Comparison of the microbiological milieu of patients randomized to either hydrophilic or conventional PVC catheters for clean intermittent catheterization.

INTRODUCTION: Control of bacteriuria is problematic in patients who perform clean intermittent catheterization for management of neurogenic bladder. This population is often burdened with multiple urinary tract infections (UTIs), placing them at increased risk of end-stage renal disease. Hydrophilic catheters are a potential way to improve smooth and clean insertion, reduce disruption of the urothelium, and reduce bacterial colonization. OBJECTIVE: The goal of the study was to compare the type and virulence of microorganisms recovered from the urine of patients that use either a hydrophilic or conventional polyvinyl chloride (PVC) catheter. METHODS: Fifty patients with an underlying diagnosis of myelomeningocele were recruited for a 12-month prospective, randomized, investigator-blinded study. Twenty-five patients were allocated to the hydrophilic catheter intervention, and 25 continued use of a PVC catheter. Cultures were performed on urine obtained by catheterization at enrollment, and 3, 6, and 12 months. Bacterial species were assigned a designation as either potentially pathogenic or non-pathogenic. Escherichia coli isolates were the most predominant and were serotyped to further stratify the pathogenicity of the strains. Lastly, patients were surveyed at enrollment, and at the two later time points evaluating their current catheter for satisfaction. RESULTS: A total of 232 different bacterial isolates were obtained from the 182 collected urine cultures. In addition, seven species were recovered from the two UTI reported during the study period. Bacterial growth was not detected in 29 of the samples (16%). Although not statistically significant, collectively there was a 40% decrease in the average number of potentially pathogenic species recovered from those patients using hydrophilic catheters (0.81 per urine sample) compared with PVC catheter use (1.24 per urine sample). Since E. coli species can be either pathogenic or non-pathogenic, we examined 14 of the most commonly implicated serotypes associated with uropathogenic E. coli (UPEC). We identified the serotype of 57% of E. coli strains recovered. There was a trend for the recovery of fewer UPEC serotypes from the hydrophilic group (54% hydrophilic verses 64% PVC), further suggesting that the catheter type may influence the microbiological milieu. Although no significant differences were reported in patient satisfaction, almost half of the patients from the hydrophilic catheter cohort continue use of this type of catheter. CONCLUSIONS: There was a trend for reduced recovery of potentially pathogenic bacteria with the use of hydrophilic catheters. The reduction in potentially pathogenic species will reduce antibiotic exposures and some patients may prefer the comfort hydrophilic catheters provide.

Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract.

UNLABELLED: Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. IMPORTANCE: The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant ramifications for bacterial persistence and disease severity. While many studies have demonstrated that modifications of the LPS lipid A moiety modulate the extent of Toll-like receptor 4 (TLR4) activation, our studies implicate the O-antigen sugar moiety as another potential rheostat for the modulation of proinflammatory cytokine production.

Is VCUG still indicated following the first episode of urinary tract infection in boys?

OBJECTIVES: To determine if voiding cystourethrogram (VCUG) following first episode of urinary tract infection (UTI) offers any incremental diagnostic advantage in boys if a comprehensive renal and bladder ultrasonogram (RBUS) revealed no abnormalities. METHODS: All boys less than 10 years of age whose first evaluation for UTI included RBUS and VCUG were retrospectively studied over a 10-year period. Those with a disorder of the urinary tract known before imaging were excluded. RBUS and VCUG results were analyzed. RESULTS: Of the 77 who met the inclusion criteria, 58 (77%) were <1 year old. 45 (58%) boys had normal RBUS and VCUG. In 16 (21%) both studies were abnormal: 15 had vesicoureteral reflux (VUR) and one had posterior urethral valves. The remaining 16 (21%) had one abnormal study: 10 had pelvicaliectasis on RBUS without VUR; 6 had normal RBUS with VUR. No urethral abnormality was diagnosed on VCUG when RBUS was normal. Of the six who had VUR and normal RBUS, the one who required surgical intervention had recurrent febrile UTI. CONCLUSIONS: If a well-performed RBUS is normal in a boy with first UTI, the likelihood of a significant finding in VCUG is low. A VCUG is likewise of no apparent screening benefit for obstructive uropathy. With the uncertainties surrounding the benefit of chemoprophylaxis, omitting a VCUG when a RBUS is normal in boys with a first UTI avoids the morbidity without missing important pathologies or altering evolving management protocols.

Relationship among bacterial virulence, bladder dysfunction, vesicoureteral reflux and patterns of urinary tract infection in children.

