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.

Urinary calcium excretion in children with monosymptomatic enuresis.

BACKGROUND: Among many factors predisposing to monosymptomatic enuresis (MNE) disturbances in urinary electrolites excretion play an important role. Because of many controversies in this field there is a need to debate the role of hypercalciuria in MNE. The aim of our study was to determine the urinary calcium in children with MNE. METHODS: The investigation was conducted on 204 children (83 MNE children and 121 reference group). Urinary calcium excretion (in 24-h collection and per kg of body mass), Ca/creatinine ratio, Ca(2+) in urine sample and in 24-h collection of urine were estimated. RESULTS: Hypercalciuria in MNE group was diagnosed in 18/83 (21.69%) patients. We found statistically significant differences between children with MNE in Ca(2+) in urine sample and 24-h collection and Ca/creat. ratio. Median urinary calcium excretion (mg/kg/24-h and mmol/24-h) was significantly higher in hypercalciuric enuretic patients. The urinary total calcium (mmol/24-h), urinary bound calcium and urinary calcium concentration (mmol/L) demonstrated a significant positive correlation with height, weight and age in reference group but not in MNE group. CONCLUSION: Urinary calcium excretion was significantly disturbed and further studies are needed to assess the role of hypercalciuria in the pathogenesis of MNE.

Urinary calcium excretion in healthy children and children with primary monosymptomatic nocturnal enuresis.

PURPOSE: We investigated the role of urinary Ca excretion in monosymptomatic nocturnal enuresis, and defined normality and intra-individual variability in Ca excretion in healthy children. MATERIALS AND METHODS: We included 46 Danish children with desmopressin resistant nocturnal enuresis and 96 healthy controls. We performed fractional urine collections at home during 2 days in controls or during hospitalization in children with enuresis. Urine volume, osmolality, and Ca and creatinine measurements were performed and Ca-to-creatinine ratios were calculated and compared between groups. Based on nocturnal urine output children with enuresis were characterized as having polyuria (nocturnal urine volume greater than 130% of expected bladder capacity) or not having polyuria. RESULTS: We did not find any differences in controls compared with children with enuresis who did not and did have nocturnal polyuria in daytime Ca excretion (mean +/- SE 0.121 +/- 0.012, 0.078 +/- 0.014 and 0.095 +/- 0.020 mg/mg creatinine), nighttime Ca excretion (0.115 +/- 0.011, 0.092 +/- 0.019 and 0.139 +/- 0.029 mg/mg creatinine) or 24-hour Ca excretion (0.118 +/- 0.011, 0.083 +/- 0.014 and 0.106 +/- 0.020 mg/mg creatinine, respectively). Urinary Ca excretion was not influenced by patient age, sex or body weight and, furthermore, we did not find evidence of diurnal variation. However, we observed considerable intra-individual variability in diurnal, nocturnal and total 24-hour urinary Ca-to-creatinine ratios. CONCLUSIONS: These observations contradict several previous reports and speculations on a role of Ca in the pathogenesis of nocturnal enuresis.

Circadian variation of angiotensin II and aldosterone in nocturnal enuresis: relationship to arterial blood pressure and urine output.

