This Month in Pediatric Urology

Oxybutynin for Urinary Symptoms inChildren with Williams-Beuren Syndrome

Williams-Beuren syndrome is a rare neurologicaldevelopmental disorder characterized by distinctivefacial features, an unusually cheerful demeanor,ease with strangers, developmental delay in stronglanguage skills, cardiovascular problems (eg supra-valvular aortic stenosis), transient hypercalcemiaand urinary symptoms of frequency, urgency andincontinence. Sammour et al (page 253) from SãoPaulo, Brazil prospectively studied the effects ofoxybutynin on the urinary symptoms for 12 weeks in36 children with Williams-Beuren syndrome servingas their own controls. The patients acted as theirown control, and they and their families knew theywere receiving the medication. Urological evalua-tion included symptom scores, and baseline urody-namics and sonography, which was repeated 12weeks after initiation of 0.6 mg/kg oxybutynin di-vided into 3 doses daily. At the completion of the12-week course of oxybutynin, urinary symptomsand quality of life were substantially improved. Mi-nor side effects of the oxybutynin occurred in 3 pa-tients but did not result in a need to stop the med-ication.

Limitations of the study are that a true controlgroup was not included and that the patients andparents knew they were receiving the medication incontrast to the use of a placebo. However, that thepatients acted as their own controls, and quantita-tive urodynamic and qualitative system score im-provements were noted, support the authors’ conclu-sion that oxybutynin was well tolerated and improvedthe urinary symptoms in patients with Williams-Beuren Syndrome.

Temporal Trends in theIncidence of Kidney Stones in Children

Dwyer et al (page 247) from Rochester, Minnesotaperformed a 25-year population based study to de-termine trends in the incidence of kidney stones inchildren. Using the Rochester Epidemiologic Projectas their data source, they identified 84 children di-agnosed with kidney stones under the age of 18years in Olmsted County, Minnesota from 1984 to2008. The incidence rate increased 4% each calendar

year throughout the 25-year period due to a 6% per

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© 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.

year increase in the incidence of kidney stones inchildren 12 to 17 years old. Computerized tomogra-phy identified 6% vs 76% of stones from 1984 to 1996vs 1997 to 2008. The increased diagnosis rate maybe due to more sensitive imaging technology in thelatter years. The incidence of spontaneous stone pas-sage remained the same during the entire studyperiod. The exact cause of the increased incidence ofkidney stones remains to be determined. The extentof the metabolic evaluation performed in these pa-tients varied among providers, and there was noconsistent documentation in the medical record thatstone formers were counseled about increased wa-ter intake, and decreased dietary sodium, meatand oxalate intake. These findings highlight theneed for improved education for physicians andhealth care providers taking care of children withnephrolithiasis.

Intractable Hemorrhagic Cystitis afterHematopoietic Stem Cell Transplantation

Hemorrhagic cystitis remains a morbid complication af-ter hematopoietic stem cell transplantation. Lukasewyczet al (page 242) from Minneapolis, Minnesota per-formed a retrospective analysis of 861 patients un-dergoing hematopoietic stem cell transplantationbetween 1996 and 2010. All patients received 2-mer-captoethanesulfonate (mesna) to bind the active me-tabolite of cyclophosphamide acrolein in the urine aspart of the transplant protocol. Severe hemorrhagiccystitis developed within an average of 28 days frominception of cyclophosphamide therapy in 40 pa-tients with a median age of 14.1 years. At thediscretion of the treating physician urinary diver-sion with percutaneous nephrostomy tube wasperformed in 11 children with intractable hemor-rhagic cystitis. Of these 11 patients 4 experiencedcomplete resolution of the cystitis, 4 died of unre-lated causes and 3 had a protracted course ofcystitis without complete resolution. The serious-ness of the disease is illustrated by the extrememorbidity and 55% mortality rate in this study.However, sole use of percutaneous nephrostomytube without the need for ancillary treatment op-tions such alum irrigation and formalin with as-sociated morbidity is a potential promising ther-

apy for this extremely difficult population. As

Vol. 188, 3-5, July 2012Printed in U.S.A.

DOI:10.1016/j.juro.2012.04.028

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noted by the authors, a prospective study isneeded to confirm the applicability of percutane-ous urinary diversion as first line therapy for se-vere hemorrhagic cystitis.

