pituitrin and Enuresis

Enuresis was historically viewed as a primarily psychiatric disorder, but this understanding has changed dramatically since the end of the last century, when it became clear that somatic factors, such as nocturnal polyuria as a result of vasopressin deficiency, nocturnal detrusor overactivity and high arousal thresholds, all play a crucial role in enuresis pathogenesis. It has also become clear that enuresis is inherited in the majority of cases, although the correlation between genotype and enuretic phenotype is not straightforward. The standard view of enuresis as being the result of either (i) nocturnal polyuria and high arousal thresholds; or (ii) nocturnal detrusor overactivity and high arousal thresholds has become well-established, but further research now complicates the picture. First, psychological/psychiatric problems are overrepresented in enuresis, and might in a minority of cases have a causal or aggravating role. Second, nocturnal polyuria is not always linked to vasopressin deficiency. Third, nocturnal detrusor overactivity is in itself pathogenetically heterogeneous, and could be linked to constipation. Fourth, the sleep of enuretic children might be "deep," but possibly also disturbed (by obstructed airways or a distended or contracting bladder). These children might have high arousal thresholds because of the enuresis instead of the other way around. The same might possibly be said about nocturnal polyuria. Taking these new insights into account, a new model of enuresis pathogenesis is presented, which is more complicated but hopefully also more true than the standard consensus.

Topics: Adult; Antidiuretic Agents; Arousal; Central Nervous System; Child; Constipation; Deamino Arginine Vasopressin; Enuresis; Humans; Polyuria; Sleep; Urinary Bladder, Overactive; Vasopressins

Nocturnal enuresis is a benign condition, yet needs treatment to relieve the child and parents of the accompanying anxiety and the stigma attached to it. It is defined as normal nearly complete evacuation of the bladder at a wrong place and time at least twice a month after the fifth year of life. The underlying cause of enuresis is functional and various proposed pathophysiological mechanisms like maturational delay, genetics, role of sleep, antidiuretic hormone, and bladder capacity are discussed. These factors have a bearing on the management. As no treatment plan is ideal, various treatment modalities currently available including good supportive care are elaborated and a plan of management discussed.

Topics: Enuresis; Humans; Vasopressins

Topics: Adolescent; Child; Clinical Trials as Topic; Deamino Arginine Vasopressin; Enuresis; Follow-Up Studies; Humans; Long-Term Care; Renal Agents; Treatment Outcome; Vasopressins

The authors do not have all of the data about enuresis, and many children are subject to relapses or failure of treatment. There is no cause for despondency, however. Enuresis is no longer a mystery. Good data exist about the natural history, epidemiology, and etiology of enuresis. In addition, multiple treatment modalities are available to practitioners. This article has sought to review the scientific literature and to relate the authors' experience with enuresis. The authors recommend a treatment program for children with monosymptomatic nocturnal enuresis that includes removal of caffeine from the diet. Enuretic children do not consume enough fluid, and the authors recommend that the daily fluid requirement be divided during the day: 40% in the morning, 40% in the afternoon, and 20% in the evening, with no restriction of fluid. Normalization of small functional bladder capacities may help to cure enuresis and has an effect on the efficacy of other therapies. Treatment of enuretics with antibiotics is effective in children with UTI, bacteriuria, or cystitis cystica. DDAVP has been shown to be effective in the treatment of enuresis, especially in children who have achieved a normal functional bladder capacity. Bladder alarm systems also offer a potential cure of enuresis, are inexpensive, and show a low relapse rate.

Topics: Behavior Therapy; Child; Child Development; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Humans; Physical Examination; Renal Agents; Urinary Bladder; Urodynamics; Vasopressins

Childhood nocturnal enuresis has traditionally been regarded as a multifaceted problem with a variety of treatment interventions. This paper proposes a model based on the notion that nocturnal enuresis arises through the ill functioning of one or more of the following three systems - a lack of vasopressin release during sleep; bladder instability; and/or an inability to arouse from sleep to bladder sensations. Clinical signs of each system are outlined and the appropriate treatment intervention for each is discussed. It is argued that addressing nocturnal enuresis in this way will enhance overall treatment effectiveness.

Topics: Arousal; Child; Enuresis; Humans; Sleep Wake Disorders; Urinary Bladder; Vasopressins

Aquaporins are proteins that mediate transmembrane water transport in a variety of tissues including the kidney. Vasopressin plays an important role in regulation of water metabolism, and under normal conditions the kidney collecting duct is extremely sensitive to vasopressin. Vasopressin stimulates the synthesis of aquaporin 2 (AQP2) in kidney collecting duct principal cells. Studies in Brattle Boro rats which are vasopressin deficient, revealed low levels of AQP2 in association with extreme polyuria. After vasopressin treatment for 5 days AQP2 levels increased threefold. Using rat models with nephrogenic diabetes insipidus (NDI) we have demonstrated that AQP2 expression is down regulated in association with polyuria, suggesting that reduced levels of AQP2 may be a general factor in acquired forms of NDI from a variety of reasons. The polyuria and urinary concentrating defects associated with an abnormal nightly-increase in AVP in patients with nocturnal enuresis may partly be due to a lack of vasopressin-mediated AQP2 expression since treatment with desmopressin in these patients have normalised their nocturnal urine production.

