Larisa Kovacevic

Enuretic children with obstructive sleep apnea syndrome: Should they see otolaryngology first?

OBJECTIVES To study: (1) the prevalence of diurnal urinary incontinence (DI) and nocturnal enuresis (NE) in children with obstructive sleep apnea syndrome (OSAS) who underwent surgery for their upper airway symptoms, (2) the postoperative rate of enuresis resolution, and (3) factors that may predict lack of improvement post surgery. PATIENTS AND METHODS An observational, pilot study of children 5-18 years of age with OSAS and NE who underwent tonsillectomy and/or adenoidectomy (T&A) between 2008 and 2010 was performed. Study consisted of a phone interview and chart review. Severity of NE and DI, frequency, arousal and sleeping disturbances were assessed pre and post T&A. Factors associated with failure to respond were analyzed using a logistic regression model. RESULTS Among the 417 children who underwent T&A, 101 (24%) had NE (61 males, mean age 7.8 ± 2.5 years), and of these 24 had associated DI (6%). Mean postoperative follow-up was 11.7 months. Of the 49 whose NE responded to T&A (49%), 30 resolved within 1 month postoperatively. DI resolved in 4 children (17%). There was a statistically significant difference between responders and non-responders regarding the presence of prematurity, obesity, family history of NE, type of enuresis, enuresis severity, and ability to be easily aroused. CONCLUSION NE was present in about one fourth of children with OSAS undergoing surgery, and resolved in about half. Lower response rate was associated with prematurity, obesity, family history of NE, presence of non-monosymptomatic NE, severe NE preoperatively, and arousal difficulties.

From Hypercalciuria to Hypocitraturia—A Shifting Trend in Pediatric Urolithiasis?

PURPOSE We analyzed the metabolic abnormalities in children with urolithiasis, and the relationship between diet and hypocitraturia. MATERIALS AND METHODS A single center, retrospective analysis was conducted in all children with renal and/or ureteral calculi seen at our Multidisciplinary Stone Clinic between January 2010 and July 2011. Data at presentation were extracted from the clinical database. RESULTS We analyzed 63 children (37 girls) with urolithiasis with a mean age of 13.43 ± 4.61 years. Of the 45 patients with 24-hour urinalysis, a metabolic risk factor was present in 68.9%, with hypocitraturia (58.1%) and hypercalciuria (48.3%) being the most common. Children with isolated hypocitraturia had lower urinary magnesium and potassium levels (1.06 ± 0.62 mg/kg and 0.53 ± 0.24 mmol/kg per day) than those with no metabolic abnormalities (1.72 ± 0.61 mg/kg and 0.68 ± 0.20 mmol/kg per day) (p = 0.015 and p = 0.132, respectively). Urinary citrate was positively correlated with urinary potassium (r = 0.50, p = 0.002) and urinary magnesium (r = 0.49, p = 0.001). Dietary analysis revealed a lower intake of magnesium and potassium in children with hypocitraturia (28.97% ± 12.25% and 15.42% ± 7.25% recommended dietary index) than in normocitraturic cases (51.06% ± 17.51% and 45.23% ± 29.49% recommended dietary index) (p = 0.042 and p = 0.056, respectively). CONCLUSIONS The majority of children had an identifiable metabolic risk factor for urolithiasis, with hypocitraturia being the most common. This shift in metabolic trend may be a significant contributor to the increasing incidence in pediatric urolithiasis. Hypocitraturia appears to be dietary in origin, correlated with a low consumption of potassium and magnesium.

Why does Adenotonsillectomy Not Correct Enuresis in All Children with Sleep Disordered Breathing

PURPOSE We analyzed the outcome of nocturnal enuresis after adenotonsillectomy in children with sleep disordered breathing. We also evaluated differences in demographic, clinical, laboratory and polysomnography parameters between responders and nonresponders after adenotonsillectomy. MATERIALS AND METHODS We prospectively evaluated children 5 to 18 years old diagnosed with sleep disordered breathing (snoring or obstructive sleep apnea syndrome) on polysomnography and monosymptomatic primary nocturnal enuresis requiring adenotonsillectomy to release upper airway obstruction. Plasma antidiuretic hormone and brain natriuretic peptide were measured preoperatively and 1 month postoperatively. RESULTS Sleep studies were done in 46 children and 32 also underwent blood testing preoperatively and postoperatively. Mean ± SD patient age was 8.79 ± 2.41 years and the mean number of wet nights weekly was 6.39 ± 1.26. Polysomnography revealed obstructive sleep apnea syndrome in 71.7% of patients and snoring in 28.3%. After adenotonsillectomy 43.5% of patients became dry. Preoperative polysomnography findings indicated that responders, who were dry, had significantly more arousals and obstructive apnea episodes but fewer awakenings than nonresponders, who were wet. Significant increases in plasma antidiuretic hormone and significant decreases in plasma brain natriuretic peptide were seen in all children with no difference between responders and nonresponders. No difference between the groups was noted in age, gender, race, body mass index, constipation, preoperative number of wet nights weekly or type of sleep disordered breathing. CONCLUSIONS Nocturnal enuresis resolved after adenotonsillectomy in almost half of the children with sleep disordered breathing. Those who became dry had more frequent arousal episodes caused by apnea events than those who remained wet.

