Diurnal rhythm of urinary aquaporin-2 in children with primary monosymptomatic nocturnal enuresis.

Background/aim: Nocturnal enuresis can be frustrating for children and their families as the child ages. Our aim is to evaluate urine aquaporin 2 (AQP-2) as a noninvasive biomarker of water balance in children with primary monosymptomatic nocturnal enuresis (PMNE). Material and methods: The study included 90 children; sixty-eight children suffering from PMNE aged (9.57 ± 2.16) years and 22 healthy children with good toilet control, matched sex and age. All enuretic children were subjected to complete history taking, clinical evaluation, and bed wetting diary. Serum arginine vasopressin (AVP) and urine AQP-2 were tested in the morning (at 9-11 am) and evening (at 9-11 pm). Blood urea, creatinine, Na, glucose, urine osmolality, Ca/Cr, Alb/Cr and specific gravity were tested simultaneously. Results: Serum AVP, urine AQP-2, and urine osmolality were statistically lower in patients than controls. Patients had a significantly lower level of night serum AVP concentrations, urine AQP-2, and urine osmolality than the corresponding morning level. Urine AQP-2 was significantly correlated with urine osmolality (p < 0.05). AQP-2 had a sensitivity of 90% and a specificity of 70%. However, no statistically significant correlation was found between serum AVP and urine AQP-2. Conclusion: Primary monosymptomatic nocturnal enuresis in children could be associated with reduction of urine excretion of AQP-2 at night. Urine AQP-2 is significantly correlated with urine osmolality. Therefore, it may be a noninvasive biomarker of hydration status in children with PMNE, with good sensitivity and specificity.

The Role of Hyposthenuria in Enuresis Among Paediatric Patients With Sickle Cell Disease.

Objectives: Enuresis is common among children with sickle cell disease (SCD). Many risk factors have been postulated, but its relation to hyposthenuria is debatable. This study aimed to determine the prevalence of enuresis in children with SCD in Basrah, Iraq, and to examine its relation with hyposthenuria. Methods: A cross-sectional epidemiological study was performed on children with SCD who met the inclusion criteria at the Basrah Center for Hereditary Blood Diseases from December 2020 to May 2021. A questionnaire was used to collect relevant data. Blood samples were tested for haemoglobin genotype, certain blood indices and serum haemoglobin. Urine was tested for albumin and creatinine, and the specific gravity was measured using urine dipsticks. The relationships between enuresis and various sociodemographic and clinical variables were assessed. Binary logistic regression analysis was done to examine the independent risk factors of enuresis. Results: A total of 161 out of 200 eligible children were included in this study (response rate: 80.5%). The majority of participants (60.9%) were males. The mean age of the participants was 10.9 ± 2.9 years. Enuresis was reported in 50 (31.1%) patients. The independent risk factors for enuresis included family history of enuresis (adjusted odds ratio [OR] = 5.94, 95% confidence interval [CI]: 2.54-13.89; P <0.001), hyposthenuria (OR = 3.76, 95% CI: 1.25-11.30; P = 0.018) and sleep disorders (OR = 2.90, 95% CI: 1.19-7.06; P = 0.019. Conclusion: Enuresis is common among children with SCD in Basrah, Iraq. Hyposthenuria was significantly associated with enuresis. Family history of enuresis and sleep disorders were also found to be significantly related to enuresis.

Urine metabolic phenotyping in children with nocturnal enuresis and comorbid neurobehavioral disorders.

Nocturnal enuresis (NE) is a common problem among 10% school-aged children. The etiologies underlying childhood NE is complex and not fully understood nowadays. Nevertheless, increasing evidence suggests a potential link between neurobehavioral disorders and enuresis in children. In this study, we aimed to explore novel metabolomic insights into the pathophysiology of NE and also, its association with pediatric psychiatric problems. Urine collected from 41 bedwetting children and 27 healthy control children was analyzed by using 1H-nuclear magnetic resonance spectroscopy from August 2017 to December 2018. At regular follow-up, there were 14 children with refractory NE having a diagnosis of attention deficient hyperactivity disorder (ADHD) or anxiety. Eventually, we identified eight significantly differential urinary metabolites and particularly increased urinary excretion of betaine, creatine and guanidinoacetate linked to glycine, serine and threonine metabolism were associated with a comorbidity of neurobehavioral disorders in refractory bedwetting children. Notably, based on physiological functions of betaine acting as a renal osmolyte and methyl group donor, we speculated its potential role in modulation of renal and/or central circadian clock systems, becoming a useful urinary metabolic marker in diagnosis of treatment-resistant NE in children affected by these two disorders.

