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No relevant financial or nonfinancial relationships COMMON PEDIATRIC UROLOGY to disclosure CONDITIONS

Kris Bonnett, ARNP Department of Urology Pediatric Urology University of Iowa Stead Family Children’s Hospital

April 16, 2019

OBJECTIVES Case

• Describe common pediatric urologic problems and • 7 year old girl with day and night incontinence which problems require further evaluation and which – Damp most days, may sometimes soak underwear are self-limiting. – Pull up soaked every night – Daytime • Understand in office evaluation and management of and frequency bladder and bowel dysfunction and urinary tract – Squats to prevent leaking infections and when to refer for further evaluation. – “Doesn’t feel the leaking until it’s too late” • Understand nocturnal and the rationale for – Diagnosed with two recent the different treatment strategies. afebrile urinary tract infections

1 4/10/19

Case (continued) Day Wetting-Prevalence

• Bowels hard, infrequently passed. • Up to 15% of primary care provider visits are • Child described as being “lazy”; waiting to the related to urinary function last minute to urinate • 2-5X more common in female patients • Child hides wet clothing • Approximately 15% of 5 – 7 year olds have • Issues regarding school enuresis rd – Peer relationships • Strong overlap in nearly 1/3 of enuretic patients – Performance with behavioral conditions – Important that both issues are addressed during treatment.

Nervous system control of Lower Urinary Tract Function of Lower Urinary Tract

• Continence involves all aspects of the nervous • STORAGE system – of adequate volumes of at low pressure and – Autonomic with no leakage • Parasympathetic – storage (pelvic nerve, S2-S4) • EMPTYING that is: • Sympathetic – emptying (hypogastric nerves, T10-L2) – Voluntary – Somatic – Efficient • External sphincter – Complete (pudendal nerve S2 – S4) – Low pressure

2 4/10/19

As the Child Grows………… Maturation of Voiding

• Bladder capacity increases & voiding frequency decreases with • Initially child has better control over external growth – Infants (<2 yo): 7 x weight (kg) = capacity (mL) sphincter than bladder – > 2 yo: capacity in ounces (30ml) = Age (yrs) + 2 – Easier to stop • Newborns with frequent, complete, low pressure emptying – Newborns void 20 x/day with only a slight decrease during the 1st year of than start it life • 1-2 yrs: conscious sensation of bladder fullness develops – Voiding inhibition done – Still immature detrusor-sphincter coordinationàfrequent voiding (10-15x by contracting external day) • 2-3 yrs: Ability to initiate or inhibit voiding voluntarily develops sphincter rather than – Inhibit micturition centrally (increasing capacity) inhibiting bladder – Initiate micturition by relaxing sphincter – Interrupt voiding by contracting sphincter contraction • >4 yrs: Voiding comes under reliable voluntary control • This pattern may be reinforced during toilet training – Adult-like pattern of micturition • Persistence of this pattern is bladder sphincter dyssynergia

Usual sequence of bowel & bladder control

• Nighttime bowel continence • Daytime bowel continence • Daytime bladder continence • Nighttime bladder continence

Normal bladder with outlet Dyssynergic bladder with relaxation during voiding outlet resistance

3 4/10/19

Possible Hypotheses for dysfunctional Age of Daytime Training elimination syndrome (DES)

• Something goes wrong during toilet training – Bladder infection – Bladder inflammation – Constipation • Interferes with bladder sensation • Impedes emptying àmechanical obstruction at bladder neck % Trained • Can induce bladder overactivity • Studies show treatment of bowel issues significantly reduce day and night wetting Months

Characterization of Dysfunctional Elimination Syndrome (DES)

ALWAYS ASK ABOUT BOWEL HABITS Storage problem vs Emptying problem • Failure to store normal • Failure to empty volumes of urine at low completely on command, pressure & without efficiently at low leakage pressures – Non compliant bladder – Failure of neurological – Irritable bladder control of bladder – Inadequate sphincter tone – Bladder muscle failure during filling – Failure of sphincter relaxation during voiding

4 4/10/19

Clinical problems from Dysfunctional Major Dysfunctional Elimination Elimination Syndrome (DES)

• Increased bladder pressures can result in • Hinman Syndrome – Secondary vesicoureteral reflux – Non-neurogenic neurogenic bladder – Kidney damage, – Acquired process with – Bladder hypertrophy leading to bladder failure NO identified • Residual Urine neurologic issue. – Urinary tract infection – Incontinence, large post void residual, • Incontinence UTI’s, upper tract – Social consequences damage – Associated with bowel dysfunction as well