Urine proteomic analysis in cystinuric children with renal stones

INTRODUCTION The gene mutations responsible for cystinuria do not fully explain kidney stone activity, suggesting that specific proteins may serve as promoters of cystine precipitation, aggregation or epithelial adherence. In this study we assessed (1) the differences in the urinary proteins between children with cystinuria and kidney stones (CYS) and healthy controls (HC), with particular attention to the fibrosis-related proteins, and (2) the presence of diagnostic biomarkers for CYS. MATERIAL AND METHODS We conducted a pilot study comparing individual urinary proteomes of 2 newly diagnosed children with CYS and 2 age- and gender-matched HC, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Proteins of interest in both CYS and HC were selected using the following criteria: i) ≥5 spectral counts; ii) ≥2-fold difference in spectral counts; and iii) ≤0.05 p-value for the Fishers Exact Test. DISCUSSION This study demonstrates a different urinary polypeptide profile in two children with CYS compared to two HC. Of the 623 proteins identified by proteomic analysis, 180 exhibited at least a 2-fold increased relative abundance in CYS compared to HC. Of these, 39 were involved in response to stress, 26 in response to wounding, 21 in inflammatory response, 18 in immune response, and 4 in cellular response to oxidative stress. 133 proteins were found only in children with CYS, 33 of which met the selection criteria. Of these 33 unique proteins, six are known to be associated with fibrosis pathways (Table). The major limitation of this study is the small number of samples that were analyzed. Validation using highly specific methods such as ELISA is needed. CONCLUSION We provide proteomic evidence of oxidative injury, inflammation, wound healing and fibrosis in two children with CYS. We speculate that oxidative stress and inflammation may cause remodeling via actin and vimentin pathways, leading to fibrosis. Additionally, we identified ITIH and MMP-9 as potential diagnostic biomarkers and novel therapeutic targets in CYS. These proteins merit further investigation.

Adenotonsillectomy Normalizes Hormones and Urinary Electrolytes in Children With Nocturnal Enuresis and Sleep-Disordered Breathing.

OBJECTIVE To assess (1) plasma levels of antidiuretic hormone (ADH) and brain natriuretic peptide (BNP) and urinary levels of electrolytes in children with sleep disordered breathing (SDB), with or without nocturnal enuresis (NE), and (2) the effect of adenotonsillectomy (T&A) on urinary electrolytes and the secretion of ADH and BNP in children with NE and SDB. We previously reported post-T&A improvements in plasma levels of BNP and ADH in children with SDB and NE. However, the differences in plasma concentration of these hormones in SDB children with and without NE, and their relationships with urinary electrolytes, have not yet been addressed. METHODS This prospective study compared concentrations of urinary electrolytes and plasma ADH and BNP in (1) children with SDB and NE (study group) and an age- and sex-matched control group of children with SDB without NE, and (2) the study group before and 1-month after T&A. RESULTS Compared with the control group (n = 31), the study group (n = 37) exhibited significantly lower ADH (P = .04) and higher BNP (P = .009) plasma levels. The differences in urinary electrolytes were not significant. Post-T&A, the study group showed significantly decreased BNP (P = .018), urinary sodium-to-creatinine ratio (P = .02), and urinary calcium-to-creatinine ratio (P = .007) compared with the pre-T&A values. Post-T&A changes in urinary calcium were significantly correlated with changes in sodium excretion (P = .002) and in plasma levels of BNP (P <.001). CONCLUSION The presence of NE is associated with altered ADH and BNP levels in children with SDB. T&A led to normalization of ADH and BNP, probably through a calcium- and sodium-dependent mechanism.

Do Overweight and Obese Pediatric Stone Formers Have Differences in Metabolic Abnormalities Compared With Normal-weight Stone Formers?