Topics: Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Biological Transport; Cell Membrane; Diabetes Insipidus, Nephrogenic; Disease Models, Animal; Enuresis; Humans; Ion Channels; Polyuria; Rats; Rats, Brattleboro; Urinary Bladder; Vasopressins; Water-Electrolyte Balance

Body fluid homeostasis is maintained by the kidney. Such an accurate control in achieved via the secretion of antidiuretic hormone (ADH), the secretion of which is regulated by hypothalamic osmoreceptors. Both urine flow rate and the excretion of most electrolytes have a diurnal rhythm; they increase during daytime and decrease during nighttime. Such a rhythm seems to be absent in some subjects who suffer from bedwetting because of relative polyuria. In these cases, the polyuria is associated with a decreased nocturnal secretion of ADH and the subsequent excretion of dilated urine. A deficit in the nocturnal secretion of ADH thus appears to explain the response to desmopressin of children with a polyuric form of enuresis.

Topics: Child; Circadian Rhythm; Enuresis; Humans; Osmolar Concentration; Vasopressins

Topics: Bacteriuria; Enuresis; Humans; Urodynamics; Vasopressins

Prospective controlled studies on the treatment of enuresis with desmopressin (DDAVP) indicate that cure rates (complete dryness) while on therapy are markedly lower than are response rates (decrease in wet nights). In an attempt to explain this discrepancy, we analyzed the etiological mechanisms for enuresis and found evidence that most children are not cured by DDAVP because their nocturnal wetting is not actually caused by the defect which DDAVP therapy aims to cure: low nocturnal vasopressin secretion with high nocturnal urinary output. Our study suggested that an arrest in the normal development of two separate areas of the central nervous system is necessary for enuresis to occur in many patients, yet cure of enuresis occurs if either developmental delay is eliminated. This hypothesis of a dual developmental delay helps to unify many diverse and often seemingly contradictory scientific observations about this condition and to explain why many patients react inconsistently to treatment aimed at a single etiology, yet eventually become dry.

Topics: Circadian Rhythm; Deamino Arginine Vasopressin; Electroencephalography; Enuresis; Humans; Renal Agents; Sleep; Vasopressins

The efficacy of desmopressin in the treatment of functional enuresis, known for 15 years, has received very little attention in the psychiatric literature. This review seeks to remedy this and to asses critically its effectiveness, risks and side effects, as well as the implications for the understanding and management of enuresis.. Treatment trials, reports of unwanted effects, and literature on mechanisms of action were reviewed.. Desmopressin is more effective than placebo in controlled trials, but only one quarter of patients become "dry." Individuals who wet the bed 4 nights per week or more can expect a one-third reduction in their wet nights with a single intranasal dose of desmopressin before bedtime. Relapse rates upon cessation of treatment are very high, while side effects appear to be few. However, there are increasing reports of hyponatremic seizures. There is a group of patients in which bed-wetting appears to be the result of insufficient nocturnal secretion of vasopressin.. Desmopressin is a simple-to-use and effective drug for the treatment of nocturnal enuresis; it has opened important new avenues of inquiry, but more information is required about its long-term effectiveness and unwanted side effects.

Topics: Child; Deamino Arginine Vasopressin; Enuresis; Humans; Recurrence; Vasopressins

Conclusive evidence of a polyuric etiology from a failure of vasopressin elevation led to a new pharmacologic approach to the treatment of childhood nocturnal enuresis. Desmopressin acetate, a vasopressin analogue, has been used successfully since 1978 to treat this condition. Desmopressin's efficacy at doses of 5 to 40 micrograms has been demonstrated in Europe and the United States. Similarly, its safety has been established, and it is a first-line choice for physicians worldwide.

Topics: Child; Clinical Trials as Topic; Deamino Arginine Vasopressin; Enuresis; Europe; Female; Humans; Male; Safety; United States; Vasopressins

Topics: Adult; Child; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Prevalence; Scandinavian and Nordic Countries; Sleep; Urodynamics; Vasopressins

The role played by antidiuretic hormone in enuresis remains controversial. As a symptomatic treatment, desmopressin (DDAVP) has already proved to be a useful addition to the measures applied against this condition.