Description of Types of Incontinence Dysfunction Elimination: Key history points

Classification of daytime wetting (functional ) and key distinguishing symptoms Type Key Symptoms • New or present since infancy? Urge Incontinence () • Urge • Frequency – more than 7x/day • Can child remain dry for short periods of time? • Small volume voided • History for UTI Voiding postponement • Infrequent micturition – less than 5x/day • Postponement • Voiding pattern (frequency, urgency, staccato Dysfunctional Elimination • Straining to initiate and during micturition stream • Interrupted stream of urine • Wetting during coughing, sneezing • Holding maneuvers • Small volumes • Bowel function Giggle incontinence • Wetting during laughing • Large volumes with apparently complete emptying Detrusor underactivity • Interrupted stream • Emptying of bladder possible only by straining.

5 4/10/19

Physical Examination Diagnostic Studies

• Abdominal palpation • Urinalysis, urine culture – Constipation, masses • Ultrasound of kidneys AND bladder • Spine examination/Neurological examination – Pre and post void images – Sacral dimple, hairy tuft, skin discoloration • Elevated post void if > 2 mL/kg – Back pain, leg pain/numbness/tingling, change in leg – Thickened bladder wall strength/gait • Inspection of genitalia • KUB, if necessary, for constipation – Erythema • Consider voiding cystourethrogram especially if – Pooling of urine – vaginal voiding febrile urinary tract infection – Labial adhesions/meatal stenosis • Consider MRI of lumbar spine

Urinalysis –mode of collection Determining which urine test

• Mode of collection-important to prevent Urinalysis/Microscopic Urine Culture overtreating contaminated specimens • Rapid screening for UTI • Standard for diagnosing – urine bag--least invasive, high false-positive rates • Considered complementary UTI (85-99%), only helpful if urine is negative test for UTI diagnosis for – Mid stream clean catch--need to be toilet trained, most patients non-invasive, higher chance of contamination as • AAP guidelines consider compared to catheterization urinalysis a necessary – Urethral catheterization or suprapubic aspiration — diagnostic tool in patients recommended by AAP for children < 24 months 2-24 months.

6 4/10/19

Most useful Urine Dipstick results Urine Microscopy

Leukocyte Esterase Nitrite • Pyuria is assessed with microscopy from centrifuged urine by using threshold of 5 WBC/hpf (10 WBC’s/hpf • Released when WBC are broken • Urinary nitrite is reduced down more accurate predictor in children < 2 years) • Marker for pyuria – presence of from dietary nitrates in the WBC’s in urine presence of gram-negative • Urine micro for WBC’s alone not more accurate than • False-positive bacteria – Other causes of inflammation in urine dipstick for leukocyte esterase • Distinguish asymptomatic • Gram-positive organisms • bacteriuria from true UTI will give false-negative Disadvantages – increased expense, need for • Absence of pyuria in child with a laboratory to perform, increased time to results true UTI is rare • and • Retrospective study, 2,700 children dilute urine can provide • Value of urine microscopy compared to the urine – 88% and 79% sensitivity and 96% and dipstick remains to be determined. 97.5% specificity in dilute and false negative results concentrated respectively in identifying UTI • Sensitivity is poor, • Bacteria on microscopy is most reliable and most specificity is high—positive rapid test for diagnosis of UTI nitrite test likely true UTI

Urine Culture Urinary tract infection

• Positive urine culture is essential in diagnosing UTI • Invasion of the urinary tract by an organism that • A UTI on voided sample characterized by 100,000 leads to pathologic changes cfu/mL of a single uropathogen, (based on early-AM voided urine in adult women) • Presence of urinary or constitutional symptoms, • 2011 AAP guidelines suggested for 2-24 month old along with urinalysis findings consistent with children inflammation, or bacteria on gram stain, and – 50,000 cfu/mL of single organism + pyuria and/or bacteriuria single bacterial organism on urine culture. on urinalysis from catheterized sample • Upper tract () vs lower tract • Contamination considered in low colony counts and cultures with heavy mixed growth, & cultures with (cystitis) nonpathogenic organisms-such as lactobacillus, coag- – Pyelonephritis: Fever, vomiting, flank pain, lethargy neg staph, alpha-hemolytic strep, candida species – Cystitis: afebrile, , urgency, frequency

7 4/10/19

Asymptomatic bacteriuria Radiologic Imaging to do or wait?

