Definition, diagnosis and management of fetal lower urinary tract obstruction: consensus of the ERKNet CAKUT-Obstructive Uropathy Work Group.

Fetal lower urinary tract obstruction (LUTO) is associated with high mortality and postnatal morbidity caused by lung hypoplasia and impaired kidney function. Specific diagnostic features that can guide clinical approach and decisions are lacking; thus, the European Reference Network for Rare Kidney Diseases established a work group to develop recommendations regarding the clinical definition, diagnosis and management of prenatally detected LUTO. The work group recommends the use of antero-posterior diameter of renal pelvis as the most reliable parameter for suspecting obstructive uropathies and for suspecting prenatal LUTO in the presence of fetal megacystis. Regarding prenatal and postnatal prognosis of fetuses with LUTO, the risk of fetal and neonatal death depends on the presence of oligohydramnios or anhydramnios before 20 weeks' gestation, whereas the risk of kidney replacement therapy cannot be reliably foreseen before birth. Parents of fetuses with LUTO must be referred to a tertiary obstetric centre with multidisciplinary expertise in prenatal and postnatal management of obstructive uropathies, and vesico-amniotic shunt placement should be offered in selected instances, as it increases perinatal survival of fetuses with LUTO.

Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept.

Renal dysplasia is a severe congenital abnormality of the kidney parenchyma, which is an important cause of end-stage renal failure in childhood and early adulthood. The diagnosis of renal dysplasia relies on prenatal or postnatal ultrasounds as children show no specific clinical symptoms before chronic kidney disease develops. Prompt diagnosis is important in terms of early introduction of nephroprotection therapy and improved long-term prognosis. Metabolomics was applied to study children with renal dysplasia to provide insight into the changes in biochemical pathways underlying its pathology and in search of early indicators for facilitated diagnosis. The studied cohort consisted of 72 children, 39 with dysplastic kidneys and 33 healthy controls. All subjects underwent comprehensive urine metabolic profiling with the use of gas chromatography and liquid chromatography coupled to mass spectrometry, with two complementary separation modes of the latter. Univariate and multivariate statistical calculations identified a total of nineteen metabolites, differentiating the compared cohorts, independent of their estimated glomerular filtration rate. Seven acylcarnitines, xanthine, and glutamine were downregulated in the urine of renal dysplasia patients. Conversely, renal dysplasia was associated with higher urinary levels of dimethylguanosine, threonic acid or glyceric acid. This is the first metabolomic study of subjects with renal dysplasia. The authors define a characteristic urine metabolic signature in children with dysplastic kidneys, irrespective of renal function, linking the condition with altered fatty acid oxidation, amino acid and purine metabolisms.

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

Levamisole has been considered the least toxic and least expensive steroid-sparing drug for preventing relapses of steroid-sensitive idiopathic nephrotic syndrome (SSINS). However, evidence for this is limited as previous randomized clinical trials were found to have methodological limitations. Therefore, we conducted an international multicenter, placebo-controlled, double-blind, randomized clinical trial to reassess its usefulness in prevention of relapses in children with SSINS. The efficacy and safety of one year of levamisole treatment in children with SSINS and frequent relapses were evaluated. The primary analysis cohort consisted of 99 patients from 6 countries. Between 100 days and 12 months after the start of study medication, the time to relapse (primary endpoint) was significantly increased in the levamisole compared to the placebo group (hazard ratio 0.22 [95% confidence interval 0.11-0.43]). Significantly, after 12 months of treatment, six percent of placebo patients versus 26 percent of levamisole patients were still in remission. During this period, the most frequent serious adverse event (four of 50 patients) possibly related to levamisole was asymptomatic moderate neutropenia, which was reversible spontaneously or after treatment discontinuation. Thus, in children with SSINS and frequent relapses, levamisole prolonged the time to relapse and also prevented recurrence during one year of treatment compared to prednisone alone. However, regular blood controls are necessary for safety issues.

Evaluation of the effect of 3-month bladder basic advice in children with monosymptomatic nocturnal enuresis.