Topics: Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Double-Blind Method; Enuresis; Humans; Polyuria; Vasopressins

Arginine vasopressin preparations have been used in the treatment of diabetes insipidus for many years. Compared with older antidiuretic agents, the synthetic analog desmopressin is more potent, longer acting and easier to use. It is available for intravenous, subcutaneous and intranasal administration. Desmopressin may be useful in the treatment of hemostatic disorders such as von Willebrand's disease and hemophilia A. It has also been used for nocturnal enuresis. The vasopressor effects of arginine vasopressin preparations have been exploited for use as a temporizing measure in controlling acute gastrointestinal bleeding. Side effects such as hyponatremia and water intoxication are uncommon when these drugs are used with proper precautions.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Enuresis; Gastrointestinal Hemorrhage; Hemorrhagic Disorders; Humans; Vasopressins

Primary nocturnal enuresis (PNE) is the most common type of nocturnal enuresis in children, but its etiology remains unclear. Recent studies indicated the differences in urinary electrolytes in enuretic children, and stressed the existence of a renal tubular maturation defect. In this study, 30 children (aged 6-12 years) with PNE were investigated in comparison with 18 healthy controls. We evaluated plasma antidiuretic hormone, electrolytes, 24-h urine volume, osmolarity, and urinary electrolytes. Unlike other studies, we firstly assessed the plasma and urinary adrenomedullin (AM) and total nitrite levels, a stable product of nitric oxide (NO), and investigated their relationship with urinary electrolytes. The plasma AM and total nitrite levels were significantly lower than controls. Urine volume (24-h) and potassium excretion were higher than in controls. However, 24-h urinary osmolarity and excretion of AM were significantly lower than in controls. Our results indicate that there may be a problem in renal regulation of potassium in children with PNE. Although decreased levels of AM and total nitrite may be a compensatory response to abnormal potassium and water excretion, further investigations are required to exclude whether the renal synthesis of AM and NO are also deficient in these children.

Topics: Adrenomedullin; Algorithms; Child; Enuresis; Female; Humans; Male; Nitrites; Osmolar Concentration; Peptides; Potassium; Sodium; Urodynamics; Vasopressins

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.

Topics: Aquaporin 2; Aquaporin 6; Aquaporins; Calcium, Dietary; Child; Creatinine; Diet; Diuresis; Enuresis; Humans; Receptors, Calcium-Sensing; Receptors, Cell Surface; Treatment Outcome; Vasopressins

To test the hypotheses that vasopressin deficiency or hypercalciuria are important in polyuric and non-polyuric bedwetting, as nocturnal polyuria is a pathogenetic factor in enuresis responsive to antidiuretic therapy with desmopressin.. Vasopressin deficiency has been implicated as a cause of nocturnal polyuria, but measurements of vasopressin in plasma have given contradictory results, because the hormone is released in pulses. Urinary levels reflect the secretion over longer periods. Hypercalciuria has also been proposed as a pathogenetic factor. Twenty-eight enuretic children who responded to desmopressin therapy with or without added anticholinergic agents (diuresis-dependent enuresis, DE), 15 children with therapy-resistant enuresis (not diuresis-dependent, NDE) and 51 continent controls were assessed. Urinary vasopressin, calcium and osmolality were measured in the morning after a 12-h thirst provocation. Urine production was recorded for 2 days.. Because most data were not normally distributed, the values are expressed as the median (range). There were no differences in urine osmolality; i.e. con-trols 919 (636-1232), DE 849 (462-1149), NDE 968 (664-1191) mOsml/kg); vasopressin, controls 34 (8-983), DE 26 (9-295), NDE 50 (9-116) pmol/L; or calcium excretion (expressed as the calcium/creatinine ratio), controls 0.16 (0.01-0.71), DE 0.14 (0.04-0.67), and NDE 0.23 (0.03-0.69). The DE group produced more urine, at 18.4 (9.2-52.5) mL/kg/day, than the other groups, i.e. control 12.7 (8.3-42.8) and NDE 12.1 (6.3-36.8) mL/kg/day (P = 0.008).. All enuretic children with nocturnal polyuria do not have vasopressin deficiency. The urinary calcium excretion does not differ between enuretic and dry children.

Topics: Adolescent; Calcium; Child; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Infant; Male; Renal Agents; Vasopressins

Home recordings were used to study the effect of alarm treatment, over a period of 6 weeks, in children with monosymptomatic nocturnal enuresis. Vasopressin day/night ratios were shown to be a good indicator of alarm treatment success. Serial measurement of plasma vasopressin levels is, however, unsuitable for use in the clinic, as extensive analyses would have to be performed to obtain the necessary results. Use of an alarm increased nocturnal bladder capacity, but had no effect on daytime bladder capacity, sleep patterns, vasopressin secretion, nocturnal urine output or pelvic floor activity. In addition, the results of the study suggest that an alarm treatment period of 2 months would lead to more successful results than the 6 weeks used in the study.