• Growth on two consecutive urine cultures of • Debate on appropriate imaging after first febrile more than 100,000 cfu/mL of the same UTI in a child uropathogen in a patient with no symptoms of – Historically a renal/bladder ultrasound (US) and infection. voiding cystourethrogram (VCUG) were completed • Unclear as to cause of urinary tract colonization – Lack of evidence supporting routine use of imaging in decreasing long term sequelae of pyelonephritis such • No screening needed as renal scarring or renal insufficiency • No treatment needed • Not at increased risk for recurrent UTI’s, renal damaged or impaired renal growth.

Renal and Bladder Ultrasound (RBUS) Renal and Bladder Ultrasound (RBUS)

• Show size, shape and presence of both kidneys • Additional indications • 15% RBUS done after first UTI in infants will yield – Recurrent febrile or afebrile UTI’s abnormal results – Non-E coli UTI – Undiagnosed congenital abnormalities, urinary tract obstruction, hydronephrosis, stone, fluid collections-renal or – Hypertension perirenal abscesses • Low sensitivity for detection of vesicoureteral • AAP guidelines recommend RBUS in all children < 2 yo reflux who have a febrile UTI. • • If child not responding appropriately to treatment for Low sensitivity for renal scarring compared to UTI within 48 hours or is unusually ill, RBUS should be nuclear medicine testing. performed during the acute episode

8 4/10/19

Ultrasound Voiding Cystourethrogram (VCUG)

• Standard imaging for detection and grading vesicoureteral reflux • Can also evaluate bladder size and shape, smoothness of bladder wall, urethral abnormalities • Can also identify constipation or spinal defect • Obtain after treatment completed and asymptomatic • Disadvantages include invasive test and radiation exposure

Voiding Cystourethrogram (VCUG) Voiding Cystourethrogram

• AAP guidelines do not recommend routine VCUG Reflux Bladder diverticulum Reflux, spinning top after first febrile UTI in child < 24 months unless RBUS is abnormal. • AAP Section on Urology disagree with withholding VCUG after first febrile UTI. – Some children do benefit from early detection and treatment to prevent recurrent infection/renal damage • May be difficult to determine this is the first febrile UTI • Family history for VUR • VCUG considered in older children with recurrent UTI’s especially if family history of VUR

9 4/10/19

Treatment of Dysfunctional Elimination Treatment of Dysfunctional Elimination Syndrome Syndrome

• Treat constipation aggressively • Avoid bladder irritants • Timed voiding schedule – caffeine, sports drinks, carbonated beverages, chocolate, • Treat UTI’s with narrow spectrum antibiotics when possible spicy foods, artificial sweeteners, some fruits and their – if febrile empirically start antibiotics pending urine culture juices (oranges, lemons, pineapple) • Treat for 7 - 14 days (inconclusive that longer course better) • Advanced therapies • E-coli most common uropathogen, 80% infections in children – Nitrofurantoin or a 1st generation cephalosporin often narrow-spectrum choice – Pelvic floor physical therapy & biofeedback– pediatric » Nitrofurantoin with poor tissue penetration—do not use for febrile UTI/pyelonephritis trained – TMP-SMX and amoxicillin used about 50% of time however have high e-coli resistance rates – Anticholinergic (Oxybutynin) - reduce bladder contractions, – Neonates and young infants cover for Enterococcus as higher rate of increase capacity enterococcus infections st – α-blockers (Tamsulosin) - antagonize smooth muscle in • Ampicillin or 1 generation cephalosporin bladder neck (off label use) – Nitrofurantoin with increased risk of hemolytic anemia in < 3 month old infants – β3 receptor agonists (Mirabegron) - bladder wall relaxation – TMP-SMX contraindicated in < 6 week old infants and preemies (not FDA approved in children) – Afebrile cystitis: 2-4 days is not inferior to a 7-14 day course

Clinical Pearls for Dysfunctional Elimination When to refer Dysfunctional Elimination Syndrome

• 15% of 5 year old with enuresis, 15% have • Continuous, primary incontinence that occurs day spontaneous resolution each year and night • Children with day and night enuresis are treated • Constipation refractory to therapies differently than children with just night wetting • Persistent daytime symptoms despite conservative • Children with day and night wetting should have therapies bowel and daytime bladder function addressed • Incontinence that is new after a period of > 6 months prior to treating night wetting. of dryness and positive neurological findings • Meatal stenosis • Primary interventions are typically conservative with behavioral modifications. • Labial adhesions – Can try Premarin - side effects of estrogen exposure.