Desmopressin response in nocturnal enuresis showing concentrated urine.

BACKGROUND: In Japan, the use of desmopressin (1-desamino-8-D-arginine vasopressin) is only recommended for nocturnal enuresis with unconcentrated first morning urine, which suggests a relative deficiency of antidiuretic hormone secretion during sleep. However, no such limitations have been described in a standardization document of the International Children's Continence Society. We aimed to determine whether desmopressin treatment induces any response in nocturnal enuresis with concentrated first morning urine. METHODS: Outpatients aged 6-15 years who exhibited monosymptomatic nocturnal enuresis were examined. Data were obtained from 41 treatment-naive patients (median age 9.7 years) with nocturnal enuresis, who received desmopressin as their first line of treatment. The patients were divided into two groups demonstrating unconcentrated (osmolality < 800 mOsm/L, Low-Osm group) and concentrated (osmolality ≥ 800 mOsm/L, High-Osm group) first morning urine, respectively; we compared the response to desmopressin treatment between the groups at 1 month after the administration or updosing of desmopressin; responses were defined as partial or complete according to the International Children's Continence Society standards. Mann-Whitney U-tests or Fisher's exact tests were used for analysis. RESULTS: The Low-Osm (median age 9.6 years) and High-Osm groups (median age 9.7 years) had 14 and 27 patients, respectively; the response rates to desmopressin treatment were 64.3% and 59.2%, respectively, indicating no significant differences (P = 0.99). CONCLUSION: Desmopressin treatment may be a feasible option for treating nocturnal enuresis with concentrated first morning urine.

High daily salt intake had a negative impact on how well nocturnal enuresis treatment worked on children aged 7-10 years.

AIM: We investigated whether the daily salt intake of children with nocturnal enuresis influenced their response to 1-desamino-8-D-arginine vasopressin therapy. METHODS: This study comprised 129 children (67.4% boys) with a median age of 9.2 years (range 7.2-10.4) with monosymptomatic nocturnal enuresis who were seen at Kansai Medical University Hospital, Osaka, Japan, from 2013 to 2017. Urinary sodium concentrations were determined using a spot urine test, and the children were divided into appropriate (n = 55) and excessive salt intake (n = 74) groups based on Japanese Government guidelines. After a month of therapy, the treatment responses were compared for 39 and 50 children, respectively. RESULTS: There were no significant differences in the urea nitrogen-to-creatinine or calcium-to-creatinine ratios in the two groups. However, the excessive salt intake group showed a significantly reduced treatment response to the appropriate salt intake group. In addition, the excessive and appropriate salt intake groups showed median efficacy ratios of 8.2% and 21.8%, respectively, based on intention-to-treat analysis (P = 0.029) and 12.0% and 30.8% based on per-protocol analysis (P = 0.029). CONCLUSION: High daily salt intake significantly reduced the efficacy of ddavp therapy for nocturnal enuresis and consumption should be controlled during treatment.

Serum and urinary levels of brain-derived neurotrophic factor (BDNF) in enuresis. / Niveles séricos de factor neurotrófico derivado de cerebro en la enuresis.