Topics: Behavior Therapy; Child; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Monitoring, Physiologic; Renal Agents; Treatment Outcome; Urinary Bladder; Vasopressins

Twenty-three patients (5 to 15 years of age) with primary nocturnal enuresis were treated with desmopressin (DDAVP) according to a four-step protocol with weekly reductions of daily doses (1 to 0.25 microgram/kg body weight) thus including aspects of behavior-oriented "bladder retention training". The rate of wet nights was significantly reduced while patients were on medication (p < 0.02), but the sample as a whole returned to baseline levels after medication was stopped. Six subjects (26%) were non-responders. A variety of psychological and psychosocial single factors did not significantly affect the outcome. However, a subgroup of seven patients assessed as "psychologically non-distressed" revealed better results both on medication (p < 0.02; reduction 73%) and off medication (p > or = 0.05; reduction 39%) compared to a "distressed" subgroup (N = 16). Both groups showed significant changes in wet nights over the treatment course (p < 0.02 and p > or = 0.002, respectively). There was no clear-cut relationship between laboratory data (urine volume, osmolality, vasopressin) and outcome in wet nights. Data did not suggest a subgroup of patients with particularly low nocturnal vasopressin (AVP) secretion and, thus, high rates of wet nights. Our results corroborated the finding that DDAVP is an effective substance in reducing wet nights in patients with primary nocturnal enuresis. However, with respect to major reductions and long-term results (off medication), these preliminary findings suggest that "psychological distress" seems to be a very important confounding outcome variable. Thus, careful consideration and assessment of psychological and psychosocial aspects of distress are recommended. Eventually, a combination of DDAVP treatment with counseling and/or psychotherapy may significantly improve results for the majority of patients and families.

Topics: Adolescent; Analysis of Variance; Chi-Square Distribution; Child; Child, Preschool; Clinical Protocols; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Longitudinal Studies; Male; Renal Agents; Stress, Psychological; Treatment Outcome; Vasopressins

Forty-five children aged 6-14 years with primary nocturnal enuresis were randomised to determine whether desmopressin is more effective than amitriptyline and whether the combination of amitriptyline/desmopressin is more effective than amitriptyline or desmopressin alone. Amitriptyline dosage was 25 mg for children 6-10 years and 50 mg for children aged 10-14 years. Desmopressin (20 micrograms) was given in the same dosage for all age groups. After a run-in period of 2 weeks, children were treated for 16 weeks and then observed for 12 weeks. In the amitriptyline group mean wet nights per week decreased from 5.8 +/- 0.9 to 3.3 +/- 1.9 (P < 0.0005); in the desmopressin group mean wet nights per week decreased from 6.0 +/- 0.9 to 4.7 +/- 1.7 (P < 0.02); in the amitriptyline/desmopressin group mean wet nights per week decreased from 6.3 +/- 0.9 to 3.3 +/- 2.5 (P < 0.0006). When comparing the groups, amitriptyline/desmopressin and amitriptyline were statistically more effective than desmopressin in week 6 (P < 0.009), week 8 (P < 0.03) and week 10 (P < 0.04). No significant side effects occurred. At this dose amitriptyline was more effective than desmopressin and the combination of desmopressin and amitriptyline did not confer any additional benefit.

Topics: Adolescent; Amitriptyline; Antidepressive Agents, Tricyclic; Child; Double-Blind Method; Drug Therapy, Combination; Enuresis; Female; Humans; Male; Renal Agents; Vasopressins

Topics: Adolescent; Adrenergic Uptake Inhibitors; Adult; Antidepressive Agents, Tricyclic; Circadian Rhythm; Deamino Arginine Vasopressin; Enuresis; Humans; Imipramine; Polyuria; Renal Agents; Treatment Outcome; Urination; Vasopressins

.This study was designed to investigate the curative effect of traditional Chinese medicine Zhiyi decoction combined with acupuncture in the treatment of enuresis and its influence on serum ADH and inflammatory factors. A total of 84 enuresis patients treated were selected as cases from September 2014 to January 2017, randomly divided into study and control group with 42 cases each. The control group was treated with traditional Chinese medicine Zhiyi decoction while the study group was treated with traditional Chinese medicine Zhiyi decoction combined with acupuncture. The clinical efficacy and levels of serum ADH, serum inflammatory factors (TNF-α and IL-6) were compared between two groups before and after treatment. In study group, there were 34 cases cured and 5 cases were improved. Total effective rate was 92.9% and recurrence rate was 4%. In control group, there were 23 and 7 cases cured and improved respectively. Total effective rate was 71.4% and recurrence rate was 14.3%. The total efficiency of study group was significantly higher than that of control group (P<0.05), and the recurrence rate was significantly lower than control group (P<0.05). After treatment, there was no significant change in ADH level of study group at 10am and 11pm (P>0.05). In control group, the level of ADH at 11pm before treatment was lower than that after treatment (P<0.05) and the level of ADH at 10am before treatment was not significantly different from that after treatment (P>0.05). The levels of serum TNF-α and IL-6 in study group and control group decreased at 10am and 11pm after treatment (P<0.05) There was no significant difference in serum TNF-α and IL-6 levels between study group and control group before treatment (P>0.05). Compared with simple acupuncture, traditional Chinese medicine Zhiyi decoction combined with acupuncture of children had more exact effect, changed enuresis symptoms effectively.