Histology Proven Malposition of DHAImplant Associated with Failed EndoscopicTreatment of Vesicoureteral Reflux

The advent of a safe endoscopic material, dextrano-mer/hyaluronic acid (DHA), has revolutionized sur-gical care for many patients with vesicoureteral re-flux. However, what remains a mystery is whyendoscopic treatment fails in some patients but notin others. Ben-Meir et al (page 258) from PetachTikva, Israel histologically evaluated the position ofthe DHA implant in the distal segments of 22 ure-ters in 13 children who underwent open ureteralsurgery after failed endoscopic treatment of reflux.Histological evaluation revealed that the endoscopicmaterial was “abnormally” positioned in the musclefiber in 2 and the adventitia in 14, and was peri-ureteral in 5 ureters. As the authors note, becausethere was no control group of histological analysis ofDHA implants in cases successfully treated, theycannot confirm that the position of the implantcaused the persistent reflux. To my knowledge, thisis the first report to document the location of endo-scopic material after failed endoscopic treatment.However, the question remains where does this ma-terial go after successful treatment?

Bacterial Virulence and Patternsof Urinary Tract Infection in Children

Urinary tract infections (UTIs) remain the mostcommon cause of morbidity in pediatric urologicalpatients. Although classic teaching has indicatedthat a third of patients with a febrile UTI have sometype of anatomical abnormality, the clinical signifi-cance of many of these abnormalities is now beingquestioned as two-thirds of patients have unex-plained reasons for a febrile UTI. Storm et al (page236) hypothesized that inherent bacterial viru-lence, not anatomical abnormalities, may explain,and in the future help treat febrile and nonfebrileUTIs. The hypothesis they tested is that the levelof in vitro cytokine interleukin 6 is inversely pro-portional to the virulence of Escherichia coli iso-lates from pediatric patients with UTIs of variousetiologies. The 40 E. coli isolates were from pa-tients with nonfebrile UTIs, neurogenic bladder orfebrile UTIs and vesicoureteral reflux. In vitrointerleukin 6 response was significantly lower inpatients with febrile UTIs vs those with nonfebrileUTIs. This groundbreaking work clearly shows a

need for further investigation into the bacterial

virulence of UTIs in contrast to the presentdogma, which focuses on anatomical abnormali-ties. Hopefully, this study and future investiga-tions will fuel the need for a paradigm shift in howwe approach the diagnosis and treatment of UTIs.

Factors Predicting Improvementin Renal Function after Pyeloplasty

How a kidney will perform after release of obstruc-tion remains an important clinical question. Chipdeet al (page 262) from Lucknow, India attempt topredict which factors will define improvement inrenal function after pyeloplasty. In a prospectivestudy of 52 children they examined preoperativesonographic morphometrics and urinary creati-nine-to-protein ratio obtained at pyeloplasty topredict ultimate renal function after the release ofobstruction. The outcome variable was differentialrenal function based on diuretic renography. Theultrasound parameters defined before and afterpyeloplasty were the anteroposterior (AP) pelvicdiameter, pelvic cortical thickness and pelvis/cor-tex ratio. The pelvis/cortex ratio was calculated asthe maximum anteroposterior pelvic diameter di-vided by the pelvic cortical thickness.

The patients were divided into 3 groups based ondifferential change in renal function between thepreoperative and 6-month postoperative diureticrenogram. Group 1 included patients with no orless than 5% change in differential renal function,group 2 those with improved differential renalfunction defined as an increase by 5% or more andgroup 3 consisted of patients with deterioration indifferential renal function of greater than 5%. The2 sonographic parameters of the AP pelvic diam-eter and pelvis/cortex ratio were able to predictthe outcomes of pyeloplasty. For patients with apreoperative AP pelvic diameter less than 50 mmor pelvis/cortex ratio less than 15 mm greater than5% improvement in renal function was noted ondiuretic renography. In regard to the biochemicalparameters of spot protein creatinine, the bladdersample was not predictive of pyeloplasty outcome,whereas the pelvic urine was statistically signifi-cant with a ratio of less than 0.5 predicting im-provement.

One should be cautious when interpreting thesefindings as a 5% change in differential renal func-tion in the affected kidney may not be statisticallysignificant. Furthermore, patients who had poorlyfunctioning kidneys or a differential renal func-tion at the time of surgery of less than 30% wereexcluded from this study. Further caution is war-ranted secondary to the reproducibility of the di-uretic renogram with regard to differential renal

function and the confounding variables such as

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state of hydration, timing of administration of fu-rosemide, presence or absence of a functioningbladder catheter and background calculations, allof which can lead to subtle variability in the base-line calculations of differential renal function, iesupranormal renal function. Finally, improve-ment in differential renal function of one kidney

implies a potential decline in the other kidney

which in this case is the contralateral normal kid-ney. Nevertheless, the authors are to be com-mended for documenting in prospective fashionvariables that may predict outcomes after repairof urethral pelvic junction distention.

Larry S. Baskin

Assistant Editor