Urology - Summer 2011

Febrile UTIs: Shifting Paradigms?

Michael C. Carr, MD, PhD

A 3-month-old female is evaluated by her pediatrician due to fevers that have persisted for 48 hours. She appears listless and lethargic and is not feeding well, according to her mother.

spring11-figure1Given these findings, you recommend the family take her to the emergency department to obtain blood work and a urine culture. She has an elevated WBC=19.6 and her BUN/Cr=9/0.5. You speak to the ED staff and recommend she be admitted and placed on broad spectrum IV antibiotics and IV fluids.

Ampicillin and ceftriaxone are given but her spiking fevers persist for the first 36 hours of admission and slowly improve over the course of the next 24 hours. A renal and bladder ultrasound is performed showing mild dilation of the left renal pelvis. (See Figure 1.)

Discussion: It may seem obvious what the diagnosis is (pyelonephritis) and how to proceed with this evaluation. In fact, there is renewed controversy on what is the appropriate evaluation. The traditional approach has been to obtain a voiding cystourethrogram (VCUG) study to look for the presence of vesicoureteral reflux (VUR). This is a congenital condition that predisposes one to pyelonephritis if a great enough colony count of bacteria is present in the bladder. Cystitis can be due to a host of factors, but these factors may not be readily apparent in a 3-month-old. The presence of reflux provides an anatomic explanation for why pyelonephritis occurs. Furthermore, instituting antibiotic prophylaxis has been felt to lessen the chance that another febrile urinary tract infection will occur.

The management of VUR has been evolving ever since the International Reflux Study was conducted in the early 1980s. The goals of reflux management are to prevent pyelonephritic scarring and ultimately the risk of hypertension or end-stage renal disease. Factors of importance are the age and sex of the patient, presentation, degree of reflux, bladder abnormalities, and underlying renal abnormalities. Increasingly, DMSA renal scans have been used to look for renal scarring or to confirm the presence of pyelonephritis.

In the past few years, the use (or overuse) of antibiotics has been scrutinized, with concerns over the emergence of antibiotic-resistant strains. Several recent studies have shown that in randomized, perspective evaluations, antibiotic prophylaxis may not prevent the recurrence of urinary tract infections. The data has been compelling, such that the National Institutes of Health sponsored the RIVUR study, in which children who had a febrile urinary tract infection and vesicoureteral reflux were randomized to antibiotic prophylaxis or placebo. This multi-institutional study recently completed the enrollment of 800 patients and the outcome is eagerly anticipated.

The patient initially described was begun on ampicillin and cefuroxime. Her urine culture grew greater than 100,000 E. coli which was resistant to ampicillin, but sensitive to all other antibiotics. She was switched to Bactrim after 48 hours of IV antibiotics to complete a 10-day course and had a VCUG study after she had been afebrile for 24 hours.

slide11-figure2The American Academy of Pediatrics has been finalizing new guidelines in the diagnosis and management of febrile UTIs in infants and children between the ages of 2 and 24 months. If the ultrasonogram is normal, no further radiographic evaluation is recommended. Families are counseled on the importance of seeking medical care for future fevers to assure timely treatment of UTIs. The earlier detection of a UTI and prompt institution of antibiotics have been instrumental in minimizing the effects of ascending infections.

The patient in question was found to have evidence of left Grade III vesicoureteral reflux (see Figure 2), along with complete bladder emptying. Based upon the new AAP guidelines, if her initial US had been normal, then a VCUG study would not have been obtained. With the findings of mild pelviectasis, she did have the VCUG study, and her reflux was detected. This family was counseled on the meaning of VUR, the traditional approach of the use of antibiotic prophylaxis and the need to repeat a renal ultrasound in 1 year to document appropriate renal growth.

Several recently published studies have reported on the use of DMSA scans. The scans are obtained shortly after the presentation of the febrile UTI and 6 months later. The persistence of parenchymal scarring has been noted 18% to 37% of the time. This finding has reinforced that not all patients who have been diagnosed with pyelonephritis will develop parenchymal injury. Therefore, it is incumbent to identify the population at risk for scarring who also has reflux. Whether the use of antibiotic prophylaxis is necessary to prevent another febrile urinary tract infection may ultimately be answered by the RIVUR study.

