[Is there still no alternative to long-term antibacterial prophylaxis?] / Ist die antibakterielle Langzeitprophylaxe immer noch alternativlos?

In infants and children, the strategy of antibacterial long-term infection prophylaxis is more widely used in the protection against urinary tract infections (UTIs) than for hardly any other indication. Development of resistance, side effects of chemotherapeutic agents and acceptance problems require an intensive search for alternatives in the prophylaxis of UTIs. In this context, substances such as D­mannose, probiotics and herbal preparations are gaining increasing attention, whereby the effectiveness of which, especially in children, still needs proof through therapy studies. This also applies to approaches to vaccine prevention. However, prophylaxis must not be limited to the prescription of medicines. Equally important are the treatment of bladder dysfunction and constipation as well as the elimination of other predisposing factors. There are alternatives to antibiotic prophylaxis for UTIs. However, in cases with a high risk of recurrence and pyelonephritis, it is still currently the better alternative.

[Congenital dilatation of the upper urinary tract : Current diagnostic and treatment concepts]. / Konnatale Dilatationen der oberen Harnwege : Aktuelle diagnostische und therapeutische Konzepte.

Dilatations of the urinary tract are discovered in increasing numbers in intrauterine or postnatal sonographic screening examinations. Only few urinary tract anomalies (e. g. urethral valves) require immediate therapy; however, ureteropelvic stenosis and primary megaureter in particular require a prognostic classification between relevant obstructions needing correction and dilations which do not affect renal function. Ultrasound, diuresis scintigraphy and magnetic resonance imaging (MRI) remain the main pillars of advanced diagnostics despite an increasing number of biomarkers. The prevention of progressive renal parenchymal damage is the main focus of diagnostic and therapeutic strategies, while avoiding unnecessary or unnecessarily stressful interventions.

Primary non-refluxive megaureter in children: single-center experience and follow-up of 212 patients.

PURPOSE: Primary non-refluxing megaureter (pMU) is a multifaceted and challenging congenital pathology of the urinary tract. We report our 23-year experience with this anomaly in terms of presentation, diagnostic work-up and management. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 212 children diagnosed with pMU between 1986 and 2009 at our institution. Mean follow-up was 45.17 (0-192) months. RESULTS: Of the total, 168 (79 %) children presented with upper urinary tract dilation on perinatal ultrasound screening. In 44 (21 %) patients, the diagnosis was made following diagnostic work-up of a urinary tract infection (UTI, 18 %) or flank pain (3 %). In total, 203 of 254 pMUs (79.9 %) were successfully treated conservatively during the 23-year observation period. Forty-eight children (23 %) underwent ureteric reimplantation. UTIs occurred in 91 of 212 children (43 %). Of these, 41 (45 %) occurred despite antibacterial infection prophylaxis. Within the past three decades, there has been a marked shift from surgical toward conservative therapy at our institution. CONCLUSION: Neonatal renal ultrasound is the method of choice to timely identify children with pMU and, alongside dynamic renography, to monitor the clinical course. Nowadays, only a minor subset of children with asymptomatic course requires surgical correction. Antibacterial prophylaxis has the potential to reduce the risk of febrile UTIs. Prospective randomized studies are warranted to provide evidence of the beneficial effect of antibacterial prophylaxis.

[Neurogenic bladder function disorders in patients with meningomyelocele: S2k guidelines on diagnostics and therapy]. / Neurogene Blasenfunktionsstörungen bei Patienten mit Meningomyelozele : S2k-Leitlinie zu Diagnostik und Therapie.

The treatment of children and adolescents with meningomyelocele has experienced a clear change in the last 30 years. The establishment of pharmacotherapy, clean intermittent catheterization (CIC) and infection prophylaxis have improved the prognosis for patients and have led to new therapeutic strategies. The interdisciplinary cooperation between neonatologists, neurosurgeons, pediatric neurologists, pediatric urologists, pediatric nephrologists, pediatric orthopedists and pediatric surgeons leads to optimization of individualized therapy. These guidelines present definitions and classifications, investigations and timing which are described in detail. The conservative and operative therapy options for neurogenic bladder function disorders are described and discussed with reference to the current literature. The brief overview provides in each case assistance for the treating physician in the care of this patient group and facilitates the interdisciplinary cooperation.