INTRODUCTION: Advice (BBA) into the standards of patients' care in both monosymptomatic and non-monosymptomatic nocturnal enuresis. Although the idea of this recommendation was clear and reflects clinical experience, duration and efficacy have not been definitely established. Recent data have demonstrated the lack of efficacy of BBA and a fierce discussion has ensued. The present study was aimed to assess the efficacy of BBA in a group of previously untreated children with primary monosymptomatic nocturnal enuresis (MNE). STUDY DESIGN: The study was a prospective interventional multicenter trial in a cohort of previously untreated MNE patients. Forty-nine children (36 males, 13 females, mean age 7.2 years) were included in the analysis. The treatment efficacy was assessed at the 30th, 60th, and 90th days of BBA. RESULTS: We discovered that the mean number of wet nights decreased significantly (p < 0.001) only after 3 months of BBA from 8.9 to 5.9 episodes every 2 weeks. BBA was fully successful in 2% o the children after 30 day, 12% after 60 days, and 18% after 90 days (Figure). Partial response (by ICCS) was assessed for 8%, 20%, and 34% of the patients. We noted a relatively high rate of non-responders that decreased from 90% to 47% after 90 days. We detected no differences in BBA efficacy between children with night-time polyuria or decreased maximal voided volume. A lower number of wet nights initially predicted the response to the BBA. DISCUSSION: Our study confirmed rather limited efficacy of BBA, similarly to previous observations, but provided more information on isolated MNE, because of a more specific study group and longer period of observation. The limitation of the study was lack of randomization. CONCLUSION: Our study revealed that in treatment-naïve children with monosymptomatic enuresis basic bladder training had a low (18%) and late effect, mostly pronounced after the third month of therapy. It seems that only if the patient presents with a favorable profile of bedwetting, occasionally and with a high maximum voided volume, it is worth maintaining BBA for a longer period of up to 3 months before initiating second-line therapy. In an unfavorable initial profile desmopressin or an alarm may be introduced much earlier.

The management of childhood urinary incontinence.

The International Children's Continence Society (ICCS) has undertaken an enormous effort to standardize both the terminology and management of various aspects of incontinence in children, including enuresis, bladder overactivity, dysfunctional voiding and psychological comorbidities. A number of guidelines have been published to aid those involved in the care of children with lower urinary tract symptoms. This review addresses a number of recommended diagnostic and therapeutic strategies, including urotherapy and pharmacological treatment, with emphasis on a focused medical history, information acquired from bladder diaries and uroflow evaluations. The major role of urotherapy is underlined with supportive pharmacotherapy, when indicated. The article provides both a summary of ICCS guidelines and a brief review of recently published papers related to the contemporary management of childhood incontinence, a health issue still underestimated by both the child's caregivers and healthcare providers.

High efficacy of biofeedback therapy for treatment of dysfunctional voiding in children.

INTRODUCTION: Dysfunctional voiding is a frequent condition in children associated with symptoms of incontinence. The aim of this study was to present the efficacy of biofeedback treatment on the resolution of clinical symptoms in a large cohort of children with urodynamically confirmed dysfunctional voiding. MATERIAL AND METHODS: 81 children (75 girls and 6 boys) aged 6-18 years (mean: 10.32 ±3.17 yrs.) with a dysfunctional voiding pattern are presented. 74/81 (92.6%) of children were unresponsive to standard urotherapy and prior pharmacotherapy. Symptoms of bladder dysfunction were evaluated by questionnaire, bladder diary and an urodynamic study according to definitions and standards set by ICCS. The biofeedback training was planned for 2 months. Each session consisted of about 30 repeats of 5 s contraction and 30 s relaxation of pelvic floor muscles and external urethral sphincter. Biofeedback was performed together with standard urotherapy. RESULTS: 67 (82.72%) of the 81 children declared wetting during the day and 41 (50, 62%) - wetting during the night. 32/81 (39.5%) children had increased voiding frequency and 43 (53.08%) had decreased bladder capacity. Following 2 months of biofeedback therapy daytime incontinence resolved in 34/67 (50.7%) children and nighttime incontinence in 22/41 (53.65%). A further 40,3% declared partial improvement in daytime and 26.7% in nighttime wetting. CONCLUSIONS: Biofeedback treatment is an effective therapeutic option for children with dysfunctional voiding. Pelvic floor therapy with biofeedback should be offered to children with dysfunctional voiding resistant to standard urotherapy.