Please refer to www.chop.edu/urology for the new guidelines on the evaluation and management of an infant with a febrile UTI. Recognize that there will be ongoing evaluation of the guidelines and determination of their effectiveness to ensure that patients are being managed optimally.

References and Suggested Readings
Conway P, et al. Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA 2007;298:179-186.

Hewitt I, et al. Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials. Pediatrics 2008;122:486-490.

Pecile P, et al. Age-related renal parenchymal lesions in children with first febrile urinary tract infections. Pediatrics 2009;124:23-29.

Pediatric Stone Disease

Sarah M. Lambert, MD

A healthy 12-year-old female in Bucks County developed severe right flank pain that resolved spontaneously after 2 hours. Two weeks later, she developed recurrent severe right flank pain associated with persistent emesis and was evaluated by a local emergency department. Intravenous hydration and pain medication were administered. A CT scan of the abdomen and pelvis demonstrated a 7 mm distal right ureteral calculus with dilatation of the proximal collecting system. Her pain and nausea were controlled, and she was discharged to follow up with CHOP Urology.

She was evaluated in our Pediatric Stone Center 4 days later and had been asymptomatic during this period. We counseled the child and her family about renal colic. She had no personal or family history of kidney disease or nephrolithiasis. She was prescribed tamsulosin, an alpha blocker, to facilitate stone passage and asked to strain her urine. Her family was instructed to return to the Emergency Department if she developed uncontrolled pain, nausea, or fever, as a urinary tract infection in the setting of a ureteral calculus can result in urosepsis. After 2 weeks, she returned to CHOP Urology with a renal and bladder ultrasound that demonstrated a persistent right ureteral calculus.

After 3 to 4 weeks, she had failed conservative management and operative intervention was warranted. The child was taken to the operating room and a right ureteral stent was placed. She was then discharged home to return in 2 weeks for definitive stone removal, allowing for passage dilation of the ureter. She tolerated the stent well and returned to the OR in 2 weeks. Ureteroscopy was performed and the stone was identified in the distal right ureter with surrounding edema. Laser lithotripsy and basket stone extraction were performed with removal of the calculus. A right ureteral stent was left in place for 2 weeks due to the surrounding edema. The child returned to the OR 2 weeks later for stent removal. Following stent removal, a 24-hour urine collection was obtained to determine the predisposing factors. This collection demonstrated low volume and low urinary citrate. Accordingly, she was instructed to increase her water intake and begin drinking lemonade to increase the urinary citrate. This instruction is especially important during the summer months with increased fluid losses. The child has been followed with a repeat ultrasound and has been stone free. She will return to our center for a repeat 24-hour urine collection to reassess her risk factors. As nephrolithiasis is a lifelong risk, this child will continue to be followed in CHOP’s Stone Center as she progresses to adulthood.

Discussion: According to the National Institutes of Health, 1 person in 10 develops kidney stones in his lifetime. Although kidney stones are most prevalent in adults, they are on the rise in children. The Division of Urology at Children’s Hospital has seen tremendous growth in the number of children treated for stone disease. In 2000, nearly 4 children per week were evaluated and treated for stones. In 2010, the number more than doubled, to about 10 children per week. 

To meet the increasing need for specialized care for children with stone disease, we created the Pediatric Stone Center to provide multidisciplinary evaluation and management. Any child with the diagnosis of a kidney stone needs a diagnostic workup which includes imaging, laboratory studies, and a determination if medical management is warranted. Surgical intervention might ultimately be necessary. The focus of our care is twofold, treating the current stone and preventing the next one. Preventive medication is often managed in coordination with our Nephrology colleagues.

Surgical Intervention

Younger children are just as likely to need surgery as older children. Smaller stone sizes (<4 mm) are more likely to pass spontaneously, while larger stone sizes (>4 mm) are more likely to require surgery. In our program, if a kidney stone does not pass within 30 days, surgery is considered. (See Table 1.)