[Primary vesicoureteral reflux]. / Primärer vesikoureteraler Reflux.

The never ending discussion about the diagnostics and treatment of vesicoureteral reflux (VUR) now includes arguments for diagnostic nihilism as well as invasive diagnostics and therapy, which is reminiscent of the debate on prostate cancer in adulthood. The common goal of all currently competing diagnostic strategies and approaches is the prevention of renal scars by the most effective and least burdensome approach. There is a difference between acquired pyelonephritic scars with VUR (acquired reflux nephropathy) and congenital reflux nephropathy (primary dysplasia) which cannot be influenced by any therapy.The VUR can be verified by conventional radiological voiding cystourethrography (VCUG), by urosonography, radionuclide cystography or even by magnetic resonance imaging (MRI). The guidelines of the European Association of Urology/European Society for Paediatric Urology (EAU/ESPU) recommend radiological screening for VUR after the first febrile urinary tract infection. Significant risk factors in patients with VUR are recurrent urinary tract infections (UTI) and parenchymal scarring and the patients should undergo patient and risk-adapted therapy. Infants with dilating reflux have a higher risk of renal scarring than those without dilatation of the renal pelvis. Bladder dysfunction or dysfunctional elimination syndrome represents a well-known but previously neglected risk factor in combination with VUR and should be treated prior to any surgical intervention as far as is possible.Certainly not every patient with VUR needs therapy. The current treatment strategies take into account age and gender, the presence of dysplastic or pyelonephritic renal scars, the clinical symptoms, bladder dysfunction and frequency and severity of recurrent UTI as criteria for the therapy decision. The use of an antibacterial prophylaxis as well as the duration is controversially discussed. Endoscopic therapy can be a good alternative to antibacterial prophylaxis or a surveillance strategy in patients with low grade VUR. In patients with dilating VUR and given indications for surgery, endoscopic treatment can be offered. However, parents should be completely informed about the significantly lower success rate of endoscopic therapy compared to open surgical procedures. The open surgical techniques guarantee the highest success rates and should be used in patients with a dilating VUR and high risk of renal damage.

[Diagnostics and therapy of urinary tract infections]. / Diagnostik und Therapie von Harnwegsinfektionen.

In infants and young children, urinary tract infections (UTI) often present with unspecific symptoms. Appropriate techniques of urine sampling play an important role for accurate microbiological diagnosis. In infants urine sampling by bladder puncture or transurethral catheter is recommended. In young infants with suspected pyelonephritis, calculated antibiotic treatment should be initiated parenterally with a combination of a third generation cephalosporin or an aminoglycoside with ampicillin. After the age of 3-6 months group 3 oral cephalosporins can be used in uncomplicated pyelonephritis. With the first febrile UTI early sonography is recommended to provide information about renal parenchymal involvement and to exclude malformations of the kidneys and urinary tract. Strategies for the recognition of vesicoureteral reflux and renal damage are under discussion. Recently published guidelines by the American Academy of Pediatrics for the diagnosis and management of UTI in febrile children and infants aged 2-24 months will most likely influence the still pending German guidelines.

[Primary megaureter]. / Primärer Megaureter.

A primary megaureter is an anomaly with a prevesical or overall dilated ureter of more than 6 mm in diameter. It is important to distinguish between cases of primary non-refluxing and primary obstructive-refluxing megaureters, as the treatment of both is completely different. The basic diagnostic work-up includes ultrasonography and voiding cystourethrography. Diuretic renography is used to detect split renal function and the degree of upper urinary tract obstruction. In most cases of primary non-refluxing megaureter surgical treatment is unnecessary due to the high remission rate, whereas obstructive refluxing megaureters commonly only need to be corrected. Antibiotic prophylaxis may be indicated in infants with a primary obstructive megaureter during the first 6 months of life due to a higher risk of complications due to pyelonephritis especially in this age group.

Children and adolescents with ureteropelvic junction obstruction: is an additional voiding cystourethrogram necessary? Results of a multicenter study.