[Biofeedback treatment of giggle incontinence in a teenager]. / Zastosowanie metody biofeedback w leczeniu moczenia wywolanego smiechem.

UNLABELLED: Giggle incontinence is a rare syndrome in which apparently complete voiding occurs specifically during laughing. It needs to be differentiated from stress incontinence and detrusor instability. Reports on the treatment outcome of this disorder are rare. THE AIM OF THE STUDY: To present the effect of biofeedback treatment for giggle incontinence in a 15-year-old girl. A 15-year-old girl is presented with isolated symptoms of giggle incontinence from early childhood with 1-2 episodes per week of complete bladder emptying during laughter. She demonstrated no symptoms of detrusor hyperactivity or stress incontinence. Her urodynamic studies were normal. The child started pelvic floor muscle exercises using biofeedback according to the pediatric protocol of an UROSTYM device. Five hourly sessions were performed to teach the child control of her external urinary sphincter muscles. This was followed by daily home exercises and weekly biofeedback sessions. Improvement was immediate and during 2 months follow-up no incidents of giggle incontinence were observed. CONCLUSIONS: (1) Biofeedback can be used in children with giggle incontinence to strengthen their pelvic floor muscles and allow them to remain continent during an uncontrolled detrusor contraction provoked by laughing. (2) Biofeedback enables children to visualize the pelvic floor muscles during exercises helping them to attain better control of their function. (3) Pelvic muscle exercises with biofeedback technique are a promising additional mode of treatment for children with voiding disorders.

[Preliminary results of a program for the early management of children with congenital hydronephrosis]. / Wstepne wyniki programu wczesnej opieki nefro-urologicznej nad dziecmi z wrodzonym wodonerczem.

UNLABELLED: Antenatal hydronephrosis is one of the most frequently diagnosed congenital abnormalities in the fetus. The aim of the study is to present the preliminary results of a newly launched Pommeranian Program for Early Management of CAKUT in Children. MATERIAL AND METHODS: 105 neonates and infants with hydronephrosis were assessed between Jan and Dec 2007 (27 girls and 78 boys). All patients had postnatal ultrasound performed. Static and dynamic scyntigraphy and cystography were performed according to set indications. Therapeutic decisions were made following a team meeting between pediatric nephrologists and urologists. RESULTS: 56.2% of children with hydronephrosis had documented prenatal findings: 61%--pyelectasis, 15.3% renal cysts, 5.1% unspecified renal pathology, in 18.6% no renal pathology. 82.6% of newborns had term births but perinatal complications were observed in 30.5%. Initial postnatal diagnosis was performed by neonatal wards in 22.8% newborns and by the children's pediatrician in 31.4% of infants. Following referral to nephro-urology centre cystography was performed in 22.9% of infants and scintigraphy in 36.2%. 21.9% of infants were qualified for surgical intervention at an average age of 24 + 13 weeks. CONCLUSIONS: 1. Only half of the children with congenital hydronephrosis are to nephro-urology care following prenatal diagnosis. 2. A large number of perinatal complications are observed in newborns with prenatally diagnosed hydronephrosis. 3. The management of newborn hydronephrosis requires better cooperation between obstetricians, neonatologists, pediatric nephrologists and urologists.

[Evolving pattern of bladder dysfunction in boys with posterior urethral valves (PUV)]. / Przebieg zaburzen funcji pecherza moczowego u pacjentów z zastawka cewki tylnej na podstawie badan urodynamicznych.

UNLABELLED: Bladder dysfunction is present in 50-80% boys born with PUV. THE AIM OF THE STUDY: To assess the effect of age on the pattern of voiding dysfunction. MATERIAL AND METHODS: An analysis of urodynamic findings was performed in 62 boys with PUV divided into younger (mean 6.02 yrs) and older (mean 15.6 yrs) age groups. RESULTS: In younger boys a higher prevalence of decreased bladder compliance (p < 0.0001), detrusor instability (p < 0.001) and detrusor sphincter dyssynergy (p < 0.05) was noted. In older boys a higher prevalence of low detrusor pressure was observed (p < 0.01). CONCLUSION: The pattern of bladder dysfunction in boys with PUV evolves with age.