Table 1: Surgical Intervention Options
Procedure Treatment

Ureteroscopic stone removal / ureteroscopy

70% of cases – This procedure removes or breaks up (fragments) stones with a laser and is performed under general anesthesia on an outpatient basis. A stent is left in the ureter for a few days after treatment to promote healing and prevent blockage from swelling or spasm.

Shock wave lithotripsy

15% of cases – A mobile shock wave lithotripsy is a treatment offered to all of our patients. This procedure is used primarily for stones in the kidney or upper ureter and less than 1.5 cm in total stone burden.

Percutaneous  nephrostolithotomy

10% of cases – This surgical procedure is performed under general anesthesia; patients go home the next day without any tubes.

Laparoscopic / robotic surgery

5% of cases – This procedure requires general anesthesia. The stone is extracted through an incision in the ureter or kidney, which is then repaired in a minimally invasive setting. Most patients require overnight hospitalization.
Open Surgery Rare – CHOP has had only 1 case in more than 6 years. 

Preventing Stones

With the incidence of pediatric kidney stones on the rise, prevention has never been more important. Kidney stones develop for a variety of reasons, including genetics, anatomy, geography, medications, and underlying medical conditions. The development of stones in children has been linked to inadequate hydration, diet (for example, too much salt or protein), an inactive lifestyle, and possibly, obesity.

Parents and pediatricians need to recognize the acute symptoms of a kidney stone and understand how to care for a child over the long term. For many, kidney stones will become a chronic condition. A child who has had 1 stone has a 50% chance of developing a second; a child who has had 2 stones has a 75% chance of developing a third. To reduce the likelihood of recurrence

Gotta Go! The Child with Daytime Wetting

Amanda K. Berry, MSN, CRNP

KG is a 7-year-old girl with worsening daytime wetting. She voids 5 to 6 times each day, often with urgency, and has urine leakage associated with urgency most days and occasional soaking accidents. She moves her bowels every other day, and stools are occasionally large and firm. Her daily fluid intake consists of 2 to 3 cups of milk, 1 juice box, and sips at the water fountain in school. She has had 2 afebrile urinary tract infections in the past year with symptoms of dysuria, abdominal pain, and wetting. Her last infection was 6 weeks ago, and a recent urinalysis was normal. An ultrasound showed normal kidneys, a normal bladder, and 36 mL postvoid residual urine.

Discussion: Daytime wetting is one of the most common urologic complaints in children. Anatomic and neurologic causes of wetting are rare, and the majority of children with daytime wetting have functional or physiologic incontinence. The causes of pediatric incontinence can be broadly classified as an alteration in either the bladder storage or emptying phase of the voiding cycle. The most common etiologies of daytime wetting are summarized in Table 2.

Table 2: Characteristics of Daytime Wetting in Children
Diagnosis Cause Characteristics Initial Management Secondary Management

Overactive Bladder

Detrusor overactivity causing frequent bladder contractions Frequent, urgent voiding with posturing; wetting interspersed with dry periods Hydration, timed voiding, voiding diary Anticholinergic

Dysfunctional Voiding

Increased activity rather than relaxation of pelvic floor during voiding Prolonged or staccato flow pattern and incomplete bladder emptying Hydration, timed voiding, voiding diary Biofeedback

Underactive Bladder

Large capacity bladder with reduced contractility from longstanding voiding postponement Infrequent voiding with little urge to void; valsalva voiding with incomplete bladder emptying Timed voiding, voiding diary, double void, boys sit to void Biofeedback

Vaginal Voiding

Pooling of urine in vagina that dribbles out after voiding Dampness after voiding or on standing Toilet position, spread legs with voiding None
Giggle Incontinence Centrally mediated activation of micturition with laughter Complete bladder emptying that only occurs with laughter increase voiding frequency around activities that elicit laughter Stimulant (methylphenidate)

Conditions associated with pediatric incontinence include constipation and urinary tract infection. Direct pressure of stool on the bladder trigone increases the likelihood of spontaneous bladder contractions, while accumulation of stool in the rectum can make it difficult to relax the anterior pelvic floor muscles to empty the bladder completely. Urinary tract infection can be both a cause and effect of voiding dysfunction. Since the sequelae of infection include epithelial inflammation, infection can be the origin of some irritative bladder symptoms and altered bladder habits. The sensory and motor changes associated with these conditions can lead to voiding patterns that persist long after the underlying problem has resolved.