PURPOSE: The incidence of ureteropelvic junction obstruction (UPJO) and concomitant vesicoureteral reflux (VUR) ranges from 14 to 18 %. Therefore, different guidelines recommend a voiding cystourethrogram (VCUG) to identify cases of VUR early in the diagnostic process. Aim of this multicenter study was to reassess the incidence of concomitant VUR and the need for additional VCUG in a large cohort of patients with UPJO. Furthermore, we asked for clinical objectives that defined the need for VCUG with the intention of minimizing radiation exposure and the need for invasive diagnostic procedures. METHODS: Medical records for 266 patients (69 girls, 197 boys) with UPJO were analyzed retrospectively. Data were obtained on gender, clinical symptoms, results of pre- and postnatal ultrasound, VCUG and 99(m)Technetium-MAG3 (MAG3) scan. They were correlated with the incidence of concomitant VUR. RESULTS: One hundred and seventy-eight patients (67 %) underwent VCUG. Concomitant VUR was detected in 13 patients. Dilating VUR (dVUR) was observed in 11 patients. In our study, the overall incidence of a concomitant VUR was 7.3 %. In cases of proven VUR, we observed a positive predictive value for female gender, ureteral dilatation, renal insufficiency, and recurrent urinary tract infections (UTI). But there was no correlation between concomitant VUR and the severity of hydronephrosis. CONCLUSIONS: Our data suggest that the low incidence of concomitant VUR in cases of UPJO does not justify the routine use of VCUG as a routine diagnostic tool. Especially, ureteral dilatation and recurrent UTI have a positive predictive value for concomitant VUR.

Three-year growth hormone treatment in short children with X-linked hypophosphatemic rickets: effects on linear growth and body disproportion.

CONTEXT: Children with X-linked hypophosphatemic rickets (XLH) are prone to progressive disproportionate stunting despite oral phosphate and vitamin D treatment. OBJECTIVE: Our objective was to analyze the effects of GH treatment on stature and lengths of linear body segments in short children with XLH. DESIGN, SETTINGS, AND PATIENTS: A 3-yr randomized controlled open-label GH study in short prepubertal children with XLH (n = 16) on phosphate and calcitriol treatment was conducted. A cohort of XLH patients (n = 76) on conservative treatment served as an XLH reference population. MAIN OUTCOME MEASURES: Changes in SD scores (SDS) of stature and linear body segments, i.e. sitting height, leg and arm length, and sitting height index (i.e. ratio between sitting height and stature) were the main outcome measures. RESULTS: XLH patients presented at time of enrollment with significant impairments of stature (-3.3 SDS) and linear body segments compared with healthy children. Leg length (-3.8 SDS) was most impaired, whereas sitting height (-1.7 SDS) was best preserved. The markedly elevated mean sitting height index (+3.3 SDS) reflected severe body disproportion. GH resulted in a sustained increase in linear growth (stature, +1.1 SDS; sitting height, +1.3 SDS; leg length, +0.8 SDS; arm length, +1.1 SDS; each P < 0.05 vs. baseline), whereas no significant changes were observed in controls. Mean height SDS at 3 yr did not significantly differ between groups. Sitting height index remained stable in both the GH-treated patients and in study controls but increased further in the XLH-reference population. CONCLUSIONS: The 3-yr GH treatment improved linear growth without progression of body disproportion in short children with XLH.

[Urological problems in patients with meningomyelocele. Diagnostic studies and management]. / Urologischer Erkrankungen bei Patienten mit Meningomyelozele. Diagnostik und Management.

Since the 1980s the management of children and adolescents with meningomyelocele has undergone major changes. The introduction of pharmacotherapy with antimuscarinic agents, clean intermittent catheterization (CIC) and antibacterial prophylaxis has revolutionized the management of children with neurogenic bladder. The co-operation between neonatologists, neurosurgeons, paediatric neurologists, paediatricians, paediatric urologists, paediatric nephrologists, paediatric orthopaedists and paediatric surgeons is necessary to achieve an optimized therapy in each individual patient. In this interdisciplinary consensus paper we provide definitions and classifications as well as a timetable for the appropriate investigations. The conservative and surgical options are explained in detail. A short review is given concerning orthopaedic management, incidence of latex allergy, options for bowel management, diagnosis and treatment of urinary tract infections, problems with sexuality and fertility as well as the long-term compliance of these patients and their relatives.