PURPOSE: We investigated the circadian rhythm of solute excretion and regulating hormones as well as blood pressure in patients with monosymptomatic nocturnal enuresis. MATERIALS AND METHODS: We included 15 patients with a mean age +/- SE of 13.4 +/- 0.9 years who had monosymptomatic nocturnal enuresis with at least 3 wet nights weekly and a control group of 10 healthy children with a similar age and sex distribution. During inpatient circadian studies urine was collected during 6 periods and blood was drawn at 7 time points during 24 hours. Heart rate and blood pressure was recorded with an ambulatory blood pressure monitor every 30 to 60 minutes. RESULTS: The total patient group excreted a significantly larger nocturnal urine volume than controls (p <0.01). Five patients had marked nocturnal polyuria (nocturnal urine volume greater than the mean in the control group +2 SD), whereas urine output in the remaining patients without polyuria were similar to controls. Nocturnal polyuria was caused mainly by increased nocturnal solute excretion, especially Na. Serum aldosterone and plasma angiotensin II showed a marked circadian rhythm in normal children with a nocturnal increase concomitant with a significant decrease in mean arterial blood pressure during sleep. In contrast, the group of patients with nocturnal polyuria showed a lack of circadian rhythm in all excretion variables as well as an attenuated rhythm in plasma angiotensin II and mean arterial blood pressure. Interestingly this group had normal circadian rhythms of the circadian rhythm markers plasma cortisol and heart rate. CONCLUSIONS: The study suggests that an abnormally large nocturnal excretion of Na caused by selectively attenuated circadian rhythms of Na regulating hormones might be an important pathogenic factor in monosymptomatic nocturnal enuresis.

[Study of renal morphology and function in children with nocturnal enuresis. Relationship with sensitivity or resistance to desmopressin]. / Estudio de la morfología y la función renal en niños diagnosticados de enuresis nocturna. Su relación con la sensibilidad o la resistencia a la desmopresina.

BACKGROUND: In the last few years, there have been reports that children with nocturnal enuresis frequently have hypercalciuria. Likewise, children with desmopressin-resistant enuresis have recently been reported to have a higher renal concentration capacity than patients with desmopressin-sensitive enuresis. OBJECTIVES: To study renal function and urinary calcium excretion and to register familial history of enuresis and urolithiasis in a group of children with enuresis, whether responders or nonresponders to desmopressin, followed-up in our hospital. MATERIAL AND METHODS: A cohort of 60 patients (42 boys and 18 girls) who were referred to the hospital because of nocturnal enuresis. RESULTS: Hypercalciuria was detected in 26 children (43.3 %) and hypocitraturia in eight (13.3 %). The frequency of hypercalciuria was higher in desmopressin-resistant patients than in desmopressin-sensitive patients, but this difference was not statistically significant. Sonographic renal morphological anomalies were detected in 11 children (18.3 %). No differences in renal handling of water were detected when the patients were distributed according to the grade of sensitivity to desmopressin. CONCLUSIONS: In our cohort we found a high frequency of hypercalciuria in children with nocturnal enuresis. No differences were observed in maximal urinary osmolality among desmopressin-resistant and desmopressin-sensitive children.

The role of urine osmolality and ions in the pathogenesis of primary enuresis nocturna and in the prediction of responses to desmopressin and conditioning therapies.

Aim of the study was to determine the role of nocturnal and daytime urine volume, osmolality and ion excretions in the pathogenesis of primary monosymptomatic enuresis nocturna (PMEN) and in the prediction of response to desmopressin and conditioning therapies. Fifty-five children with PMEN between the ages 5 and 15 years were included to the study. The patients were randomly divided into three groups Group 1: Twenty enuretics having intranasal desmopressin 1x 20 microg treatment for 2 months Group 2: Twenty enuretics having conditioning therapy for 2 months. Group 3: Fifteen enuretics having intranasal izotonic solutions as placebo. The control group consisted of 15 healthy children. Urine osmolality, sodium, potassium, chloride, magnesium and creatinine levels were investigated in both daytime and nighttime urines. Fractional sodium, potassium, magnesium, chloride excretions were calculated. Wilcoxon, Mann-Whitney U, Kruskal-Wallis, Chi-square, Student's t and Pearson correlation tests were performed. The ratio of night/daytime urine osmolality was significantly decreased in enuretic children. In addition, the ratio of night/daytime urine Cl and K excretions were also significantly decreased in enuretics. Response rate to desmopressin and conditioning treatments were statistically higher than placebo control. The difference between response rates of desmopressin and conditioning therapies was not found statistically significant. Pretreatment values of urine volume osmolality and ions were not observed as predictive factors in response to desmopressin or conditioning therapy. In conclusion, nightly decreased potassium and chloride excretions were found to have a role in the pathogenesis of primary enuresis nocturna. Urine volume, osmolality and ion excretions are not suggested to be used in the prediction of response to desmopressin and conditioning therapies.