PURPOSE: We hypothesized that virulence levels of Escherichia coli isolates causing pediatric urinary tract infections differ according to severity of infection and also among various uropathies known to contribute to pediatric urinary tract infections. We evaluated these relationships using in vitro cytokine interleukin-6 elicitation. MATERIALS AND METHODS: E. coli isolates were cultured from children presenting with urinary tract infections. In vitro cytokine (interleukin-6) elicitation was quantified for each isolate and the bacteria were grouped according to type of infection and underlying uropathy (neurogenic bladder, nonneurogenic bowel and bladder dysfunction, primary vesicoureteral reflux, no underlying etiology). RESULTS: A total of 40 E. coli isolates were collected from children with a mean age of 61.5 months (range 1 to 204). Mean level of in vitro cytokine elicitation from febrile urinary tract infection producing E. coli was significantly lower than for nonfebrile strains (p = 0.01). The interleukin-6 response to E. coli in the neurogenic bladder group was also significantly higher than in the vesicoureteral reflux (p = 0.01) and no underlying etiology groups (p = 0.02). CONCLUSIONS: In vitro interleukin-6 elicitation, an established marker to determine bacterial virulence, correlates inversely with clinical urinary tract infection severity. Less virulent, high cytokine producing E. coli were more likely to cause cystitis and were more commonly found in patients with neurogenic bladder and nonneurogenic bowel and bladder dysfunction, whereas higher virulence isolates were more likely to produce febrile urinary tract infections and to affect children with primary vesicoureteral reflux and no underlying etiology. These findings suggest that bacteria of different virulence levels may be responsible for differences in severity of pediatric urinary tract infections and may vary among different underlying uropathies.

The relationship between obesity and complications after neonatal circumcision.

PURPOSE: Penile adhesions with hidden penis and penile skin bridges are complications after neonatal circumcision that seem to develop more often in overweight children. They could possibly be avoided if there were neonatal parameters predicting circumcision complications. We hypothesized that penile adhesions with hidden penis and skin bridges may be predicted by the height and weight of a newborn. MATERIALS AND METHODS: We performed an institutional review board approved case-control study. Boys younger than 5 years who presented for evaluation of penile adhesions with hidden penis and/or penile skin bridges after newborn circumcision were compared to boys of the same age who were circumcised at birth and did not have penile adhesions with hidden penis and/or skin bridges when evaluated for cryptorchidism or hernia/hydrocele. Weight for length percentiles were compared at birth and at urological evaluation. RESULTS: We evaluated 51 patients with penile adhesions and hidden penis after newborn circumcision, and compared them to 33 age matched controls. Boys with hidden penis had a statistically higher weight for length percentile at birth and at urological evaluation. However, in boys with penile skin bridges there was no statistical difference in the weight for length percentile at either time. CONCLUSIONS: An increased weight for length percentile in male infants before and after circumcision may be associated with penile adhesions with hidden penis but not penile skin bridges. These parameters should be considered before newborn circumcision when counseling parents, and after circumcision since early recognition of obesity might indicate the need for diligent genital hygiene to try to prevent post-circumcision complications.

In vitro analysis of the bactericidal activity of Escherichia coli Nissle 1917 against pediatric uropathogens.

PURPOSE: The usefulness of prophylactic antibiotics to prevent recurrent urinary tract infections in children was recently questioned. Some groups have attempted to use probiotics, most commonly lactobacillus, to prevent recurrent infections by altering the intestinal bacterial reservoir with variable results. Mutaflor® is a possible alternative probiotic in which the active agent is Nissle 1917. Nissle 1917 is a commensal Escherichia coli strain that eradicates pathogenic bacteria from the gastrointestinal tract. Due to its ability to alter the intestinal biome we hypothesized that Mutaflor may have the potential to prevent recurrent urinary tract infections. Thus, we used an in vitro assay to analyze the effectiveness of Nissle 1917 for eradicating pediatric uropathogens. MATERIALS AND METHODS: We established a collection of 43 bacterial pediatric uropathogens. With each isolate a microcin-type assay was performed to determine the effectiveness of Nissle 1917 on bacterial growth inhibition and competitive overgrowth. RESULTS: Nissle 1917 adversely affected the growth of 34 of the 43 isolates (79%) isolates. It inhibited the growth of 21 isolates and overgrew 13. The percent of species adversely affected by Nissle 1917 was 40% for Pseudomonas, 50% for E. coli, Enterococcus and Staphylococcus, 100% for Klebsiella and Enterobacter, and 0% for Citrobacter and Serratia. CONCLUSIONS: Nissle 1917, the active agent in Mutaflor, inhibited or out competed most bacterial isolates. These mechanisms could be used in vivo to eradicate uropathogens from the gastrointestinal tract. Further study is needed to determine whether Mutaflor can prevent recurrent urinary tract infections in children.