10 4/10/19

Clinical Pearls for urinary tract infections When to Refer Urinary Tract Infection

• S/S in infant can be vague and non-specific • Recurrent afebrile/febrile UTI’s – Keep UTI as differential diagnosis for febrile infant • UTI’s not responsive to initial antibiotic therapy • UTI’s more common in girls except during first year of life when boys are at higher risk • Febrile UTI in an infant • Uncircumcised boys <6 months of age are 10x more • Abnormal RBUS and/or VCUG likely to have UTI than circumcised boy • Prenatally known or postnatally diagnosed • True UTI requires bacteriuria and symptoms congenital genitourinary anomaly • Increasing incidence of pyelonephritis and delay in – Postnatal ultrasound at least 48 hours after birth antibiotic treatment can increase risk of renal • Known or suspected spinal abnormality scarring-early antibiotics in febrile child • Bowel and bladder dysfunction not improving with • Most of time, pyelonephritis is associated with fever, treatment nausea, vomiting, or flank pain

Case 2

• 11 year old male with night wetting since toilet training • No day urinary symptoms • Daily, soft bowel movements • Urine – specific gravity 1.020, otherwise negative • Refuses to do sleepovers/overnight camp • Does not want to talk about the issue, parent answers questions in clinic • Parents have tried to limit fluids, void before bed, parents wake child to urinate about 1-2 hours after bed.

11 4/10/19

Nocturnal Enuresis Nocturnal Enuresis

• Incontinence during sleep in a child five years of • Primary nocturnal enuresis – Involuntary incontinence at night by children old enough to be age or older expected to have bladder control • More common in boys – Never had bladder control for > 6 months at night • Secondary nocturnal enuresis • Self limited, 15% spontaneous cure annually – Involuntary incontinence at night by children old enough to be – ~15% in 5 yo expected to have bladder control – 10% in 7 yo – Incontinence reoccurs after at least 6 months of continence. – Comorbid behavioral/emotional disorder – 5% in 10 yo – Stressful life events can cause relapse – 2-3% in 12-14 yo • Separation or divorce of parents – 1-2 % > 15 yo • Birth of sibling – Occasional presentation for GU tract abnormality

Nocturnal Enuresis Nocturnal Enuresis Presentation

• Younger children are more likely to experience • Failure to arouse - stress importance to not lay spontaneous resolution without therapy blame on child • Children 5-7 years of age may be offered – Child described as deep sleeper nonpharmacologic treatment if they are • Increased urine volume at night motivated • Large wetted volume • If child is not bothered by enuresis consider • Normal bladder function during the day delaying treatment until motivated.

12 4/10/19

Nocturnal Enuresis Evaluation Nocturnal Enuresis Treatment

• Screen for daytime bladder and bowel • Moisture Alarm dysfunction – only treatment known to speed up possible cure • Primary vs secondary enuresis • Pharmacologic Therapy • Typically no physical abnormalities – Will not speed up cure, take until normally outgrow • Desmopressin • Urinalysis evaluating for proteinuria, glucosuria, • Oxybutynin concentrating defect, infection • Imipramine • Consider post void residual • Alternative treatment – Hypnosis • Radiological imaging is not necessary for – Acupuncture primary nocturnal enuresis – Chiropractic therapy – Consider for secondary nocturnal enuresis – Herbal therapy

Nocturnal Enuresis treatment Nocturnal Enuresis Treatment

• Desmopressin– analogue of antidiuretic hormone – Reduces urine production – 0.2 mg tablet with max dose 0.6 mg – Nasal spray no longer indicated for nocturnal enuresis • Moisture alarm – Taken ONLY right before bed – 60-80% become dry, 50% long term – Limited side effects-hyponatremia – More effective if used as recommended • Overdrinking before bed can lead to hyponatremia • Potty MD - family assistance program-30% discount – Limit fluids to 4-8 ounces starting 2 hours before bed – Provider has to sign up and provide family with code – effective in 70% of cases, younger age less effective – Can be taken just for social events, if desired

13 4/10/19

Nocturnal Enuresis Treatment Nocturnal Enuresis – Alternative Therapies

• Anticholinergic - Oxybutynin • Hypnosis, acupuncture, chiropractic therapy, and – reduce bladder contractions, increase capacity herbal therapy have weak and inconclusive – Primary side effects – dry mouth, facial flushing, constipation – studies have shown not very effective alone for night wetting effectiveness. • Combination Anticholinergic and Desmopressin • Tricyclic Antidepressant – Imipramine – Anticholinergic relaxing effect on bladder wall, stimulation of the external sphincter, central effect on enuresis which is not well understood – Comparison to desmopressin has shown similar effectiveness but significantly more side effects – Low doses, 10-25 mg

Nocturnal Enuresis

• University of Iowa currently has a moisture alarm study. – Determine if alternative activation of the alarm would be more effective in eliminating incontinence

QUESTIONS

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