Estudio de la morfología y la función renal en niños diagnosticados de enuresis nocturna. Su relación con la sensibilidad o la resistencia a la desmopresina / Study of renal morphology and function in children with nocturnal enuresis. Relationship with sensitivity or resistance to desmopressin

Antecedentes: En los últimos años, se ha descrito que, con frecuencia, los niños con enuresis nocturna presentan hipercalciuria. Así mismo, se acaba de comunicar que los niños con enuresis nocturna resistente a desmopresina tienen una capacidad de concentración renal superior a la de aquellos pacientes con enuresis sensible a ese fármaco. Objetivos: Estudiar la función renal y la eliminación urinaria de calcio y registrar los antecedentes familiares de enuresis y de litiasis en un grupo de niños enuréticos respondedores y resistentes a desmopresina controlados en nuestro hospital. Material y métodos: Cohorte de 60 pacientes, 42 varones y 18 mujeres, que fueron remitidos al hospital por padecer enuresis nocturna. Resultados: Se detectó hipercalciuria en 26 niños (43,3 %) e hipocitraturia en ocho (13,3 %). La frecuencia de hipercalciuria fue superior en los pacientes resistentes con respecto a los sensibles a desmopresina, sin diferencias estadísticamente significativas. En 11 niños se detectaron anomalías morfológicas ecográficas renales. No se comprobaron diferencias en el manejo renal del agua al distribuir a los pacientes según el grado de sensibilidad a la desmopresina. Conclusiones: En nuestra serie se demuestra la elevada frecuencia de hipercalciuria en niños con enuresis nocturna. No observamos diferencias en la osmolalidad urinaria máxima entre los niños sensibles y los resistentes a la desmopresina

Background: In the last few years, there have been reports that children with nocturnal enuresis frequently have hypercalciuria. Likewise, children with desmopressin-resistant enuresis have recently been reported to have a higher renal concentration capacity than patients with desmopressin-sensitive enuresis. Objectives: To study renal function and urinary calcium excretion and to register familial history of enuresis and urolithiasis in a group of children with enuresis, whether responders or nonresponders to desmopressin, followed-up in our hospital. Material and methods: A cohort of 60 patients (42 boys and 18 girls) who were referred to the hospital because of nocturnal enuresis. Results: Hypercalciuria was detected in 26 children (43.3 %) and hypocitraturia in eight (13.3 %). The frequency of hypercalciuria was higher in desmopressin-resistant patients than in desmopressin-sensitive patients, but this difference was not statistically significant. Sonographic renal morphological anomalies were detected in 11 children (18.3 %). No differences in renal handling of water were detected when the patients were distributed according to the grade of sensitivity to desmopressin. Conclusions: In our cohort we found a high frequency of hypercalciuria in children with nocturnal enuresis. No differences were observed in maximal urinary osmolality among desmopressin-resistant and desmopressin-sensitive children

Asymptomatic bacteriuria in men with orthotopic ileal neobladders: possible relationship to nocturnal enuresis.

