two different investigators with long-standing experience in pediatric ultrasound according to a standardized protocol.ResultsConsidering multiple potential covariates, we derived percentile charts for all 3 devices relying on the Lambda-Mu-Sigma (LMS) approach. 112 children were considered for further analysis, excluding those with abnormal liver function and under-/overweight (BMI SDS<-1.96/> 1.96, respectively). Age range was 0-17.92 years (mean 6.89±0.50SD), 58% were male. The mean duration of the ultrasound examination (basic ultrasound plus SWE, SWD, and ATI) was 6.67±0.22 minutes and it was well tolerated in 83% (n=92) of cases. While ATI was related to age, SWD was found to depend on BMI SDS, and SWE on abdominal wall thickness and sex. ATI correlated with neither SWE nor SWD, but SWE was correlated with SWD.ConclusionsOur study provides norm values and reference charts for ATI, SWE, and SWD considering important covariates including age, sex and, BMI. This may help to implement these promising tools into imaging diagnostics of liver disease and to improve the diagnostic relevance of liver ultrasound. In addition, these noninvasive techniques proved to be time-effective and highly reliable, which make them ideal for application in children

International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people

These recommendations were systematically developed on behalf of the Network for Early Onset Cystic Kidney Disease (NEOCYST) by an international group of experts in autosomal dominant polycystic kidney disease (ADPKD) from paediatric and adult nephrology, human genetics, paediatric radiology and ethics specialties together with patient representatives. They have been endorsed by the International Pediatric Nephrology Association (IPNA) and the European Society of Paediatric Nephrology (ESPN). For asymptomatic minors at risk of ADPKD, ongoing surveillance (repeated screening for treatable disease manifestations without diagnostic testing) or immediate diagnostic screening are equally valid clinical approaches. Ultrasonography is the current radiological method of choice for screening. Sonographic detection of one or more cysts in an at-risk child is highly suggestive of ADPKD, but a negative scan cannot rule out ADPKD in childhood. Genetic testing is recommended for infants with very-early-onset symptomatic disease and for children with a negative family history and progressive disease. Children with a positive family history and either confirmed or unknown disease status should be monitored for hypertension (preferably by ambulatory blood pressure monitoring) and albuminuria. Currently, vasopressin antagonists should not be offered routinely but off-label use can be considered in selected children. No consensus was reached on the use of statins, but mTOR inhibitors and somatostatin analogues are not recommended. Children with ADPKD should be strongly encouraged to achieve the low dietary salt intake that is recommended for all children

Lungenfunktionsdiagnostik bei jungen Kindern : Vergleich von Impulsoszillometrie und Spirometrie