OBJECTIVES: Enuresis is one of the most frequently seen psycho-social problems in childhood, which causes anxiety and stress in the child, thus affecting his/her self-respect and quality of life. The aim of the study was to determine the role of bladder function or psychologic factors or both as factors causing enuresis. METHODS: This study on pediatric patients with primary enuresis included 30 patients with monosymptomatic nocturnal enuresis (MonoNE), 30 patients with polysymptomatic nocturnal enuresis (PolyNE), and 30 healthy controls, making a total of 90 subjects with an age range of 8-18. In all subjects, the levels of serum and urinary Brain-Derived Neurotrophic Factor (BDNF) were measured, in addition to urinary creatinine levels and calculated as BDNF/Cr ng/mg creatinine (BDNF/ Cr). RESULTS: The serum BDNF results of the PolyNE group (0.949±0.587) were significantly lower than those of the control group (1.158±0.587) (p=0.014). The urinary BDNF results of the PolyNE group (1.107±0.360) were significantly higher than those of both the MonoNE (0.657±0.272) and the control (0.670±0.271) groups (p<0.0001). The BDNF/Cr results of the PolyNE group (1.472±0.714) were significantly higher than those of the MonoNE group (0.956±1.017) and the control group (0.931±0.618) (p=0.044 and p=0.032, respectively). CONCLUSIONS: In addition to bladder-specific problems, it is possible for anxiety and psychological stress-induced problems to occur in PolyNE. Therefore, in addition to the increasing number of studies on the bladder in enuresis, further studies on the neurogenic and psychogenic aspects of enuresis should be carried out.

OBJETIVOS: La enuresis es uno de los problemas psicosociales más frecuentes en la infancia, que causa ansiedad y estrés a los niños, afectando a su autoestima y calidad de vida. El objetivo de este estudio es la determinación del papel de la función vesical, los factores psicológicos o ambos como factores causales de la enuresis.MÉTODOS: Este estudio en pacientes pediátricos con enuresis incluyó 30 pacientes con enuresis nocturna monosintomática (ENmono), 30 pacientes con enuresis nocturna polisintomática (ENpoli) y 30 controles sanos, sumando un total de 90 individuos con un rango de edad entre 8-18 años. En todos los casos se midieron los niveles séricos y urinarios de factor neurotrófico derivado del cerebro (FNDC), además de los niveles de creatinina urinaria y se hizo el cálculo de FNDC/Cr ng/mg creatinina. RESULTADOS: Los resultados de FNDC sérico en el grupo ENpoli (0,949±0,587) fueron significativamente menores que los del grupo control (1,158±0,587) (p=0,014). Los resultados de FNDC urinario en el grupo de ENpoli (1,107±0,360) fueron significativamente mayores que los de los grupos ENmono (0,657±0,272) y control (0,670±0,271) (p<0,0001). Los resultados de FNDC/Cr el grupo ENpoli (1,472±0,714) eran significativamente mayores que los de los grupos ENMono (0,956±1,017) y control (0,931±0,618) (p=0,044 y p=0,032, respectivamente). CONCLUSIONES: Además de problemas específicos vesicales, es posible que los problemas de ansiedad e inducidos por estrés psicológico ocurran en la ENPoli. Por lo tanto, además del creciente número de estudios sobre la vejiga en enuresis, es necesario desarrollar más estudios sobre los aspectos neurogénicos y psicogénicos de la enuresis.

Serum and urinary levels of brain-derived neurotrophic factor (bdnf) in enuresis / Niveles séricos de factor neurotrófico derivado de cerebro en la enuresis

OBJECTIVES: Enuresis is one of the most frequently seen psycho-social problems in childhood, which causes anxiety and stress in the child, thus affecting his/her self-respect and quality of life. The aim of the study was to determine the role of bladder function or psychologic factors or both as factors causing enuresis. METHODS: This study on pediatric patients with primary enuresis included 30 patients with monosymptomatic nocturnal enuresis (MonoNE), 30 patients with polysymptomatic nocturnal enuresis (PolyNE), and 30 healthy controls, making a total of 90 subjects with an age range of 8-18. In all subjects, the levels of serum and urinary Brain-Derived Neurotrophic Factor (BDNF) were measured, in addition to urinary creatinine levels and calculated as BDNF/Cr ng/mg creatinine (BDNF/ Cr). RESULTS: The serum BDNF results of the PolyNE group (0.949 ± 0.587) were significantly lower than those of the control group (1.158 ± 0.587) (p = 0.014). The urinary BDNF results of the PolyNE group (1.107 ± 0.360) were significantly higher than those of both the MonoNE (0.657 ± 0.272) and the control (0.670 ± 0.271) groups (p < 0.0001). The BDNF/Cr results of the PolyNE group (1.472 ± 0.714) were significantly higher than those of the MonoNE group (0.956 ± 1.017) and the control group (0.931 ± 0.618) (p = 0.044 and p = 0.032, respectively). CONCLUSIONS: In addition to bladder-specific problems, it is possible for anxiety and psychological stress-induced problems to occur in PolyNE. Therefore, in addition to the increasing number of studies on the bladder in enuresis, further studies on the neurogenic and psychogenic aspects of enuresis should be carried out