A detailed voiding history can provide clues to the nature of the voiding problem. The child and parent should be questioned about the child’s frequency of urination, presence of urgency or posturing to hold urine, the child’s response to urgency, quality of the urine stream, any pain or straining, and frequency and texture of bowel movements. A 3-day elimination diary is a useful tool to define the frequency and severity of incontinence episodes as well as the presence of constipation. The diary should also include an assessment of fluid intake. One should assess for social, emotional, and behavioral concerns, which may occur as a consequence of wetting or pose obstacles to effective behavioral management.

A focused physical exam includes assessment of the abdomen for signs of constipation. The lower back is inspected for sacral malformation, hairy tuft, lipoma, or asymmetry of the gluteal crease, and the coccyx is examined for evidence of sacral agenesis. Genitals are assessed for labial adhesions, vulvovaginitis, and urethral position in girls and meatal stenosis in boys. The physical exam should also include assessment of lower extremity strength, tone, and reflexes. Urinalysis is an important element of the initial evaluation of a child with wetting. In addition to screening for infection or bacteriuria, the specific gravity of a first morning urine sample is useful in evaluating urine concentrating ability, while the presence of glucose can identify diabetes mellitus.

Whether the precise cause of wetting is readily identified, initial steps in managing functional incontinence should focus on education in normal bowel and bladder function, timed voiding, adequate hydration, and aggressive management of constipation. The nature of the problem should be explained in language appropriate for the family and child so they understand the rationale for steps involved in treatment. The cornerstone of treatment is structured water drinking and timed voiding. Fluid intake must be maintained to promote regular bladder cycling. A minimum of 8 ounces of water 3 times daily stimulates a feeling of fullness, promotes regular voiding, and can decrease holding behaviors. Drinking each cup in 10 to 15 minutes promotes rapid filling of the bladder and resets the threshold for bladder recognition. Children should be instructed to urinate on waking, every 2 hours during the day, and before bed. A voiding chart can increase motivation and can be used to assess progress and compliance. These measures alone significantly improve symptoms in 30% to 50% of children.

Successful outcomes require consistency and time, and this should be explained at the outset. Challenges in managing voiding problems lie in identifying the underlying cause while minimizing unnecessary testing, taking time to educate the child and family, and supporting them through the behavior changes that may be necessary to remediate the problem.

KG was seen at the DOVE (Dysfunctional Outpatient Voiding Evaluation) Center and diagnosed with constipation and dysfunctional voiding. She had a staccato voiding pattern and incomplete bladder emptying. She was started on a water drinking regimen and timed voiding. Her constipation was managed with daily polyethylene glycol for 3 months, and biofeedback to facilitate appropriate pelvic floor relaxation and improve her bladder emptying. Her daytime urgency and wetting resolved after 3 biofeedback sessions over 4 months, and she had no recurrence of UTIs in the 18 months that followed treatment.

References and Suggested Readings
Hoebeke P, Bower W, Combs A, De Jong T, Yang S. Diagnostic evaluation of children with daytime incontinence. J Urol 2010;183:699-703.

Chase J, Austin P, Hoebeke P, McKenna P. The management of dysfunctional voiding in children: A report from the standardisation committee of the International Children’s Continence Society. J Urol 2010;183:1296-1302

Referral Information

The Division of Urology at CHOP sees patients at the Main Campus in University City and at the follow locations in the CHOP Care Network: Chalfont, Exton, and King of Prussia, Pa., and Voorhees, Princeton, and Atlantic County, N.J. To refer a patient, please call 215-590-2754. More information on our programs can be found at www.chop.edu/urology.

Children's Doctor - Urology - Summer 2011