Topics: Acupuncture Points; Acupuncture Therapy; Adolescent; Child; Cytokines; Drugs, Chinese Herbal; Enuresis; Female; Humans; Interleukin-6; Male; Medicine, Chinese Traditional; Treatment Outcome; Tumor Necrosis Factor-alpha; Vasopressins

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.. 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.. : 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.. 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.

Topics: Adolescent; Child; Enuresis; Female; Humans; Male; Osmolar Concentration; Polyuria; Potassium; Sodium; Vasopressins

Topics: Academies and Institutes; Antidepressive Agents, Tricyclic; Child; Cholinergic Antagonists; Contraindications; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Renal Agents; Sleep Arousal Disorders; South Africa; Urinary Bladder; Vasopressins

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.. 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.. 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.. 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.

Topics: Adolescent; Adrenocorticotropic Hormone; Calcium; Child; Circadian Rhythm; Creatinine; Deamino Arginine Vasopressin; Diagnosis, Differential; Electrolytes; Enuresis; Female; Humans; Male; Polyuria; Vasopressins

To assess the role of integrated nocturnal antidiuretic hormone (ADH) secretion in children with enuresis, and possible modifications induced by treatment with imipramine.. The morning plasma ADH and nocturnal urinary ADH integrated concentrations were measured in 18 consecutive enuretic children (patients) and 21 age- and sex-matched controls admitted for minor treatment. Diurnal and nocturnal urine production, and plasma and urinary osmolality were also determined; lumbosacral radiography and uroflowmetry were undertaken in the patients. The assessments were repeated after 14 days of treatment with imipramine hydrochloride (orally, 20 mg/night).. Half the patients had occult spinal malformations but the uroflowmetry results were all within the normal range. The median (95% confidence interval, CI) urinary ADH integrated concentrations were markedly lower in patients, at 29.7 (22.1-37.3) vs 63.0 (35.1-90.8) pg/mL/h (P = 0.03) than in controls. Plasma ADH levels were significantly increased by imipramine (0.64 to 1.47 pg/mL, 95% CI, 0.40-0.89 vs -0.26-3.2; P < 0.001), as were nocturnal urinary ADH integrated concentrations, at 29.7 (22.1-37.3) vs 59.0 (37.3-80.6) pg/mL/h (P < 0.001), and morning plasma osmolality decreased, from 298.5 (294.5-302.5) to 294.9 (292.4-297.3) mosmol/kg (P = 0.003), as was the 24-h fluid intake, from 983 (721-1245) to 666 (435-897) mL (P = 0.004).. We conclude that enuretic children have a lower nocturnal ADH excretion; imipramine restores nocturnal ADH excretion, increases morning plasma ADH levels, and causes consistent changes in other biochemical variables.

Topics: Administration, Oral; Child; Enuresis; Female; Humans; Imipramine; Lumbar Vertebrae; Male; Osmolar Concentration; Treatment Outcome; Urination; Vasopressins; Water-Electrolyte Balance

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.

Topics: Child; Circadian Rhythm; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Osmolar Concentration; Polyuria; Renal Agents; Time Factors; Urination Disorders; Urine; Vasopressins

To determine the effect of long-term desmopressin therapy in enuretic patients on the levels of antidiuretic hormone (ADH) during and after the end of therapy.. The study comprised 25 outpatients (18 boys and seven girls) aged 8-12 years at the start of therapy and 12-16 years at the end. The morning (08.00 hours) plasma ADH level was determined before treatment (T0) with desmopressin and 2 years after (T1) ending the therapy. Seven of the 25 patients evaluated had monosymptomatic (simple enuresis, SE) and 18 had other symptoms (complex enuresis, CE).. In the patients with SE, the mean (SD) duration of therapy was 305 (183) days and they were reevaluated 2.5 (0.67) years later. Of 18 patients with CE, eight were treated only with desmopressin for 204 (117) days. In 10 with an incomplete response after 30 days with only desmopressin, oxybutynin (5 mg twice daily) was added; the duration of their therapy was 255 (152) days and they were re-evaluated 3.9 (0.6) years later. The mean (SD) ADH level in those with SE and CE was 2.14 (0.93) ng/L and 2.53 (1.16) ng/L), respectively, both significantly lower (P < 0.001) than in controls, at 5.1 (1.6) ng/L. On re-evaluation at T1, there was a significant (P < 0.001) increase in ADH levels over those at T0 in both groups, at 5.2 (0.8) and 5.3 (1.9) ng/L, respectively.. These results seem to confirm the role played by ADH in the pathophysiology of enuresis.