OBJETIVOS: La enuresis es uno de los problemas psicosociales más frecuentes en la infancia, que causa ansiedad y estrés a los niños, afectando a su autoestima y calidad de vida. El objetivo de este estudio es la determinación del papel de la función vesical, los factores psicológicos o ambos como factores causales de la enuresis. MÉTODOS: Este estudio en pacientes pediátricos con enuresis incluyó 30 pacientes con enuresis nocturna monosintomática (ENmono), 30 pacientes con enuresis nocturna polisintomática (ENpoli) y 30 controles sanos, sumando un total de 90 individuos con un rango de edad entre 8-18 años. En todos los casos se midieron los niveles séricos y urinarios de factor neurotrófico derivado del cerebro (FNDC), además de los niveles de creatinina urinaria y se hizo el cálculo de FNDC/Cr ng/mg creatinina. RESULTADOS: Los resultados de FNDC sérico en el grupo ENpoli (0,949 ± 0,587) fueron significativamente menores que los del grupo control (1,158 ± 0,587) (p = 0,014). Los resultados de FNDC urinario en el grupo de ENpoli (1,107 ± 0,360) fueron significativamente mayores que los de los grupos ENmono (0,657 ± 0,272) y control (0,670 ± 0,271) (p < 0,0001). Los resultados de FNDC/Cr el grupo ENpoli (1,472 ± 0,714) eran significativamente mayores que los de los grupos ENMono (0,956 ± 1,017) y control (0,931 ± 0,618) (p = 0,044 y p = 0,032, respectivamente). CONCLUSIONES: Además de problemas específicos vesicales, es posible que los problemas de ansiedad e inducidos por estrés psicológico ocurran en la ENPoli. Por lo tanto, además del creciente número de estudios sobre la vejiga en enuresis, es necesario desarrollar más estudios sobre los aspectos neurogénicos y psicogénicos de la enuresis

Urinary nerve growth factor can predict therapeutic efficacy in children with monosymptomatic nocturnal enuresis.

AIM: To determine the urinary levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in children with monosymptomatic nocturnal enuresis (MNE) and evaluate whether these factors can be used as biomarkers for the treatment outcome. METHODS: NGF and BDNF levels were measured and compared in 38 children (28 boys and 10 girls) with MNE and 25 children (18 boys and 7 girls) with no urinary symptoms were assessed. The mean ages in the patient and control groups were 9 and 10 years, respectively (P = .49). The patients were treated with either alarm or desmopressin therapy. RESULTS: The urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in the patient group than in the control group (P = .0003 and P = .0095, respectively). NGF and BDNF levels showed a significant positive correlation (P = .0020, r = 0.40). With respect to the degree of response, 19 patients (50%) showed complete response (CR) or partial response (PR), and 19 patients (50%) showed nonresponse (NR). The urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in the NR group than in the CR and PR groups (P = .0003 and P = .0003, respectively). CONCLUSIONS: Urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in children with MNE than in healthy controls. Urinary NGF/creatinine can be predictive factors of a poor treatment outcome in children with MNE.

BDNF and NGF gene polymorphisms and urine BDNF-NGF levels in children with primary monosymptomatic nocturnal enuresis.