OBJECTIVE: To assess prospectively the incidence with time of asymptomatic bacteriuria in patients with orthotopic ileal neobladders, and the possible effect on neobladder function. PATIENTS AND METHODS: In all, 47 patients (mean age 52.7 years, sd 8.7, range 31-68) with uncomplicated orthotopic ileal neobladders were prospectively evaluated. With no antibiotic manipulation, consecutive urine cultures were assessed monthly. Continence was assessed by direct information from the patients at each follow-up visit. RESULTS: Overall, 797 samples were cultured from the 47 patients (mean 17.6, sd 7.1). There was a steady decrease in the incidence of positive cultures, from 74.5%, to 35.6% and 6.7% at 1, 6 and 18 months, respectively. While there was persistently sterile urine in only eight patients (17%), 32 had occasional and seven had persistent bacteriuria. Escherichia coli was the commonest organism (76.6%) followed by Klebsiella pneumonia (15.7%); 54% of E. coli and 38% of K. pneumonia infections were sensitive to nitrofurantoin. Diurnal continence was achieved in 98% of the patients at 6 months after surgery. There was a gradual decrease in the frequency of nocturnal enuresis (NE) with time, from 87%, to 42%, 28% and 27% at 1, 6, 12 and 18 months, respectively. There was a significant correlation between the presence of bacteriuria and NE during the first 6 months, but it was not sustained after that. The age of the patients was also related significantly to the incidence of NE; at 6 months, only one of 18 men aged < or = 50 years had NE, while 19 of 29 aged > 50 years had (P < 0.001). At 1 year all patients aged < or = 50 years were nocturnally continent, while half of those aged > 50 years had NE (P = 0.001). CONCLUSIONS: Ileal neobladders are associated with a high incidence of asymptomatic bacteriuria during the first year after surgery. There was spontaneous clearance of bacteriuria with time, with no antimicrobial manipulation. Soon after surgery there was a significant association between bacteriuria and NE. The effect of antimicrobials on patients with NE should be evaluated.

Functional bladder capacity and urine osmolality in children with primary monosymptomatic nocturnal enuresis.

OBJECTIVE: To assess functional day-time bladder capacity (DBC) and urine osmolality in children with primary monosymptomatic nocturnal enuresis (PMNE) according to age and sex. MATERIAL AND METHODS: A total of 263 children with PMNE were divided into two groups: Group I, 160 children (63 girls, 97 boys) aged 5-9 years (mean age 7.14+/-1.47 years); and Group II, 103 children (25 girls, 78 boys) aged 10-15 years (mean age 12.26+/-1.52 years). DBC (milliliters) was the largest void of the day measured over four 24-h periods, irrespective of the diet applied. Urine osmolality was determined three times: in the evening before bed-time; at night, 2-4 h after falling asleep; and in the morning in the nocturnal void. RESULTS: DBC was smaller in Group I than in Group II (151.27 vs 199.46 ml; p<0.05). No statistically significant differences were found in relation to sex (p>0.05). The mean osmolality of the nocturnal void in the morning was 854.15 and 909.22 mOsmol/kg H(2)O in Groups I and II, respectively (p>0.05). Differences between boys and girls were not statistically significant (p>0.05). No correlation was found between DBC and urine osmolality (p>0.05). A detailed analysis of the results revealed DBC below the 5th percentile or above the 95th percentile in 23/263 cases (8.7%), reduced osmolality (< 800 mOsmol/kg H(2)O) in 76/263 (28.8%), a familial nature of nocturnal enuresis in 124/263 (47.1%) and difficulty waking in 86/263 (32.7%). CONCLUSIONS: In children with PMNE aged 5-15 years, functional DBC increases with age and does not differ between the sexes; the mean nocturnal urine osmolality is neither age- nor sex-dependent.

Sodium fraction excretion rate in nocturnal enuresis correlates with nocturnal polyuria and osmolality.