Topics: Adolescent; Child; Cholinergic Antagonists; Deamino Arginine Vasopressin; Drug Therapy, Combination; Enuresis; Female; Humans; Long-Term Care; Male; Mandelic Acids; Renal Agents; Vasopressins

Diurnal changes of extracellular body water in enuretic (n = 8) and healthy children (n = 8) and plasma antidiuretic hormone level were examined in enuretic patients, using bioelectrical impedance analysis and radioimmunoassay. In enuretic children day/night values of extracellular space were 25.81% (10.90 l) vs 25.00% (10.52 l), with a night reduction of 3.13% (daytime 100%) (0.38 l). In controls the same parameters were 24.92% (11.88 l) vs 24.82% (11.80 l), the difference is 0.44% (0.08 l). In patients plasma antidiuretic hormone values were 2.96 pM/ml during the day and 2.70 pM/ml in the night. Results show, that in enuretic children there is a nocturnal reduction in extracellular water (p < 0.01), and the physiological nocturnal rise in antidiuretic hormone secretion in absent.

Topics: Adolescent; Child; Enuresis; Extracellular Space; Female; Humans; Male; Renal Agents; Vasopressins

Plasma arginine vasopressin (AVP) levels, urinary flow and urine osmolality were investigated in a group of adolescents (20 boys and 5 girls), aged 11-21 y, with severe monosymptomatic nocturnal enuresis and a control group of healthy adolescents (16M and 4F) with similar age- and sex-distribution. Half of the control group was investigated twice, with an interval of 6 months. AVP samples were taken every fourth hour in all adolescents and half of the control group were also investigated every second hour to achieve more samples during controlled sleep. After the study the enuretic group were put on long-term oral desmopressin (DDAVP). The difference between day and night values of AVP was significant for both groups, but there was no difference in the day/night ratios of plasma-AVP. All the adolescents produced less urine while asleep, but the controls produced significantly more urine than the enuretics during day. The controls also had a significantly larger nocturnal elevation of urine osmolality than the enuretics, thus a tendency towards polyuria was found. We could not find any significant difference between responders to DDAVP treatment and non-responders in any of the parameters studied. AVP is secreted in a pulsatile fashion and with point hormone samples taken every fourth or second hour we were unable to find any difference in the diurnal AVP secretion between enuretics and normal controls.

Topics: Adolescent; Adult; Analysis of Variance; Case-Control Studies; Child; Circadian Rhythm; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Kidney Concentrating Ability; Longitudinal Studies; Male; Renal Agents; Urine; Vasopressins

Topics: Aquaporin 2; Aquaporin 6; Aquaporins; Circadian Rhythm; Enuresis; Humans; Ion Channels; Vasopressins

The clinical and urodynamic approach to enuretic children over a period of more than 20 years has allowed the authors to develop a multifactorial pathophysiological concept of this disorder. The main factors involved are psychological, familial, genetic, vesical, due to bladder immaturity, hormonal, due to a defect of nocturnal ADH secretion, hygiene and dietary habits, etc. The sleep factor is predominant in the majority of cases. Although nocturnal enuresis is apparently isolated in many cases, it is often associated with a state of bladder immaturity, sometimes latent during the day, but occurring at night with episodes of detrusor hyperactivity, occurring during various phases of sleep. In practice, the recognition, in children, of these factors, some of which require specific treatments, implies a management combining several of these therapeutic modalities.

Topics: Child; Circadian Rhythm; Combined Modality Therapy; Enuresis; Family Health; Feeding Behavior; Humans; Hygiene; Muscle Contraction; Muscle, Smooth; Renal Agents; Sleep; Urinary Bladder; Urinary Bladder Diseases; Urination; Urodynamics; Vasopressins

The study entered 30 children with nocturnal enuresis and 20 healthy controls aged 6-15 years. The enuretic children had a higher night diuresis and free water reabsorption; there was an increase in nocturnal excretion of sodium, calcium and magnesium ions. Before going to bed the patients received diclofenac-sodium. Inhibition of cyclooxygenase and decrease of prostaglandin production led to normalization of diuresis and natriuresis, elimination of nocturnal enuresis episodes. The evidence has been obtained that nocturnal enuresis is accompanied by an increased production of autocoids in the thick ascending Henle loop and, as a result, of an increase in saluresis and diuresis. It is suggested that there is a form of nocturnal diuresis which depends on a local hyperproduction of autocoids. The problem of autocoids role in the internal medicine is discussed.