INTRODUCTION: The pathophysiology and genetic influences in nocturnal enuresis have not been fully elucidated. Delayed neuronal maturation has been suggested as a pathogenetic mechanism in primary monosymptomatic nocturnal enuresis (PMNE). Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are neurotrophins affecting maturation of the nervous system. OBJECTIVE: The aim of this preliminary study was to investigate BDNF and NGF gene polymorphisms and urine levels of BDNF and NGF in children with PMNE as a first time. STUDY DESIGN: The single-nucleotide polymorphisms of BDNF (rs6265:G > A:Val66Met; rs8192466:C > T:Thr2Ile) and NGF (rs6330:C > T:Ala35Val, rs11466112:C > T:Arg221Trp) were investigated by comparing 104 children with PMNE and 140 healthy control subjects. Children with non-PMNE were excluded. DNA isolation and detection of polymorphisms were performed by real-time polymerase chain reaction. In addition, urine BDNF and NGF levels of 47 PMNE and 29 healthy children were measured by enzyme-linked immunosorbent assay method and normalized to urine creatinine (Cr) concentration for comparisons. RESULTS: There were no differences in genotype and allele frequencies of BDNF rs6265 and NGF rs6330 polymorphisms between patients with PMNE and the control group (P > 0.05). No mutant alleles were found in BDNF rs8192466 and NGF rs11466112 polymorphisms in either group. Children with PMNE had higher urine BDNF/Cr (0.020 ± 0.010 vs 0.010 ± 0.002; P = 0.008) and NGF/Cr ratio (3.01 ± 1.87 pg/mg vs 1.77 ± 0.26 pg/mg; P = 0.002) compared with the control subjects. However, no significant differences were found in BDNF/Cr and NGF/Cr values between GG, GA, and AA genotypes of BDNF rs6265 polymorphism and CC and CT genotypes of NGF rs6330 polymorphism (P > 0.05). DISCUSSION: In this study, no association of BDNF and NGF gene polymorphisms with PMNE was found, and urine neurotrophin concentrations were not directly influenced by investigated polymorphisms. Although, previously increased urine neurotrophin secretion has been found in detrusor overactivity, bladder inflammation, and dysfunctional voiding, this preliminary results also showed an increase in neurotrophins in PMNE. Higher urine neurotrophin levels may be related to delayed and continued neuronal maturation or increased production of neurotrophins in the bladder. The increased urine neurotrophins in PMNE may be an indicator of increased sensory nerve excitability of the bladder, contributing to the development of enuresis. CONCLUSION: This study showed that investigated neurotrophin gene polymorphisms did not make a significant contribution to the development of PMNE, but urine levels of neurotrophin gene products were higher in PMNE. Owing to the complexity and heterogeneity of genotype-phenotype relationships in enuresis, further studies are needed in PMNE.

Claiming desmopressin therapeutic equivalence in children requires pediatric data: a population PKPD analysis.

PURPOSE: For a new formulation of a drug, only pharmacokinetic bioequivalence with the original formulation has to be demonstrated in healthy, young adults. However, "children are not small adults," and to guarantee a safe and effective treatment, age-adapted drug development is required. Desmopressin, a vasopressin analogue prescribed for nocturnal enuresis in children, was studied as an example formulation first developed in adults and then extrapolated to a pediatric indication. METHODS: Population pharmacokinetic and pharmacodynamic modeling was used to analyze previously published desmopressin data of 18 children suffering from nocturnal enuresis. The main objective was the comparison of the therapeutic equivalence of two desmopressin formulations: tablet and lyophilisate. The measurements for pharmacokinetics and pharmacodynamics were respectively plasma desmopressin concentration and urine osmolality and diuresis. RESULTS: The half maximal inhibitory concentration for inhibition of urine production was 0.7 pg/mL lower for the lyophilisate than for the tablet. The effect of formulation on the half maximal inhibitory concentration seems to suggest that the 120-µg lyophilisate has a more pronounced effect on the urine volume and osmolality than the 200-µg tablet, even when the same exposure is achieved. CONCLUSIONS: A new indirect response model for desmopressin was constructed and validated, using a previously built pharmacokinetic model and additional pharmacodynamic data. In order to draw solid conclusions regarding the efficacy and safety of desmopressin in children, pharmacokinetics and pharmacodynamics data should be analyzed together. This study adds proof to potential differences in pediatric and adult pharmacokinetic and pharmacodynamic properties of desmopressin and exemplifies the need for pediatric clinical trials, not only for every new drug but also for every new formulation.

Evaluation of Urinary Aquaporin 2 and Plasma Copeptin as Biomarkers of Effectiveness of Desmopressin Acetate for the Treatment of Monosymptomatic Nocturnal Enuresis.