PURPOSE: We verify the sodium fraction excretion rate (FE Na) and potassium fraction excretion (FE K) rates in monosymptomatic nocturnal enuresis. We also correlate FE Na and FE K to urinary osmolality, nocturnal polyuria and vasopressin in the same population. MATERIALS AND METHODS: A total of 438 children 6 to 15 years old (mean age 9.7) presenting with monosymptomatic nocturnal enuresis were recruited from different centers. Inclusion criteria were 3 or greater wet nights a week, no daytime incontinence and no treatment in the previous 2 months. Exclusion criteria were cardiopathy, endocrinopathy, psychiatric problems and urinary tract abnormalities. Micturition chart, diurnal (8 am to 8 pm) and nocturnal (8 pm to 8 am) urine collection, including separate diuresis volumes, (Na, K and Ca) electrolytes and osmolality were evaluated, as well as serum electrolytes, creatinine and nocturnal (4 am) vasopressin. Diurnal and nocturnal FE K and FE Na were calculated. ANOVA test, chi-square test, Student's t test and Pearson correlation test were used for statistical analysis. RESULTS: : Nocturnal polyuria (diurnal to nocturnal diuresis ratio less than 1) was found in 273 children (62.3%, group 1 and nocturnal urine volumes were normal in 165 with enuresis (37.7%, group 2). Nocturnal FE Na was abnormal in 179 children (40.8%), including 118 in group 1 (43.2%) and 61 in group 2 (36.9%) (chi-square not significant). FE Na was also increased in nocturnal versus daytime diuresis (Student's t test p <0.001). In group 1 nocturnal FE Na correlated with nocturnal diuresis (Pearson correlation p = 0.003, r = +0.175), while daytime FE Na and nocturnal FE Na correlated with diurnal diuresis (Pearson correlation p = 0.001, r = +0.225 and Pearson correlation p = 0.001, r = +0.209, respectively). In group 2 nocturnal FE Na did not correlate with diuresis (Pearson correlation p = 0.103, r = +0.128) but correlated with vasopressin values (Pearson correlation p = 0.042, r = -0.205). Urine osmolality was reduced in 140 children (31.9%) and correlated with nocturnal diuresis (Pearson correlation p = 0.003, r = -0.321). Vasopressin was decreased in 332 children (75.8%, 62.6% in group 1 and 13.2% in group 2). No significant difference was found between sexes and age of enuretic subgroups. CONCLUSIONS: Nocturnal FE Na correlates with nocturnal diuresis, whereas daytime FE Na does not. FE K in daytime and nighttime diuresis does not statistically differ in nocturnal polyuric and nonpolyuric enuretic groups. Osmolality correlates with nocturnal diuresis, and vasopressin at 4 am was lower in the nocturnal polyuric group. The hypothesis of a subset of enuretic patients presenting with nocturnal polyuria associated with high nocturnal natriuria and low vasopressin values has been confirmed.

Increased urinary calcium excretion in enuretic children treated with desmopressin.

PURPOSE: The use of desmopressin in the treatment of primary nocturnal enuresis (PNE) is accepted and based on the fact that this drug leads to renal water reabsorption. However, recent findings have also implicated that desmopressin regulates other molecules, such as sodium and potassium. We investigate if desmopressin influences renal Ca2+ handling. MATERIALS AND METHODS: A total of 32 children with PNE were enrolled in a prospective study. Patients received a standard 30 microg desmopressin intranasally before going to bed. All patients were treated for at least 4 weeks. Desmopressin was then withdrawn and reintroduced after 2 weeks. Urine samples were collected during all 3 phases of the study. Ca2+ measurement was performed in single morning spot urines as well as in 24-hour collections. Additionally, blood was sampled for analysis of Ca2+. The Wilcoxon signed rank test was used for statistical analysis. RESULTS: Wet nights decreased an average of 4.75 to 1.0 per week with desmopressin treatment. While blood concentrations did not change with or without medication, urinary Ca2+ excretion was significantly higher while patients were treated with desmopressin. This significant result was the same in single spot as well as in 24-hour samples. CONCLUSIONS: This study demonstrated the increased excretion of Ca2+ by desmopressin treatment in children with PNE. Since Ca2+ is a crucial molecule in growth and development, this finding indicates the necessity of larger followup studies concerning Ca2+ handling and growth in children on long-term desmopressin treatment.

Enuresis subtypes based on nocturnal hypercalciuria: a multicenter study.