Background: Respiratory disorders are common in children. Testing pulmonary function can be useful for making a diagnosis or monitoring the therapy, when there is a prolonged disease process or a chronic lung disease. Methods for testing lung function often need complete cooperation (e.g.: spirometry) or complete inaction (sedation is often needed, e.g.: thorax compression technique). Especially in preschool children testing methods with high cooperation demands are difficult to perform. Spirometry containing computer animation of breathing maneuvers can support cooperation in infants. Impulse oscillometry (IOS) is a new method for testing pulmonary function. Impulse-type measurement signals overlay the respiratory flow and are reflected in airways and in the lung. The reflection pattern is used for analysis of pulmonary function.Patients and Methods: Pulmonary function of 368 school children (1st and 2nd class) and 112 preschool children (ps) from Aachen have been measured by spirometry (computer animation B: „flying bee between flowers“, ps-group: additionally with animation K: “candle-blowing“) and by IOS. Childrens state of health was considered (healthy, acute airway infection, chronic lung disease). The quality of measurement was assessed by different criteria. In addition to the measured values success, number of conducted mesurements and in the preschool group number of tempted measurements, duration and cooperation level was noted. Results: IOS has been performed more successful than spirometry (ps-group 88% vs. 59%). Computer animation B (spirometry) has been performed more successful compared to animation K (ps-group 59% vs. 53%). Boys (success 95%) and healthy infants (92%) have been better in doing a spirometry than girls (84%) and sick infants (87%). It must be considered that the mean age in boys was slightly higher compared to girls. Completing animation B required more time than animation K and IOS (B: 7,4±1,6 min, K: 4,2±0,8 min IOS: 4,4±0,9 min), the duration was independent from age. Cooperation level were higher in IOS compared to spirometry (IOS: 3,2±1,3; B: 2,7±1,2; K: 3±1,2). The number of tempted and conducted measurements were much higher in spirometry (B: 10,6±5,3; K: 6,8±2,9; IOS: 1,8 ± 0,8). Decreasing Age was associated with decreasing success rate more prominent in spirometry (age of 7.: 98%, age of 3.: 14%) than in IOS (age of 3: 56%). Almost all infants with a cooperation level of 1 and more performed successfully IOS, but anyway 14% of infants with the highest cooperation level of 4 failed in doing a spirometry. Cooperation level was positively correlated with increasing age. Success, cooperation, number of tempted and conducted measurements in one method was moderately correlated with the same parameters in the other method. The calculated mean values of spirometry parameters have been in normal range compared to reference values, slightly higher in healthy infants. The calculated mean values of IOS parameters (except for resonance frequency) have been in school children 12-16% below the normal range. In preschool children mean values for impedance Zrs and resistance R (5 Hz) have been 15% above the normal range, the resistance R values (10-25 Hz) 6-29% below the normal range compared to the reference valus. The larger deviation can be seen in higher frequencies. The level of correlation between the intramethodic parameters among each other is diverse. The highest correlation can be seen between FEV1 and FVC, PEF and MEF75 and between the MEF-parameters and respectively between Zrs and R5 and accordingly between Zrs and the reactance X (5 Hz). The intraindividual variation coefficient in IOS was between 6.6 and 8.8%. A correlation between IOS and spirometry can be seen slightly between Zrs, R5, X5 und FEV1 und MEF75. Considering the absolute values Zrs, R5 and X5 correlate with FVC and MEF, too. Zrs and X5 distinguish significantly between healthy infants and infants mit acute respiratroy tract infection. Children with chronic lung diseade had mean values for spirometry and X5 below and for other IOS-parameters above the normal range, the deviation was not statistical significant due to the low sample size. Conclusions: IOS is an additional and low-risk alternative for testing pulmonary function in infants, particularly for detecting obstructive ventilation disorders. Compared to spirometry IOS can be used fast and successfully with good reproducible results even in preschool children. Both ways of measuring pulmonary function provide different, but distinctive information about the airways and the lung

Table2_Validation of attenuation imaging coefficient, shear wave elastography, and dispersion as emerging tools for non-invasive evaluation of liver tissue in children.xlsx

IntroductionThe number of children with acute and chronic liver disease is rising. Moreover, liver involvement may be limited to subtle changes in organ texture especially in early childhood and some syndromic conditions, such as ciliopathies. Attenuation imaging coefficient (ATI), shear wave elastography (SWE), and dispersion (SWD) are emerging ultrasound technologies providing data about attenuation, elasticity, and viscosity of liver tissue. This additional and qualitative information has been correlated with certain liver pathologies. However, limited data are available for healthy controls and have mainly been raised in adults.MethodsThis prospective monocentric study was conducted at a university hospital with a specialization in pediatric liver disease and transplantation. Between February and July 2021, 129 children aged 0-17.92 years were recruited. Study participants attended outpatient clinics due to minor illnesses excluding liver or cardiac diseases, acute (febrile) infections or other conditions affecting liver tissue and function. ATI, SWE, and SWD measurements were performed on an Aplio i800 (Canon Medical Systems) with an i8CX1 curved transducer by two different investigators with long-standing experience in pediatric ultrasound according to a standardized protocol.ResultsConsidering multiple potential covariates, we derived percentile charts for all 3 devices relying on the Lambda-Mu-Sigma (LMS) approach. 112 children were considered for further analysis, excluding those with abnormal liver function and under-/overweight (BMI SDS 1.96, respectively). Age range was 0-17.92 years (mean 6.89±0.50SD), 58% were male. The mean duration of the ultrasound examination (basic ultrasound plus SWE, SWD, and ATI) was 6.67±0.22 minutes and it was well tolerated in 83% (n=92) of cases. While ATI was related to age, SWD was found to depend on BMI SDS, and SWE on abdominal wall thickness and sex. ATI correlated with neither SWE nor SWD, but SWE was correlated with SWD.ConclusionsOur study provides norm values and reference charts for ATI, SWE, and SWD considering important covariates including age, sex and, BMI. This may help to implement these promising tools into imaging diagnostics of liver disease and to improve the diagnostic relevance of liver ultrasound. In addition, these noninvasive techniques proved to be time-effective and highly reliable, which make them ideal for application in children.</p