Novel management of urinary tract infections.

PURPOSE OF REVIEW: To highlight observations that have suggested the need for changing the conventional approach to the evaluation and management of urinary tract infections (UTIs) and vesicoureteral reflux in children and examine new alternative approaches to prevention of UTI and renal scarring based on research into host-pathogen interaction. RECENT FINDINGS: Recent studies have questioned the traditional approach of using prophylactic antibiotics to prevent recurrence of UTI and development of renal scarring in children with vesicoureteral reflux. Ongoing research on host-pathogen interactions reveals a promising capability to analyze virulence factors in bacteria causing UTIs in children, identify highly virulent bacteria capable of causing pyelonephritis and renal injury, and to selectively target the gastrointestinal reservoirs of these bacteria for elimination using probiotics. SUMMARY: Promising experimental studies correlating bacterial virulence with pattern of UTI and identification and characterization of a newly available probiotic capable of eradicating uropathogenic bacteria make targeted probiotic prevention of renal injury-inducing UTIs a potential therapeutic reality.

Effect of rectal distention on lower urinary tract function in children.

PURPOSE: We investigated the effect of rectal distention on lower urinary tract function. MATERIALS AND METHODS: Children were assigned to a constipation and lower urinary tract symptoms group or to a lower urinary tract symptoms only group. The definition of constipation was based on pediatric Rome III criteria. Standard urodynamics were done initially and repeated during simultaneous barostat pressure controlled rectal balloon distention and after balloon deflation. We evaluated the effects of rectal balloon inflation and deflation on urodynamic parameters. Colonic transit time measurement, anorectal manometry and the Parenting Rating Scale of child behavior were also used. RESULTS: We studied 7 boys and 13 girls with a median age of 7.5 years who had constipation and lower urinary tract symptoms, and 3 boys and 3 girls with a median age of 7.5 years who had lower urinary tract symptoms only. Urodynamic patterns of response to rectal distention were inhibitory in 6 children and stimulatory in 12, and did not change in 8. In 54% of the cases balloon deflation reversed balloon inflation changes while in 46% balloon inflation changes persisted or progressed. No significant differences were noted in children with vs without constipation and no clinical symptom or diagnostic study predicted the occurrence, direction or degree of bladder responses. CONCLUSIONS: In almost 70% of children with lower urinary tract symptoms rectal distention significantly but unpredictably affected bladder capacity, sensation and overactivity regardless of whether the children had constipation, and independent of clinical features and baseline urodynamic findings. Urodynamics and management protocols for lower urinary tract symptoms that fail to recognize the effects of rectal distention may lead to unpredictable outcomes.

Pathogenesis of renal injury in the megabladder mouse: a genetic model of congenital obstructive nephropathy.

Congenital obstructive nephropathy (CON) is the most common cause of chronic renal failure in children often leading to end-stage renal disease. The megabladder (mgb) mouse exhibits signs of urinary tract obstruction in utero resulting in the development of hydroureteronephrosis and progressive renal failure after birth. This study examined the development of progressive renal injury in homozygous mgb mice (mgb-/-). Renal ultrasound was used to stratify the disease state of mgb-/- mice, whereas surgical rescue was performed using vesicostomy. The progression of renal injury was characterized using a series of pathogenic markers including alpha smooth muscle isoactin (α-SMA), TGF-ß1, connective tissue growth factor (CTGF), E-cadherin, F4/80, Wilm's tumor (WT)-1, and paired box gene (Pax) 2. This analysis indicated that mgb-/- mice are born with pathologic changes in kidney development that progressively worsen in direct correlation with the severity of hydronephrosis. The initiation and pattern of fibrotic development observed in mgb-/- kidneys appeared distinctive from previous animal models of obstruction. These observations suggest that the mgb mouse represents a unique small animal model for the study of CON.

Pathophysiology and management of urinary incontinence in case of distal penile epispadias.

