This Month in Pediatric Urology

Article Outline

• Endourological Management of Pediatric Stone Disease
• Post-Pyelonephritic Renal Scarring
• Evidence of Partial Anti-Enuretic Response Related to Poor Pharmodynamic Effects of Desmopressin Nasal Spray
• Hypospadias and Intake of Nutrients Related to One-Carbon Metabolism
• Copyright

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Endourological Management of Pediatric Stone Disease 

The miniaturization of endourological instrumentation has led to a significant increase in the application of these interventional techniques in children during the last decade. Smaldone et al (page 17) from Pittsburgh, Pennsylvania present a comprehensive literature review of the indications, techniques, complications and efficacy of endourological management of urinary stones in children. Shock wave lithotripsy (SWL) in children has resulted in stone-free rates similar to those of adults and has evolved as the preferred treatment modality for uncomplicated renal and proximal calculi 15 mm or smaller at many centers. Complications have been few but stone-free rates after single session SWL remain as low as 44%, often requiring multiple sessions. Percutaneous nephrolithotomy using smaller nephroscopes and more efficient energy sources for intracorporeal lithotripsy has replaced open surgery for large stone burdens in children of all ages, achieving high overall efficacy rates approaching 90%, although many have required multiple tracts and/or staged procedures, with transfusion rates as high as 14% to 24% in some series. In an effort to reduce morbidity sandwich therapy with intitial percutaneous nephrolithotomy followed by SWL has been used for residual stone fragments, achieving cumulative stone-free rates greater than 90%.

Associated with the miniaturization and improvement of pediatric endoscopic equipment, and combined with use of the holmium laser, ureteroscopy has evolved as the treatment of choice for children with distal ureteral stones. Higher success rates than SWL have been achieved after 1 treatment. The success with distal calculi has led to expansion of the use of ureteroscopy to the treatment of upper tract calculi with stone-free rates as high as 88% to 100% and complication rates similar to those in adults. Renal pelvic stones are being treated using ureteral access sheaths and miniature flexible ureteroscopes. The authors acknowledge considerable variation among institutions regarding the choice of initial treatment for urinary stones in children, the definition of stone-free status, and the optimal posttreatment and long-term surveillance imaging. Prospective comparative trials are needed before consensus can be achieved regarding the most effective primary treatment modality.

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Post-Pyelonephritic Renal Scarring 

Many factors have been shown to influence the risk of renal scarring following acute pyelonephritis, including patient age, bacterial virulence properties, treatment delay and vesicoureteral reflux (VUR) grade, if present. To assess the influence of VUR and possible geographic variations which might then suggest genetic and/or socioeconomic influences, Faust et al (page 290) from Washington, D. C. conducted an extensive meta-analysis of all peer reviewed articles between 1980 and 2006. Inclusion criteria were dimercapto-succinic acid (DMSA) scan proven acute pyelonephritis associated with fever and positive urine culture, followup DMSA scan at least 3 months after the acute illness to assess for scar formation and no recurrent urinary tract infection before the followup scan. Major characteristic data were obtained including geographic location, average patient age, gender distribution, presence and grade of VUR, and percent of patients with renal cortical abnormalities on followup DMSA scans.

Of 187 citations 23 patient cohort studies (greater than 2,000 children) were available for analysis, including 17 (74%) prospective studies, 5 (22%) from Asia, 11 (48%) from Europe, 2 from Latin America, 2 from the Middle East, 1 from the United States, 1 from Oceania and 1 multicenter, multi-regional study. The initial baseline DMSA scan was performed within 15 days of symptoms in 19 cohorts, while the followup scan was done at a median of 6 months after the baseline DMSA scan. The overall incidence of renal scarring in terms of patients and renal units was 41.6% and 37%, respectively. Patients with VUR demonstrated an increased likelihood of having a scar after acute pyelonephritis than those without VUR (odds ratio 2.8; 95% CI 1.9, 4.2). The rate of post-pyelonephritic scarring was different across some geographic regions, ranging from 26.5% in Australia to 49% in Asia. The authors conclude that the presence of VUR conferred a significant risk of approximately 3-fold for the development of renal cortical scarring following DMSA scan documented acute pyelonephritis.

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Evidence of Partial Anti-Enuretic Response Related to Poor Pharmodynamic Effects of Desmopressin Nasal Spray 

Desmopressin achieves nocturnal dryness in only 10% to 50% (average 20%) of children with nocturnal enuresis. Approximately a third of patients will have a partial response usually defined as a greater than 50% reduction in wet nights. Factors predictive of response include nocturnal polyuria and normal bladder capacity, with the best response seen in those who experience a reduction in nocturnal urine volume. In contrast, persistent nocturnal polyuria during treatment suggests an insufficient anti-diuretic effect. De Guchtenaere et al (page 302) from Belgium evaluated prospectively the pharmacodynamic factors involved in partial desmopressin response or desmopressin resistance in 64 children with monosymptomatic nocturnal enuresis and proven nocturnal polyuria (nocturnal diuresis greater than 130% of estimated bladder volume). The study consisted of 9 timed urine collections starting in the evening 1 hour before administration of 20 mcg desmopressin nasal spray and continuing for 16 hours. These collections were done on 2 separate home based test days during fluid restriction (1) and during an oral fluid load (1). Urinary volume, urine osmolality and diuresis rate were measured throughout the timed collections.

Under fluid restriction 16 of the 64 children failed to achieve urine concentration greater than 850 mOsmol/l in the midnight collection when the highest bioactivity of desmopressin is expected. After a fluid load a third of the patients failed to achieve urinary osmolality greater than 700 mOsmol/l and diuresis rate was 0.5ml per minute. There was also an increase in time to reach maximal urine concentration and a decrease in maximal urine concentration during the night. The authors conclude that insufficient pharmacodynamic effect of desmopressin may be related to an inappropriate renal response or to nocturnal over hydration. Those children with an insufficient and short duration of action might benefit from an increased dose of desmopessin. In addition to pre-bedtime fluid restriction, they recommend that desmopressin be administered at least 1 hour before bedtime and up to 2 hours before bedtime in cases of therapy resistance to reduce the diuresis rate during the early night.

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Hypospadias and Intake of Nutrients Related to One-Carbon Metabolism 

In addition to folic acid, several nutrients that contribute to one-carbon metabolism (folate, choline, vitamins B12 and B6, thiamine, riboflavin, methionine and zinc) may be associated with a reduced incidence of birth defects. Current knowledge regarding the association of nutrient intake and hypospadias is limited. Using a large database from the National Birth Defects Prevention Study, Carmichael et al (page 315) from Oakland, California and Atlanta, Georgia assessed dietary intake by distributing a food frequency questionnaire to 915 mothers of boys born with penile shaft or more proximal hypospadias and compared to 2,266 mothers of normal controls. Intake of folic acid containing supplements was not associated with hypospadias after adjustment for several potential confounders. However, in those women who took dietary supplements during pregnancy an increased intake of choline, methionine and vitamin B12 were associated with a decreased risk of hypospadias. Of women who did not take supplements an increased risk of hypospadias was seen in those with a higher vitamin B12 intake. The authors conclude that intake of certain nutrients involved in one-carbon metabolism may be associated with a reduced risk of hypospadias but more epidemiological or experimental study is needed to better understand and explain these observations.