PURPOSE: Desmopressin may not be effective for nocturnal enuresis associated with polyuria and hypercalciuria. Nighttime hypercalciuria in an enuretic population from 5 centers and its correlation with nighttime polyuria were verified. MATERIALS AND METHODS: A total of 450 enuretic patients (278 males, 172 females, mean age 9.7 years) were evaluated with 72-hour micturition charts, urinalysis, serum creatinine and osmolarity, diurnal and nocturnal electrolytes with fractional Na+ and K+ urinary excretion, and nocturnal (4 a.m.) plasma vasopressin. Creatinine electrolytes and osmolarity were measured in daytime (8 a.m. to 8 p.m.) and nighttime (8 p.m. to 8 a.m.) urine volumes. Patients were divided into group 1 with nocturnal polyuria and group 2 without nocturnal polyuria. Hypercalciuria was defined as urinary calcium-to-urinary creatinine ratio greater than 0.21. Statistic evaluation was performed using chi-square, Pearson correlation and ANOVA tests. RESULTS: Nighttime polyuria was demonstrated in 292 bedwetters (65% group 1). Nocturnal hypercalciuria was present in 179 of the 450 children (39.7%), including 125 in group 1 (42.8%) and 54 in group 2 (34.2%), which was statistically significant (chi-square p = 0.008, Pearson correlation test r = 0.157). Daytime calciuria was not statistically modified in either group (group 1 p = 0.054, group 2 p = 0.56). Adrenocorticotropic hormone (ADH) was normal in 18.5% and low in 81.5% of enuretics with nocturnal hypercalciuria. ADH levels and nocturnal hypercalciuria significantly correlated (p = 0.003, r = 0.148). Conversely, the group 2 patients had normal ADH levels. CONCLUSIONS: Nocturnal hypercalciuria has a pivotal role in nocturnal enuresis, as it is significantly associated with low ADH levels and nocturnal polyuria. A new classification of nocturnal enuresis subtypes based on nighttime calciuria levels is mandatory to address treatment properly.

Low-calcium diet in hypercalciuric enuretic children restores AQP2 excretion and improves clinical symptoms.

In this study, we analyzed the effect of a therapeutic intervention in 46 enuretic children, 26 (57%) of whom were hypercalciuric. All the patients (n = 46) were treated with DDAVP for 3-6 mo. The hypercalciuric patients (n = 26) received a low-calcium diet (approximately 500 mg/day) for the same period. After the therapy, the bed-wetting episodes stopped in 80% of the 46 patients tested. In those patients having low-AVP levels before the therapy, circulating AVP concentration returned to normal (>4 pg/ml), and the hypercalciuria was resolved in the hypercalciuric patients (calcium/creatinine ratio <0.2). Urinary aquaporin-2 (AQP2) levels were semiquantified by densitometric scanning and reported as a ratio between the intensity of the signal in the day vs. the night urine samples (day/night AQP2 ratio). In the hypercalciuric patients, the day/night AQP2 ratio returned to values close to those found in the healthy children (from 1.19 +/- 0.20 before to 0.69 +/- 0.10 after the treatment, n = 26, P = 0.03). In contrast, in the normocalciuric children we saw no significant modulation of AQP2 excretion (from 1.07 +/- 0.14 before to 0.99 +/- 0.14 after the treatment, n = 20). This study clearly demonstrates that urinary calcium levels modulate AQP2 excretion and is likely to be useful for treatment of children with enuresis.

Increased urinary nitrite excretion in primary enuresis: effects of indomethacin treatment on urinary and serum osmolality and electrolytes, urinary volumes and nitrite excretion.