Topics: Adolescent; Body Water; Calcium; Child; Creatinine; Cyclooxygenase Inhibitors; Diclofenac; Dinoprostone; Diuresis; Eicosanoids; Enuresis; Humans; Loop of Henle; Magnesium; Nephrons; Sodium; Vasopressins

Based on several intervention programmes, a strategy for the treatment of nocturnal enuresis has recently been developed by an expert committee in the Netherlands. It consists of three parts. First, two structured interviews are given: one to differentiate between enuresis and incontinence and one to detect associated problems such as diurnal enuresis, constipation or behavioural problems. Secondly, a medical examination is made, confined to the inspection of the external genitalia and lower back, palpation of the abdomen and urine examination. Thirdly, the following guidelines for treatment at different age levels are applied: up to the age of 6 years no intervention is needed; between the ages of 6 and 8 years, lifting out of bed and/or the calendar method; between the ages of 8 and 12 years, enuresis alarm (if not successful, medication with desmopressin is prescribed for a restricted period of time), and ambulatory dry-bed training in a group setting may follow; over 13 years of age, clinical dry-bed training according to the Messer/Azrin method is advised. According to the expert committee, these guidelines offer sufficient possibilities to deal with the problem of nocturnal enuresis.

Topics: Adolescent; Child; Child, Preschool; Circadian Rhythm; Deamino Arginine Vasopressin; Enuresis; Guidelines as Topic; Humans; Netherlands; Treatment Outcome; Vasopressins

Nocturnal enuresis is characterized by nocturnal urine volumes exceeding bladder capacity and by inability to wake up to the stimulus of a full bladder. Desmopressin (DDAVP) is believed to be efficient in treating nocturnal enuresis by reducing nocturnal urine production. However, clinical observations indicate an additional mode of action since the drug appears to modify sleep architecture, apparently improving the patient's ability to awaken to the stimulus of a full bladder. Because of this, a possible arousing effect of DDAVP was studied.. The tentative ability of DDAVP and the endogenous hormone vasopressin (AVP) to produce locomotor stimulation in resting rats after both intracerebroventricular and subcutaneous administration was used as an animal model of arousal. In addition brain monoamine biochemistry was analyzed.. The intracerebroventricular injection of AVP (0.1 and 1 microgram.) and the intracerebroventricular (0.1, 1, 10 and 100 microgram.) and subcutaneous (90 and 180 microgram.) injections of DDAVP were both associated with a significant increase in the locomotor activity of the animals compared with controls. The biochemical analysis of cerebral monoamines indicated that DDAVP lowers brain dopamine levels after both types of administration.. These results suggest that DDAVP exerts a stimulatory effect in the CNS, which is also observed after peripheral administration. There are also indications for an increase in central dopamine turnover which could explain the registered increase in locomotor activity.

Topics: Animals; Brain; Deamino Arginine Vasopressin; Dopamine; Enuresis; Injections, Intraventricular; Injections, Subcutaneous; Motor Activity; Rats; Rats, Sprague-Dawley; Renal Agents; Vasopressins

Treatment of primary nocturnal enuresis using DDAVP is based upon the hypothesis that antidiuretic hormone (ADH) secretion is insufficient at night. The known efficacy of the treatment on the one hand, and persisting doubts about its theoretical basis on the other, formed the background of the present study. Ten children (mean age 10.5 years) with primary nocturnal enuresis were compared with a corresponding control group of eight patients. Diurnal and nocturnal urine production, ADH secretion, and plasma osmolality were determined. No differences between the two groups were found for urine production, ADH levels during day and night, or plasma osmolality. However, in order to regulate plasma osmolality the enuretic children required a markedly greater output of ADH: 2.87 (95% confidence interval 0.091 to 40.35) pg/ml/mmol/kg v 0.56 (0.08 to 1.03) in the controls (p < 0.01). The results are consistent with the established fact that ADH secretion is a function of plasma osmolality, and they contradict the hypothesis that urine production is increased at night in enuretics because of lower ADH secretion. The findings do not solve the uncertainties in the pathogenesis of enuresis but they suggest there might be a difference between enuretic children and controls at the ADH receptor level.

Topics: Child; Circadian Rhythm; Deamino Arginine Vasopressin; Diuresis; Enuresis; Female; Humans; Male; Osmolar Concentration; Prospective Studies; Single-Blind Method; Vasopressins

Although nocturnal enuresis was first described centuries ago, there is still a lot unknown about its pathophysiology. The functional bladder capacities, diurnal vasopressin levels, urine osmolalities and urine output of enuretic and normal children were compared. We have concluded that enuretics have normal bladder capacities insufficient for increased nocturnal urine volumes because of loss of diurnal variation in serum vasopressin levels and related decrease in urinary osmolalities.