PURPOSE: Desmopressin is a synthetic V2 specific analogue of antidiuretic hormone (arginine vasopressin) that is widely used as first line treatment for monosymptomatic nocturnal enuresis. However, no biomarkers to predict desmopressin effectiveness have yet been established. Because arginine vasopressin is unstable, we prospectively measured the major urine concentration factor aquaporin 2 and serum copeptin (as a surrogate marker for vasopressin) in patients with monosymptomatic nocturnal enuresis, and evaluated whether they are useful for predicting desmopressin treatment outcome. MATERIALS AND METHODS: The study included 32 children 6 to 11 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria. Exclusion criteria were daytime urinary symptoms and underlying diseases causing nocturnal enuresis. Subjects were treated with 120 µg or 240 µg desmopressin oral disintegrating tablet and were divided into responders (at 120 or 240 µg) and nonresponders (at 240 µg). Day/night ratios of plasma copeptin and urinary aquaporin 2 were measured during desmopressin treatment. RESULTS: There was no significant difference in baseline day/night ratio of urinary aquaporin 2 between desmopressin responders and nonresponders. After 8 weeks of treatment there was a significant correlation between day/night ratio of aquaporin 2 and percentage of wet nights. In responders (but not nonresponders) there was a significant difference in the change in aquaporin 2 day/night ratio from before treatment to complete remission (p = 0.0004). For plasma copeptin the baseline day/night ratio for responders at 120 µg was significantly lower than in the 240 µg nonresponder group (p = 0.02). CONCLUSIONS: Urinary aquaporin 2 appears to be a biomarker of desmopressin treatment effectiveness during therapy, while plasma copeptin levels before treatment are predictive of desmopressin response.

Basic or extended urine sampling to analyse urine production?

BACKGROUND: Frequency volume charts are valuable tools to objectify urine production in patients with nocturia, enuresis or nocturnal incontinence. Analyses of daytime and nighttime urine (=basic collection) or analyses of urine samples collected every 3 h (=extended collection) extend this evaluation by describing circadian patterns of water and solute diuresis (=renal function profiles). AIM: To assess intra-individual correlation and agreement between renal function profiles provided using basic and extended urine collections, and using two extended urine collections. To create a short-form of the extended collection. METHODS: This prospective observational study was executed at Ghent University Hospital, Belgium. Study participation was open for anyone visiting the hospital. Participants collected one basic and two extended 24-h urine collections. Urinary levels of osmolality, sodium and creatinine were determined. RESULTS: There was a moderate to strong correlation between results of basic and extended urinalyses. Comparing both extended urinalyses showed a moderate correlation between the eight individual samples and a weak to strong correlation between the mean daytime and nighttime values of renal functions. Different samples could be considered as most representative for mean daytime values, while all samples collected between 03 and 05am showed the highest agreement with mean nighttime values of renal function. CONCLUSION: Since there is a good correlation and agreement between basic and extended urine collections to study the mechanisms underlying urine production, the choice of urine sampling method to evaluate urine production depends on the purpose. A nighttime-only urine sample collected between 03 and 05am may be the most practical approach.

Hypercalciuria in children with monosymptomatic nocturnal enuresis.

OBJECTIVE: The aim of this study was to measure the 24 h urinary calcium content in children with monosymptomatic nocturnal enuresis (MNE) and compare with those in healthy children to investigate whether there is any relation with enuresis and hypercalciuria. MATERIAL AND METHODS: This study included 120 children and adolescents with MNE aged between 7 and 14 years. Eighty age- and sex-matched healthy children served as a control group. To determine urinary calcium excretion, 24 h urine samples were collected. The children with enuresis were divided into two sub-groups as hypercalciuric and normocalciuric groups according to the amount of urinary calcium excretion. RESULTS: Hypercalciuria was found in 27 (23%) of the MNE patients compared with two (4%) of continent children (p<0.001). In addition, the mean 24 h urine calcium/body weight ratio was higher in the enuresis group than in the control group, 2.94±2.42 versus 1.59±1.72, respectively (p=0.002). When the children with enuresis were divided into two groups as normokalsiuric and hypercalciuric, the hypercalciuric children were younger and the majority of this group were boys.. CONCLUSIONS: Our study showed that hypercalciuria is common in children with MNE, so we suggested measuring urine calcium levels in NE patients. However, further studies are needed to clarify the relationship between hypercalciuria and NE in larger series..

Urinary glycosaminoglycan excretion in patients with primary nocturnal enuresis.