OBJECTIVE To determine if 24-hour urinary parameters in children with nephrolithiasis across 4 institutions were influenced by body mass index (BMI). MATERIALS AND METHODS The 24-hour urinary parameters obtained from children with nephrolithiasis between 2000 and 2013 were stratified by BMI percentile ≥85th and <85th (overweight and obese patients vs healthy weight, respectively). A total of 206 children were included in the study. Exclusion criteria included patients with a history of spina bifida, neurogenic bladder, and cerebral palsy, and patients on medical treatment before the first 24-hour urine collection. RESULTS Overweight and obese patients consisted of 35.4% of the cohort (n = 73). Metabolic abnormalities were present in 130 children (63.1%). The most common abnormality present in the <85th percentile was hypercalciuria (32.3%), and in the ≥85th percentile, hyperoxaluria (37.0%). Univariable and multivariable analyses revealed that overweight and obese children were more likely to have low urinary volume and elevated uric acid compared to normal-weight children. CONCLUSION Although there is a link between stone formation and BMI in adults, no definitive conclusions have been proven in the pediatric literature. Our study indicates that stone-forming children who are overweight or obese have low urinary volume and elevated uric acid compared to normal-weight stone-forming children.

Lower Health Related Quality of Life and Psychosocial Difficulties in Children with Monosymptomatic Nocturnal Enuresis—Is Snoring a Marker of Severity?

PURPOSE Sleep disordered breathing in children is linked to numerous negative psychosocial consequences, including lower health related quality of life, increased behavioral problems and impaired neuropsychological functioning. We examined whether snoring, which is the least severe form of sleep disordered breathing, or health related quality of life could account for the increased rate of psychosocial difficulty in children with monosymptomatic nocturnal enuresis. MATERIALS AND METHODS Patients diagnosed with monosymptomatic nocturnal enuresis seen at an outpatient pediatric urology clinic completed measures of health related quality of life (Obstructive Sleep Apnea Syndrome-18-Item Questionnaire), sleep disordered breathing (Pediatric Sleep Questionnaire) and psychosocial difficulty (Pediatric Symptom Checklist). Patients were categorized into 2 groups (snoring vs no snoring) based on the Pediatric Symptom Checklist snoring subscale score. RESULTS Included in the study were 62 males and 45 females with a mean ± SD age of 9.09 ± 2.58 years and a mean body mass index of 21.00 ± 6.93 kg/m(2) (range 13 to 49). The sample was evenly split between 56 snorers (52.3%) and 51 nonsnorers (47.7%). Compared to children with monosymptomatic nocturnal enuresis who did not snore, MANCOVA results revealed that patients with monosymptomatic nocturnal enuresis who snored had significantly more externalizing problems and total psychosocial problems, in addition to significantly more impairment in all areas of health related quality of life. CONCLUSIONS Snoring in children with monosymptomatic nocturnal enuresis puts them at increased risk for behavioral and psychosocial problems, in addition to impaired health related quality of life. These findings support the need for future studies of the neurological links between sleep disordered breathing and monosymptomatic nocturnal enuresis.

National multi-institutional cooperative on urolithiasis in children: Age is a significant predictor of urine abnormalities