[Urinary tract infections in infants and children -- a consensus on diagnostic, therapy and prophylaxis]. / Harnwegsinfektionen im Säuglings- und Kindesalter. Konsensusempfehlungen zu Diagnostik, Therapie und Prophylaxe.

Urinary tract infections (UTI) are among the most common bacterial infections in infants and children. The early diagnosis of a pyelonephritis and its rapid, calculated antibacterial therapy are decisive for the prognosis. Urogenital anomalies, renal damage and bladder dysfunction may influence the risk of recurrences of UTI and pyelonephritic scarring. Diagnostic strategies therefore should focus on their early recognition. Pediatricians, urologists and infectiologists are cooperating in diagnostic, therapy and prophylaxis of UTI. The aim of the interdisciplinary consensus presented was to work out a concept which may help to manage childhood UTI in daily practice.

May we go on with antibacterial prophylaxis for urinary tract infections?

Recurrent urinary tract infections (UTIs), with or without vesicoureteric reflux (VUR), are by far the most frequent reason for long-term antibacterial prophylaxis in infants and children today. However, the strategies of antibacterial prophylaxis for the prevention of recurrent urinary tract infection are no longer universally accepted. In infants and children at risk, the benefits of antibacterial prophylaxis definitively are not yet proven by evident data. To put antibacterial prophylaxis in its place, risk groups for recurrent symptomatic infections, ascending UTI and permanent renal damage have to be defined and the efficacy of prophylaxis in these groups has to be proved by prospective randomised studies. Nevertheless, until the results of these studies are available, antibacterial prophylaxis will remain one of the most frequently practised methods to protect risk patients from pyelonephritic damage and UTI recurrences.

[Children and youths with neurogenic disturbances of bladder function. Bladder augmentation, substitution and the diversion of urine]. / Kinder und Jugendliche mit neurogener Blasenfunktionsstörung. Blasenaugmentation, Blasensubstitution und Harnableitung.

After the failure of conservative treatment in patients with neurogenic bladders, urinary diversion is a viable compromise between the urologist's concerns and the patient's desire, as the upper urinary tract can be protected in the long-term and high continence rates can be provided. This can be achieved with an acceptable complication rate. Our indications for orthotopic bladder augmentation or substitution involve patients with a good orthopedic condition and mobility, who find it easy to perform CISC through the urethra. A continent umbilical stoma offers a good alternative in obese, immobile or wheelchair bound patients. The serous lined extramural tunnel technique has proven to be superior to submucosal implantation in patients with fibrotic and dilated ureters.

Mild dehydration: a risk factor of urinary tract infection?

Bacterial growth in the urinary tract is usually prevented by host factors including bacterial eradication by urinary and mucus flow, urothelial bactericidal activity, urinary secretory IgA, and blood group antigens in secretions which interfere with bacterial adherence. Bacterial eradication from the urinary tract is partially dependent on urine flow and voiding frequency. Therefore, it seems logical to postulate a connection between fluid intake and the risk of urinary tract infections (UTIs). However, experimental and clinical data on this subject are conflicting. Experimental studies concerning the effect of water intake on susceptibility and course of UTIs were predominantly performed in the 60s and 70s. Despite many open questions, there has been no continuous research in this field. Only few clinical studies producing contradictory results are available on the influence of fluid intake concerning the risk of UTI. One explanation for the inconsistency between the data might be the uncertainty about the exact amounts of fluid intake, which was mostly recorded in questionnaires. So far, there is no definitive evidence that the susceptibility for UTI is dependent on fluid intake. Nevertheless, adequate hydration is important and may improve the results of antimicrobial therapy in UTI. Results of experimental and clinical studies concerning urinary hydrodynamics are the basis for advice given by expert committees to patients with UTI to drink large volumes of fluid, void frequently, and completely empty the bladder. The combination of the behaviourally determined aspects of host defence and not simply increasing fluid intake is important in therapy and prophylaxis of UTI.

Long-term followup of 158 young adults surgically treated for vesicoureteral reflux in childhood: the ongoing risk of urinary tract infections.