AIM: The aim of this study was to determine whether primary nocturnal enuresis (PNE) leads to alterations in glycosaminoglycan (GAG) excretion. METHODS: Twenty subjects (mean age 8.7 years, M/F 15/5) with PNE were included in the study. Twenty-two healthy subjects were selected as a control group (mean age 8.7 years, M/F 14/8). Urinary GAG excretion was measured using a modified dimethylmethylene blue (DMD) assay of 24-hour urine. RESULTS: The mean urinary GAG content was 33.9 mg/g and 23.8 mg/g creatinine in patients with PNE and controls, respectively; patients with PNE thus had a higher mean GAG excretion than did age-matched controls (p < 0.05). The association between GAG level and enuresis frequency bordered on significance (p = 0.068). CONCLUSIONS: GAG excretion in patients with PNE was significantly higher than in normal children, suggesting that measurement of urinary GAG may be useful in evaluating physiopathological conditions of the bladder wall. Further studies are needed to confirm this finding.

Nocturnal polyuria and nocturnal arginine vasopressin (AVP): a key factor in the pathophysiology of monosymptomatic nocturnal enuresis.

AIMS: To identify the relationship between nocturnal AVP deficiency, nocturnal polyuria (NP), and low urinary osmolality in children suffering of primary monosymptomatic nocturnal enuresis (NE). PATIENTS AND METHODS: The study included 50 children (28 males and 22 females) with primary monosymptomatic NE and 30 non enuretic children of the same age group (controls). Night samples of blood and urine were obtained for AVP, blood osmolality, and urine osmolality. In addition, volume frequency charts, arousal threshold, and urodynamics were performed for these children. RESULTS: Twenty eight (56%) of the enuretic children were considered to have NP. Mean AVP level was 44.80 +/- 8.19 and 32.49 +/- 18.25 pg/ml while mean urine osmolality was 865.07 +/- 158.66 mOsm/kg and 700.06 +/- 84.42 mOsm/kg in controls and enuretic group respectively. These differences were highly significant. No significant difference was found between the controls and enuretics without NP. On the other hand, nocturnal AVP and urine osmolality were significantly lower in enuretics with NP when compared to both controls and enuretics without NP. Blood osmolality did not reach statistically significant difference between subgroups. Arousal threshold was significantly higher in enuretic children irrespective to NP. The timing for NE episodes were predominantly late in the night in NE children without NP while patients suffering of NE with NP typically experienced multiple incidents each night. CONCLUSION: We have shown that low nocturnal AVP and urine osmolality may play a role in the pathophysiology of enuretics with NP. This abnormality doesn't occur as an isolated disease as these children suffer from arousal defect as well.

Increased excretion of glycosaminoglycans in children with urinary incontinence compared to those with monosymptomatic nocturnal enuresis.

OBJECTIVE: To analyse the urinary excretion of glycosaminoglycans (GAGs) in patients with either urinary incontinence or nocturnal enuresis. MATERIAL AND METHODS: The study population comprised 65 patients with either nocturnal enuresis (n=34) or urinary incontinence (n=31) and 67 controls. Excretion of urinary GAGs was assessed using the sodium tetraborate-carbazole method. RESULTS: GAG excretion in patients with urinary incontinence was significantly higher than that in controls (p<0.000129) and in children with nocturnal enuresis (p<0.016). There were no age or sex differences in GAG excretion in the three groups studied. CONCLUSION: Increased GAG excretion in patients with urinary incontinence suggests an association with urothelial/detrusor pathology.

Evaluation of a cure process during alarm treatment for nocturnal enuresis.

Using a treatment package featuring the urine alarm, this study evaluated a treatment process for nocturnal enuresis. Children who received the training were classified into treatment successes (N = 38) and nonsuccesses (N = 19) according to a criterion (3-week continence). Their daily results were analyzed with four categories: dry with sleep (DS), dry with spontaneous awakening (DA), wet with spontaneous or alarm-forced awakening (WA), and wet with sleep (WS). In a trend analysis, an increase of DA over the treatment process was prominent for successes compared to nonsuccesses. Entering WA to a discriminant analysis, 86% of children were correctly classified into the two groups. The findings that awakening categories well distinguished successes from nonsuccesses provide support for an active avoidance model explaining the efficacy of urine-alarm treatment for nocturnal enuresis.