[Estimation of GFR from serum creatinine and cystatin C-A comparison of 2 methods in patients with neurogenic bladder due to myelomeningocle (MMC)]. / Szacowanie GFR na podstawie wartosci kreatyniny i cystatyny C--porównanie dwóch metod w grupie pacjentów z pecherzem neurogennym w przebiegu przepukliny oponowo-rdzeniowej (MMC).

UNLABELLED: Glomerular filtration rate (eGFR) calculated from serum creatinine can be overestimated in patients with muscle mass deficits. AIM: The aim of this study was to compare eGFR calculated from serum levels of creatinine and cystatin C in a group of patients with neurogenic bladder due to MMC. MATERIAL AND METHODS: GFR calculations were performed for 67 patients using Schwartz formula for creatinine measured by colorimetric method and Filler formula for cystatin C measured by immunonephelometric method. RESULTS: Statistically significant lower eGFR values were obtained with calculations based on cystatin C levels. CONCLUSION: Cystatin C is a useful marker for GFR estimations in patients with reduced muscle mass.

[Chronic renal disease in boys with posterior urethral valve]. / Przewlekla choroba nerek u chlopców z zastawka cewki tylnej.

UNLABELLED: Posterior urethral valve (PUV) is the most common anatomical cause of bladder outlet obstruction with an incidence ranging from 1/3000 to 1/8000 births. In spite of early valve ablation deterioration of renal function is frequently reported during childhood and adolescence. AIM OF THE STUDY: To evaluate the frequency and progression of chronic renal disease in boys born with PUV. MATERIALS AND METHODS: The presence of chronic renal disease (CRD) in 58 boys with posterior urethral valve (PUV) was assessed by renal ultrasound and estimation of glomerular filtration rate (GFR). GFR was estimated by the method of Schwartz. Chronic renal disease was defined according to NFK K/DOQI Guidelines and classified into 5 stages. RESULTS: 48 (82%) patients with PUV had CRD. Among the patients observed from birth 89% already demonstrated CRD in the first year of life. CONCLUSIONS: 1. The vast majority of boys with PUV (83%) demonstrate symptoms of chronic renal disease. 2. CRD in boys with PUV is frequently evident from the first year of life. 3. PUV patients require regular nephrologic assessment from birth.

[Prevalence of hyperechoic renal pyramid syndrome in neonates and infants with congenital heart disease--ultrasound study of the abdominal cavity in the years 1996-2000]. / Czestosc wystepowania zespolu hiperechogennych piramid u noworodków i niemowlat z wrodzonymi wadami serca--analiza badan ultrasonograficznych jamy brzusznej przeprowadzonych w latach 1996-2000.

UNLABELLED: The normal medullary pyramids both in children and in adults are non-echoic on ultrasound evaluation when compared with renal cortex. Hyperechoic pyramids are associated with abnormal function of renal tubules. This sonographic finding has been described in various diseases including transient renal insufficiency in neonates and hypercalciuria induced by long-term furosemide therapy. The aim of this study was to evaluate the occurrence of hyperechoic pyramids in neonates and infants with congenital heart diseases. MATERIAL AND METHODS: The examined population consisted of 350 neonates and infants (187 male - 53%, 163 female - 47%), mean age 54,9 +/- 75,7 days (range 1 - 349 days) with new recognized congenital heart disease. All renal sonographic evaluations were performed from January 1st 1996 to December 31st 2000. RESULTS: A total of 19 (5.5%) neonates had increased echogenicity of the renal medullary pyramids. Almost 2/3 of cases were diagnosed in neonates with cyanotic congenital heart diseases. In infants with congenital heart disease hyperechoic pyramids were found in 5 (1.4%) cases. CONCLUSIONS: 1. In our study was shown, that the main reason of hyperechoic pyramids syndrome was neonatal asphyxia in association with cyanotic congenital heart disease. 2. Further nephrological evaluation is necessary in all case of hyperechoic pyramids syndrome. 3. Ultrasound examination of urinary tract should be an integral part of a complex evaluation of a patient with congenital heart disease.