OBJECTIVE: To assess urinary nitrite excretion, a stable end product of nitric oxide (NO), in patients with enuresis and in normal controls, and to evaluate the effects of indomethacin (a potent prostaglandin synthesis inhibitor) on urinary nitrite excretion, other urinary variables and bladder capacity. PATIENTS AND METHODS: The study comprised 10 patients with primary enuresis and 10 normal comparable controls (age range 6-14 years). Nitrite was assayed in 'spot' morning urine samples in both the enuretics and normal controls. Enuretics were then given 50 mg indomethacin suppositories each night; urine volume, urinary osmolality and electrolytes, serum osmolality and electrolytes and urinary nitrite were assayed before indomethacin treatment and after 15 days of treatment. RESULTS: The mean (sd) urinary nitrite excretion was 24.4 (19.6) micromol/L in normal children and 275.9 (111.2) micromol/L in enuretics (P<0.05). With indomethacin, the urinary nitrite concentration was significantly decreased to 141 (45.1) micromol/L (P<0.05) and associated with a significant reduction in bed-wetting episodes and voiding frequency. The functional bladder capacity was <70% of the predicted value for age in six of the patients; they had significant improvements on indomethacin, to values similar to those in patients with a nearly normal functional bladder capacity. Indomethacin decreased the 24-h urinary volume by 41%, the night volume by 40%, clearance of free water by 46% and increased the day : night urinary volume ratio by 55%. The absolute amounts of urinary calcium, magnesium, phosphorus, urea, creatinine, and glucose were lower on indomethacin, although not statistically significantly so. Indomethacin decreased the 24-h urinary and 'spot' morning osmolality and osmotic clearance. There were no significant changes in serum osmolality and electrolyte concentrations. Indomethacin also decreased the absolute amount of urinary sodium, chloride and potassium, fractional sodium and potassium excretion, and filtered sodium. Creatinine clearance was decreased by 20% (P>0.05) and normal 24-h urinary protein was significantly lower, by 47%, after indomethacin treatment (P<0.05). CONCLUSION: Urinary nitrite excretion increased significantly in patients with primary nocturnal enuresis; indomethacin markedly reduced bed-wetting episodes and decreased the frequency of voiding in enuretics with small or normal functional bladder capacity, which was associated with a significant decrease in urinary nitrite excretion. Indomethacin reduced bed-wetting by decreasing the urine volume, clearance of free water and urinary electrolytes, and through possible effects on bladder and urethral contraction, by inhibiting NO and prostaglandin synthesis. NO and prostaglandins might be important in the pathogenesis of primary enuresis.

Urinary aquaporin-2 excretion in nocturnal enuresis.

OBJECTIVE: To evaluate the role of the arginine vasopressin (AVP)-aquaporin-2 (AQP-2) axis in the pathogenesis of nocturnal enuresis. STUDY PARTICIPANTS: Twelve children (seven male and five female), aged 11.6+/-4.3 (6.7-15.6) years, suffering from primary monosymptomatic nocturnal enuresis and 12 healthy children, matched for sex and age. Enuretic children were further subdivided into responders and non-responders to treatment with 1-desamino-8-d-AVP (DDAVP). METHODS: Serum concentrations of AVP, and plasma and urine osmolality were measured at night (0100, 0400 and 0700 h), together with nocturnal urinary excretion of AQP-2 (2000-0800 h). Magnetic resonance imaging (MRI) of the pituitary gland was carried out to evaluate the amount of AVP stored in the posthypophysis. RESULTS: Mean AVP serum concentrations were similar in patients and controls. Urinary AQP-2 was also similar in patients and controls, but responders had a significantly lower level of AQP-2 than non-responders (P<0.005). Plasma osmolality was greater in patients than in controls (P<0.001), whereas urinary osmolality was similar in both groups. No difference in the ratio of the signal intensity of the posterior lobe of the hypophysis to that of the pons (AVP content) was found between patients and controls or between responders and non-responders. CONCLUSION: A decreased urinary excretion of AQP-2 is associated with, and seems to have a role in, nocturnal enuresis, at least in some children, and this could also explain why only some of them respond to DDAVP treatment.

Urinary excretion of glycosaminoglycans in patients with isolated nocturnal enuresis or combined with diurnal incontinence.