Table1_Validation of attenuation imaging coefficient, shear wave elastography, and dispersion as emerging tools for non-invasive evaluation of liver tissue in children.docx

IntroductionThe number of children with acute and chronic liver disease is rising. Moreover, liver involvement may be limited to subtle changes in organ texture especially in early childhood and some syndromic conditions, such as ciliopathies. Attenuation imaging coefficient (ATI), shear wave elastography (SWE), and dispersion (SWD) are emerging ultrasound technologies providing data about attenuation, elasticity, and viscosity of liver tissue. This additional and qualitative information has been correlated with certain liver pathologies. However, limited data are available for healthy controls and have mainly been raised in adults.MethodsThis prospective monocentric study was conducted at a university hospital with a specialization in pediatric liver disease and transplantation. Between February and July 2021, 129 children aged 0-17.92 years were recruited. Study participants attended outpatient clinics due to minor illnesses excluding liver or cardiac diseases, acute (febrile) infections or other conditions affecting liver tissue and function. ATI, SWE, and SWD measurements were performed on an Aplio i800 (Canon Medical Systems) with an i8CX1 curved transducer by two different investigators with long-standing experience in pediatric ultrasound according to a standardized protocol.ResultsConsidering multiple potential covariates, we derived percentile charts for all 3 devices relying on the Lambda-Mu-Sigma (LMS) approach. 112 children were considered for further analysis, excluding those with abnormal liver function and under-/overweight (BMI SDS 1.96, respectively). Age range was 0-17.92 years (mean 6.89±0.50SD), 58% were male. The mean duration of the ultrasound examination (basic ultrasound plus SWE, SWD, and ATI) was 6.67±0.22 minutes and it was well tolerated in 83% (n=92) of cases. While ATI was related to age, SWD was found to depend on BMI SDS, and SWE on abdominal wall thickness and sex. ATI correlated with neither SWE nor SWD, but SWE was correlated with SWD.ConclusionsOur study provides norm values and reference charts for ATI, SWE, and SWD considering important covariates including age, sex and, BMI. This may help to implement these promising tools into imaging diagnostics of liver disease and to improve the diagnostic relevance of liver ultrasound. In addition, these noninvasive techniques proved to be time-effective and highly reliable, which make them ideal for application in children.</p

Prevalence of hepatitis E virus infection in pediatric solid organ transplant recipients - A single-center experience

HEV infection appears to be an emerging disease in industrialized countries. The aim of this study was to evaluate the prevalence of HEV infection in pediatric solid organ transplant recipients. One hundred and twenty‐four pediatric recipients of liver (n = 41) or kidney (n = 83) transplants aged between one and 18 yr were screened for anti‐HEV IgG antibodies. Patients were tested for fecal HEV RNA excretion if they showed anti‐HEV seropositivity. As a control group, 108 immunocompetent pediatric patients without liver disease aged between three and 18 yr were screened for anti‐HEV IgG. HEV seroprevalence was 2.4% in renal Tx (2/83), 4.9% in liver Tx patients (2/41), and 3.2% overall (4/124). Three of these four patients were HEV RNA‐negative. In one renal transplant patient, HEV genotype 3 RNA excretion persisted and liver enzymes were elevated, indicating chronic hepatitis. In the control group, eight patients (7.4%) were HEV IgG‐positive without biochemical evidence of hepatitis. The prevalence of HEV infection in pediatric renal or liver transplant recipients is not higher compared with immunocompetent children. Chronic HEV infection with long‐term carriage of the virus may develop in pediatric transplant recipients. Autochthonous HEV infection needs to be considered in uncertain cases of hepatitis in immunosuppressed as well as immunocompetent children