INTRODUCTION Pediatric nephrolithiasis is a growing problem and prior studies have shown the greatest increase in nephrolithiasis in the adolescent population. Metabolic abnormalities have historically been cited as the primary cause of pediatric nephrolithiasis; however, dietary and other factors such as obesity have also been studied with mixed results. OBJECTIVE We reviewed the charts of pediatric patients with a history of nephrolithiasis to determine the number and types of metabolic abnormalities present on 24-h urine analysis. STUDY DESIGN We retrospectively reviewed the charts of all pediatric patients with a history of nephrolithiasis from 1999-2013 across four different institutions. The subjects were excluded if they had a history of spina bifida, neurogenic bladder, cerebral palsy, isolated bladder stones, or if they were on medical therapy for nephrolithiasis before the first 24-h urine collection. RESULTS There were 206 subjects included in the analysis with an average age of 13 (±3.9) years. The patients were stratified into two age groups based on an apparent bimodal distribution of metabolic abnormalities, ≤10 years and >10 years of age. Metabolic abnormalities were present in 130 children (63.1%) and there was a difference between the groups, with children ≤10 years more likely to have a metabolic abnormality compared with those >10 years of age (75% vs. 60.6%, p = 0.0443) on univariate analysis. In children ≤10 years hypercalciuria was the most common disorder present (48.4%), and in children >10 years hypocitraturia was the most common disorder present (26.1%). Children ≤10 years of age were more likely to have normal volume (p = 0.006), elevated urinary oxalate (p = 0.0351), elevated urinary calcium (p < 0.001), elevated supersaturation of calcium phosphate (p < 0.001), and elevated supersaturation of calcium oxalate (p = 0.002). On multivariate analysis, children ≤10 years of age were more likely to have normal volume, hyperoxaluria, elevated supersaturation of calcium phosphate and a trend towards hypercalciuria (Table). DISCUSSION Our study reveals that younger children are more likely to have a metabolic abnormality present on 24-h urine analysis. This has important implications when deciding on treatment options, with younger children potentially requiring more aggressive management with medical therapy. Older children were more likely to have low urinary volume and their most common metabolic abnormality was hypocitraturia. Although dietary factors have not been established as the definitive reason behind the rising incidence of nephrolithiasis in the adolescent population, older children may benefit more from diet modification with a strong focus on increasing volume intake. CONCLUSION We found differences in younger compared with older age groups in terms of the number and types of metabolic disorders present. Children ≤10 years of age were more likely to have a metabolic disorder including elevations in calcium, oxalate and supersaturation of calcium phosphate, while children >10 years of age were more likely to have low urinary volume. These differences have important implications for future investigative studies on the rising incidence as well as the best course of treatment for children with nephrolithiasis.

Adenotonsillectomy improves quality of life in children with sleep-disordered breathing regardless of nocturnal enuresis outcome

BACKGROUND Nocturnal enuresis (NE) and sleep-disordered breathing (SDB) have both been associated with impaired health-related quality of life (HRQoL). The following were investigated: (1) whether tonsillectomy and/or adenoidectomy (T&A) significantly affect the HRQoL in children with NE and SDB, and 2) differences in HRQoL between children with NE persistence versus resolution post-T&A. METHODS This was a prospective study comparing the HRQoL of children with SDB and NE (study group) pre- and 4 weeks post-T&A, and the HRQoL of children with SDB without NE (control group) (independent t-tests). HRQol was assessed using the Obstructive Sleep Apnea Quality of Life 18 questionnaire (OSAS-18), a validated measure containing five subscales that combine to create a total score. Individual items were scored on a Likert-type scale ranging from 1 (none of the time) to 7 (all of the time). Symptoms of SDB were evaluated using the validated Pediatric Sleep Questionnaire (PSQ). Mixed ANOVA was conducted to evaluate changes in the measures between the wet and dry children post-T&A. Pre- and post-T&A change scores were calculated for both the PSQ and the OSAS-18. RESULTS There were 30 children in the study group (18 male, mean age 9.07 years, SD 2.19), and 30 age-matched controls (16 male). There were no statistically significant differences between the two groups in regards to OSAS-18 total, PSQ total, BMI, diagnosis of snoring or OSAS on sleep study, or race. Overall, OSAS-18 and PSQ scores significantly improved in all children post-surgery (p < 0.001; p < 0.001, respectively), with no significant differences between dry and wet children post-T&A. The correlation between the pre- and post-T&A change scores on the OSAS-18 and PSQ was significant (r(29) = 0.58, p = 0.001), suggesting that a reduction in SDB symptoms post T&A is related to improved HRQoL. CONCLUSIONS T&A significantly improved HRQoL in all children with SDB and NE, regardless of NE outcomes. These findings support recommendations for T&A in children with SDB with or without NE.

Factor Analysis of the Pediatric Symptom Checklist in a Population of Children with Voiding Dysfunction and/or Nocturnal Enuresis

The research objective was to identify the factor structure of the pediatric symptom checklist (PSC) in children with voiding dysfunction and/or nocturnal enuresis who were seen in a pediatric urology clinic. Retrospective chart reviews were conducted for 498 consecutive patients, ages 6–16, who were seen over a 13-month period. The PSC, a 35-item measure used to screen for psychosocial difficulties, was completed by the patient’s caregiver. Confirmatory factor analyses using three previous models were conducted. A four factor model comprised of internalizing, externalizing, attention problems, and chronic illness factors represented the best fit to the data. Within this population, the PSC appears to capture internalizing and externalizing problems, difficulties with attention, and possible side effects of a medical condition. This information could aid clinicians in assessing adjustment difficulties within this population and concurrently allow researchers to examine whether these specific factors are related to other relevant outcomes.