OBJECTIVE: To determine variations in the amount of glycosaminoglycans (GAGs) excreted by patients with nocturnal enuresis and/or diurnal incontinence. PATIENTS, SUBJECTS AND METHODS: The study included 27 patients (aged 5-15 years) with nocturnal enuresis and/or diurnal incontinence, and 27 healthy age-matched children. Their urinary GAG excretion was assessed over 24 h using the sodium tetraborate-carbazole method. RESULTS: Patients with nocturnal enuresis and/or diurnal incontinence had higher mean values of urinary GAG excretion than age-matched controls. There were significant differences in GAG excretion between those with nocturnal enuresis and diurnal incontinence and those with nocturnal enuresis alone. CONCLUSIONS: GAG excretion in patients with nocturnal enuresis and/or diurnal incontinence was significantly higher than in normal children, suggesting that measuring urinary GAGs may be useful in evaluating physiopathological conditions of the bladder wall, and hence in monitoring potential damage in the bladder mucosa.

Urinary aquaporin 2 and calciuria correlate with the severity of enuresis in children.

This study examined the hypothesis that nocturnal enuresis might be paralleled by aquaporin 2 (AQP2) urinary excretion. Eighty children who experienced nocturnal enuresis were studied and compared with 9 healthy children. The 24-h urine samples were divided into two portions: night collections and day collections. Creatinine equivalents of urine samples from each patient were analyzed by Western blotting. AQP2 levels were semiquantified by densitometric scanning and reported as a ratio between the intensity of the signal in the day urine sample versus the night urine sample (D/N AQP2 ratio). The D/N AQP2 ratio was 0.59 +/- 0.11 (n = 9) in healthy children and increased to 1.27 +/- 0.24 (n = 10) in a subpopulation of enuretic children who had low nocturnal vasopressin levels. In enuretic children who displayed hypercalciuria and had normal vasopressin levels, the D/N AQP2 ratio was 1.05 +/- 0.27 (n = 8). These data indicate that reduced secretion of vasopressin and absorptive hypercalciuria are independently associated with an approximately twofold increase in the urinary D/N AQP2 ratio. When low nocturnal vasopressin levels were associated with hypercalciuria, a nearly threefold increase in the D/N AQP2 ratio was observed (1. 67 +/- 0.41, n = 11). In addition, in all enuretic patients tested, the urinary D/N AQP2 ratio correlates perfectly with the severity of the disorder (nocturnal polyuria). The findings reported in this article indicate that urinary AQP2 correlates with the severity of enuresis in children.

Night-time polyuria and urine hypo-osmolality in enuretics identified by nocturnal sequential urine sampling--do they represent a subset of relative ADH-deficient subjects?

Early morning urine osmolality was tested in two urinary specimens, one taken immediately upon awakening and the other approximately 30 min thereafter, in 52 enuretic and 15 non-enuretic children. In a follow-up study, using the same study population, urine osmolality and volume were measured sequentially at 3-h intervals at 19.00, 22.00, 01.00, 04.00 and 07.00 h. Thereafter, all enuretics were treated by intranasal DDAVP for a 6-month period. There were no differences in urinary osmolality between enuretic and non-enuretic children when comparing the two early morning specimens. Nor were there any differences between groups in urine osmolalities at 19.00, 01.00 and 07.00 h. In contrast, at 04.00 h, urine osmolality was significantly lower in 17 of 52 enuretics [designated as ADH-negative (ADH-)] compared to the remaining enuretics [designated as ADH-positive (ADH+)] and non-enuretic children (610 +/- 251 vs 995 +/- 195 and 1089 +/- 195 mosmol/kg H2O, respectively, p < 0.05). This decreased osmolality was paralleled by an increase in urine production during the time period 01.00-04.00 (83 +/- 24 vs 52 +/- 18 and 45 +/- 22 ml, respectively, p < 0.05). At the end of the 6-month period of DDAVP treatment, the percentage response was similar between the ADH- and ADH+ enuretics (79% vs 75%). However, the time taken to achieve a response was quicker in the ADH- subjects. These data suggest the existence of a subgroup of enuretics whose underlying pathophysiology is the development of nocturnal polyuria probably due to a relative night-time ADH deficiency. Nocturnal sequential monitoring of urinary osmolality, as described above, allows identification of this subgroup.