PURPOSE: We recorded urinary tract infections in the long term after surgical reflux correction. MATERIALS AND METHODS: A total of 158 of 189 patients (160 females and 29 males) who were followed in 1985, an average of 10.8 years after reflux surgery were contacted again in 1995. At that time median patient age was 26 years (range 15.7 to 38.8) and the average period of observation was 20.3 years (range 13.4 to 26). RESULTS: In 82% of the patients febrile and in 18% afebrile symptomatic urinary tract infections had developed preoperatively. In the first 10-year period after operation 46% of patients continued to have symptomatic urinary tract infections compared with 52% in the second 10-year interval. In the 2 periods the incidence of febrile urinary tract infection was about 17%. In the whole postoperative observation period symptomatic urinary tract infections developed in 66% of all patients, including 74% of female patients. Symptomatic urinary tract infections were observed during 8 of 46 pregnancies (17%). CONCLUSIONS: After successful surgical reflux correction susceptibility to urinary tract infection continues for a number of years in many girls and women. However, postoperatively urinary tract infections are primarily afebrile.

[Age-dependency of isotope drainage in diuretic renograms]. / Altersabhängigkeit des Nuklidabflusses im Diurese-Szintigramm.

OBJECTIVE: The aim of the study was to establish normal values of the isotope drainage in diuretic scintigrams for children of different age-groups. Isotope drainage was determined 30 minutes after the application of technetium- (99m)MAG 3 as well as 15 minutes after the following application of furosemide. METHODS: We analysed the data from 274 investigations in sonographically normal renal units (RU) contralateral to kidneys with ureteropelvic junction obstruction or non-refluxing primary megaureters. RESULTS: There was a significant age-dependency of isotope drainage during the first weeks of life. In 79 RU the results of the first diuretic renogramm were compared with the follow-up examinations. The reliability of the measurements was lowest in children initially investigated during the first six weeks of life. If both the investigations were performed thereafter, no significant difference was found between the results. CONCLUSIONS: The isotope drainage of the sonographically normal contralateral RU seems to be a sufficient marker for the meaningfulness of the diuretic renogram. In urinary tract dilatation, mistakes regarding the interpretation of isotope drainage may be minimized by taking the measurements in the normal contralateral RU in account and by comparing them with age-referred normal values.

GATA3 haplo-insufficiency causes human HDR syndrome.

Terminal deletions of chromosome 10p result in a DiGeorge-like phenotype that includes hypoparathyroidism, heart defects, immune deficiency, deafness and renal malformations. Studies in patients with 10p deletions have defined two non-overlapping regions that contribute to this complex phenotype. These are the DiGeorge critical region II (refs 1, 2), which is located on 10p13-14, and the region for the hypoparathyroidism, sensorineural deafness, renal anomaly (HDR) syndrome (Mendelian Inheritance in Man number 146255), which is located more telomeric (10p14-10pter). We have performed deletion-mapping studies in two HDR patients, and here we define a critical 200-kilobase region which contains the GATA3 gene. This gene belongs to a family of zinc-finger transcription factors that are involved in vertebrate embryonic development. Investigation for GATA3 mutations in three other HDR probands identified one nonsense mutation and two intragenic deletions that predicted a loss of function, as confirmed by absence of DNA binding by the mutant GATA3 protein. These results show that GATA3 is essential in the embryonic development of the parathyroids, auditory system and kidneys, and indicate that other GATA family members may be involved in the aetiology of human malformations.

Renal tubular dysgenesis (RTD) - an important cause of the oligohydramnion-sequence. Report of 3 cases and review of the literature.

Renal tubular dysgenesis (RTD) is a disorder characterized by neonatal renal failure and regular gross renal architecture, although the histological features of immature and shortened proximal tubules lead to neonatal death. The pathogenesis of this condition includes a congenital familial condition, a twin-twin transfusion syndrome, and an angiotensin-converting enzyme inhibitor intake by the mother. The clinical picture shows an association with oligohydramnia, pulmonary hypoplasia, and skull ossification defects. In the present paper, we report the occurrence of RTD in three infants of a consanguinous couple and compared our data with those of the literature. Our data confirm that late second trimester demonstration of oligohydramnion, with structurally normal kidneys and with or without skull ossification defects, allows the diagnosis of renal tubular dysgenesis, which, however, has to be confirmed by histological and immunohistological examinations of the kidney.