PURPOSE: We evaluated boys with distal epispadias and urinary incontinence to determine the cause, and designed a simplified bladder neck reconstruction to restore urinary continence. MATERIALS AND METHODS: Six boys with epispadias of the glans or distal penile shaft whose incontinence persisted after successful single stage epispadias repair were evaluated with cystoscopy and urodynamics after failed attempts at toilet training. Surgical management--simplified bladder neck reconstruction--involved suprapubic excision of an identified deformity of the roof of the bladder neck and posterior urethra, followed by reapproximation of the remaining normal bladder neck and posterior urethral tissues. RESULTS: All boys displayed a characteristic deformity of the roof of the bladder neck and posterior urethra, which extended distally through the membranous urethral sphincter toward the urethral meatus. Five of the 6 boys were treated surgically, and promptly achieved normal continence and urinary control that remained durable through a mean followup of 9.6 years. Histologically, the roof deformity exhibited abnormalities including attenuation and reduction of smooth muscle. CONCLUSIONS: The meatus is not the only site involved in distal epispadias, which presents as a field defect that deforms the roof of the urethra distal to the bladder neck. Incontinence in distal epispadias has a dual etiology, namely anatomical dilatation and distortion of the bladder neck and posterior urethra, and histological abnormality of the roof tissues. These conditions combine to affect adversely coaptive and constrictive functions of the posterior urethra and urinary sphincter. Excision and reapproximation of the roof deformity appears to be proof in principle of the cause of incontinence, and offers an alternative approach to treating incontinence in these patients without the need for more invasive surgical procedures.

Requirements for accurately diagnosing chronic partial upper urinary tract obstruction in children with hydronephrosis.

Successful management of hydronephrosis in the newborn requires early accurate diagnosis to identify or exclude ureteropelvic junction obstruction. However, the presence of hydronephrosis does not define obstruction and displays unique behavior in the newborn. The hydronephrotic kidney usually has nearly normal differential renal function at birth, has not been subjected to progressive dilation and except for pelvocaliectasis does not often show signs of high-grade obstruction. Furthermore, severe hydronephrosis resolves spontaneously in more than 65% of newborns with differential renal function stable or improving. The diagnosis of obstruction in newborn hydronephrosis is challenging because the currently available diagnostic tests, ultrasonography and diuretic renography have demonstrated inaccuracy in diagnosing obstruction and predicting which hydronephrotic kidney will undergo deterioration if untreated. Accurate diagnosis of obstruction is possible but it requires an understanding of the uniqueness of both the pathophysiology of obstruction and the biology of the kidney and renal collecting system in this age group. We examine here the requirements for making an accurate diagnosis of obstruction in the young child with hydronephrosis.

Nocturnal bladder emptying for reversing urinary tract deterioration due to neurogenic bladder.

Although daytime clean intermittent catheterization with urotropic medications is often sufficient therapy to relieve urinary retention and elevated intravesical pressures, neglecting the bladder affected by neuropathy or other significant pathologies during sleeping hours can lead to overdistension of the bladder and its deleterious consequences. The effect of this seemingly inconsequential clean intermittent catheterization interlude for some patients on an ideal daytime-only management protocol can lead to a syndrome of nighttime overdistension of the bladder, which can result in recurrent urinary tract infections, worsened incontinence, decreased bladder compliance and capacity, and progressive hydroureteronephrosis and renal insufficiency. Fortunately, nocturnal bladder emptying has emerged as a specific antidote for the syndrome of nighttime overdistension of the bladder, and because nocturnal bladder emptying can reverse or prevent bladder and upper tract deterioration, it is suggested that conventional therapies performed only during the daytime may have been inadequate for certain subgroups of patients who require a new therapeutic paradigm for their optimal management.

Nocturnal bladder emptying: a simple technique for reversing urinary tract deterioration in children with neurogenic bladder.

PURPOSE: In this preliminary study we sought to determine the effect of instituting nocturnal bladder emptying (NBE) in children with neurogenic (NGB) or nonneurogenic neurogenic bladder (NNGNGB) in whom urinary tract deterioration developed despite optimal daytime clean intermittent catheterization (CIC) and urotropic medications. We hypothesize that a syndrome of nocturnal overdistention of the bladder (SNOB) can cause urinary tract deterioration through increased nighttime storage pressures manifested by recurrent urinary tract infection (UTI), worsening incontinence, hydronephrosis and/or decreasing bladder compliance and capacity, and may be reversed by NBE. MATERIALS AND METHODS: A total of 19 children with NGB (17) or NNGNGB (2) who displayed urinary tract deterioration while on CIC and urotropic medications were started on NBE. Of the patients 15 used a continuously draining nighttime catheter while 4 had scheduled awakenings during the night to perform CIC. The primary indications for NBE were recurrent symptomatic UTI in 5, new or progressive hydronephrosis in 7, and decreasing bladder capacity and compliance in 7. RESULTS: At a mean followup of 23 months 15 (79%) patients showed improvement or complete resolution of 1 or more signs or symptoms of hydronephrosis (7), increase in bladder capacity (5), recurrent UTI (6) and worsening incontinence (3). The remaining 4 patients had no response to NBE. No adverse effects were observed with 10 hours or less of nightly indwelling catheter time. CONCLUSIONS: Patients with NGB or NNGNGB on idealized daytime programs of CIC and urotropic drugs may have high intravesical pressures and experience urological deterioration because of an unrecognized SNOB. NBE is a simple technique for treating this condition and reversing the pathophysiological changes. The observation that NBE alone may increase bladder compliance and capacity sufficient to avoid bladder augmentation suggests that development of decreased bladder compliance and capacity in children with NGB may not simply represent normal progression of NGB disease. These changes may be avoidable consequences of untreated SNOB. Early institution of NBE may prevent urinary tract deterioration from developing in this population.