Perinatal Diagnosis, Management, and Follow-up of Cystic Renal Diseases A Clinical Practice Recommendation With Systematic Literature Reviews

IMPORTANCE Prenatal and neonatal cystic kidney diseases are a group of rare disorders manifesting as single, multiple unilateral, or bilateral cysts or with increased echogenicity of the renal cortex without macroscopic cysts. They may be accompanied by grossly enlarged kidneys, renal oligohydramnios, pulmonary hypoplasia, extrarenal abnormalities, and neonatal kidney failure. The prognosis is extremely variable from trivial to very severe or even uniformly fatal, which poses significant challenges to prenatal counseling and management. OBJECTIVE To provide a clinical practice recommendation for fetal medicine specialists, obstetricians, neonatologists, pediatric nephrologists, pediatricians, and human geneticists by aggregating current evidence and consensus expert opinion on current management of cystic nephropathies before and after birth. METHODS After 8 systematic literature reviews on clinically relevant questions were prepared (including 90 studies up to mid-2016), recommendations were formulated and formally graded at a consensus meeting that included experts from all relevant specialties. After further discussion, the final version was voted on by all members using the Delphi method. The recommendations were reviewed and endorsed by the working groups on inherited renal disorders of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and European Society for Paediatric Nephrology (ESPN); the German Society of Obstetrics and Gynecology (DGGG), German Society of Perinatal Medicine (DGPM), and German Society of Ultrasound in Medicine (DEGUM); and the alliance of patient organizations, PKD International. RECOMMENDATIONS The group makes a number of recommendations on prenatal and postnatal imaging by ultrasound and magnetic resonance imaging, genetic testing, prenatal counseling, in utero therapeutic interventions, and postnatal management of prenatal and neonatal cystic kidney diseases, including provision of renal replacement therapy in neonates. In addition to detailed knowledge about possible etiologies and their prognosis, physicians need to be aware of recent improvements and remaining challenges of childhood chronic kidney disease, neonatal renal replacement therapy, and intensive pulmonary care to manage these cases and to empower parents for informed decision making

Primary URECs: a source to better understand the pathology of renal tubular epithelia in pediatric hereditary cystic kidney diseases

Background In pediatric hereditary cystic kidney diseases, epithelial cell defects mostly result from rare, autosomal recessively inherited pathogenic variants in genes encoding proteins of the cilia-centrosome complex. Consequences of individual gene variants on epithelial function are often difficult to predict and can furthermore depend on the patient's genetic background. Here, we studied urine-derived renal tubular epithelial cells (URECs) from genetically determined, pediatric cohorts of different hereditary cystic kidney diseases, comprising autosomal recessive polycystic kidney disease, nephronophthisis (NPH) and the Bardet Biedl syndrome (BBS). UREC characteristics and behavior in epithelial function-related 3D cell culture were compared in order to identify gene and variant-specific properties and to determine aspects of epithelial (cell) dysfunction. Results UREC preparations from patients (19) and healthy controls (39) were studied in a qualitative and quantitative manner using primary cells cultured for up-to 21 days. In patients with biallelic pathogenic variants in PKHD1 or NPHP genes, we were able to receive satisfactory amounts of URECs of reproducible quality. In BBS patients, UREC yield was lower and more dependent on the individual genotype. In contrast, in UREC preparations derived from healthy controls, no predictable and satisfactory outcome could be established. Considering cell proliferation, tubular origin and epithelial properties in 2D/3D culture conditions, we observed distinct and reproducible epithelial properties of URECs. In particular, the cells from patients carrying PKHD1 variants were characterized by a high incidence of defective morphogenesis of monolayered spheroids-a property proposed to be suitable for corrective intervention. Furthermore, we explored different ways to generate reference cell lines for both-patients and healthy controls-in order to eliminate restrictions in cell number and availability of primary URECs. Conclusions Ex vivo 3D cell culture of primary URECs represents a valuable, non-invasive source to evaluate epithelial cell function in kidney diseases and as such helps to elucidate the functional consequences of rare genetic disorders. In combination with genetically defined control cell lines to be generated in the future, the cultivation of primary URECs could become a relevant tool for testing personalized treatment of epithelial dysfunction in patients with hereditary cystic kidney disease