A novel technique for ureteral catheterization and/or retrograde ureteroscopy after cross-trigonal ureteral reimplantation.

PURPOSE: A criticism of the Cohen cross-trigonal reimplantation is the potential difficulty of retrograde access to the ureter. With the advent of modern endourological equipment, we devised a novel technique that obviates the aforementioned difficulty and permits even retrograde ureteroscopy. MATERIALS AND METHODS: Cystoscopy is performed and a curved tip vascular access catheter is directed towards the ureteral orifice. An angle tipped glide wire with a torque device attached is passed through the catheter and directed into the orifice. The combination of the curved catheter and angled glide wire permits passage of the wire in an axis perpendicular to that of the cystoscope. Once the glide wire has been passed into the proximal ureter it is exchanged for a super stiff guide wire. The latter literally straightens the ureter permitting direct retrograde passage of a catheter, stent or rigid ureteroscope. RESULTS: This technique was successful in 6 children. Of the patients 4 underwent retrograde ureteroscopy with stone extraction, 1 underwent retrograde studies followed by stent insertion and 1 underwent retrograde catheterization alone for radiographic studies. CONCLUSIONS: It is distinctly uncommon to have to access a ureter in a retrograde fashion after cross-trigonal reimplantation. However, when required the technique described reliably permits retrograde access and should dispel fears of long-term consequences of the Cohen ureteral reimplantation.

"The beneficial and protective effects of hydronephrosis".

Hydronephrosis is generally considered a pathologic process, and especially in infancy is widely viewed as caused by obstruction, potentially injurious to the kidney and in need of expeditious surgical treatment. However a number of clinical and experimental studies suggest exactly the opposite: that hydronephrosis is not pathological but actually a compensating mechanism designed to protect the kidney from high pressures and renal damage. Furthermore, because hydronephrosis in the infant involves an already compliant and distensible renal pelvis it appears to be uniquely beneficial. Herein the experimental basis for a counterargument challenging the harmful effects of hydronephrosis will be presented.

The valve bladder syndrome: pathophysiology and treatment with nocturnal bladder emptying.

PURPOSE: We determine the etiology and treat the specific pathophysiology of the valve bladder syndrome. MATERIALS AND METHODS: Defined as persisting or progressive severe hydroureteronephrosis without residual or recurrent obstruction, the valve bladder syndrome developed in 18 boys who underwent successful ablation of the posterior urethral valve. Serial radiographic, renal function, renographic, urodynamic and perfusion studies were performed for a mean time of 11 years. RESULTS: The cause of the valve bladder syndrome proved to be sustained bladder over distention due to a combination of polyuria with 24-hour urine volume greater than 2 l. in 10 boys, impaired bladder sensation in 18 and residual urine volume in 14. Treatment of over distention during the daytime alone was unsuccessful. Nocturnal bladder emptying was performed with an indwelling nighttime catheter, intermittent nocturnal catheterization and/or frequent nocturnal double voiding. Hydronephrosis markedly improved once nocturnal bladder emptying was started and was comparable to the results after urinary diversion. CONCLUSIONS: The valve bladder syndrome is not due to a permanent prenatal alteration in bladder anatomy and function. Instead, it appears to result from sustained postnatal bladder over distention due to a combination of polyuria, impaired bladder sensation and residual urine volume, which represent sequelae of prenatal valve injury. These factors synergize to prevent bladder normalization after valve ablation and progressively reduce functional bladder capacity to maintain bladder over distention. Bladder decompensation, upper tract dilation, and renal injury develop and characterize the valve bladder syndrome. Because current therapy, including intermittent catheterization, leaves the bladder full throughout the night, it remains markedly over distended. Nocturnal bladder emptying is the specific antidote for this pathophysiological situation, and results in prompt and impressive improvement or elimination of hydronephrosis in these and similar groups of patients. This response to nocturnal bladder emptying suggests that the bladder is not the primary cause for the valve bladder syndrome.