Topics: Child; Enuresis; Female; Humans; Male; Osmolar Concentration; Urinary Bladder; Vasopressins

Topics: Child; Child, Preschool; DNA; Enuresis; Humans; Infant; Neurophysins; Polymerase Chain Reaction; Vasopressins

Topics: Central Nervous System; Circadian Rhythm; Enuresis; Humans; Kidney; Monitoring, Physiologic; Pressure; Urinary Bladder; Urinary Incontinence; Urination Disorders; Vasopressins

Topics: Central Nervous System; Child; Child, Preschool; Circadian Rhythm; Deamino Arginine Vasopressin; Enuresis; Humans; Polyuria; Renal Agents; Treatment Failure; Urination; Urodynamics; Vasopressins

Plasma and urinary levels of vasopressin were measured by radioimmunoassay in 18 children with primary nocturnal enuresis and 20 age and sex matched controls. All subjects followed a protocol whereby all urine were collected and divided up into daytime (8 a.m.-8 pm) and night-time (8 p.m. - 8 a.m.) samples. Urine osmolality and urinary vasopressin levels were measured and, following an overnight observation period, the following morning (8 a.m.) plasma vasopressin was measured. Plasma vasopressin was significantly lower in the enuretic group (2.86 +/- 0.44 pg/ml) compared to the control group (3.64 +/- 1.35 pg/ml) (p = 0.011). Total urinary vasopressin excretion over 24 hours was lower in the enuretic group but the difference was not significant. These results support the hypothesis that one of the factors responsible for nocturnal enuresis in children may be due to a reduced nocturnal secretion of vasopressin. This may explain why the vasopressin substitution therapy is able to successfully abolish nocturnal enuresis symptoms.

Topics: Adolescent; Child; Circadian Rhythm; Enuresis; Female; Humans; Male; Osmolar Concentration; Vasopressins

Topics: Cues; Enuresis; Humans; Vasopressins

Topics: Behavior Therapy; Child; Cues; Enuresis; Humans; Vasopressins

Topics: Child; Deamino Arginine Vasopressin; Drug Approval; Enuresis; Humans; United States; United States Food and Drug Administration; Vasopressins

This prospective self-controlled study was designed to evaluate the safety and efficacy of Desmopressin (DDAVP) in the treatment of childhood primary nocturnal enuresis (PNE) and the diurnal variation of ADH secretion and urine excretion/concentration in these children. Twenty-three children (15M,8F), aged 5-16 years, who wet their beds at least 3 nights per week were enrolled in the study. After a four-week observation period, they were hospitalized for one day to monitor intake, output, renal sonography, plasma ADH, urine and serum osmolality. Intranasal DDAVP treatment at a dose of 15-30 micrograms at bedtime was started with a 4-week titration period followed by a 3 to 6-month full dose treatment period. Subsequently the dose was tapered off for one to two months, and the patients were followed for at least two months to observe any recurrence. The results showed no diurnal difference of ADH level in these children (p > 0.05); serum osmolality decreased slightly during sleep (p < 0.01); urine production decreased, and urine osmolality increased, during sleep. Seventeen children (81%) responded with a more than 50% reduction in frequency of enuresis: 11 were excellent responders, 6 were partial responders, while 4 failed. After completion of therapy, four (19%) remained dry and were considered cured; the rest had much less frequent recurrence. There were no subjective complaints other than mild local discomfort; laboratory test results remained normal. It was concluded that intranasal DDAVP is a safe and effective treatment for PNE which usually works promptly. Given the spontaneous annual remission rate of 14%, the cure rate of 19% in this study was not satisfactory.

Topics: Administration, Intranasal; Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Drug Evaluation; Enuresis; Female; Humans; Male; Osmolar Concentration; Prospective Studies; Remission Induction; Vasopressins

Topics: Advertising; Child, Preschool; Crying; Drug Information Services; Enuresis; Humans; Infant; Vasopressins

Topics: Child; Deamino Arginine Vasopressin; Enuresis; Humans; Vasopressins

Eight patients with monosymptomatic nocturnal enuresis (age 11-24 years) were investigated prior to and after 24 weeks of desmopressin treatment in order to evaluate the impact on the endogenous vasopressin secretion and urinary output. No effect on plasma vasopressin, diurnal urinary volume, and urinary osmolality were found after this long-term treatment. Overall no changes in either body weight, blood pressure, or hematological variables were demonstrated. This supports previous findings that the treatment appears to be well tolerated and free of side effects in longer term.

Topics: Adolescent; Circadian Rhythm; Deamino Arginine Vasopressin; Enuresis; Female; Follow-Up Studies; Humans; Male; Time Factors; Urine; Vasopressins

Topics: Administration, Intranasal; Adolescent; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Vasopressins

Topics: Enuresis; Humans; Vasopressins

In 8 adult patients with monosymptomatic nocturnal enuresis (age 18-44 years) we twice investigated the circadian rhythm of plasma vasopressin, plasma atrial natriuretic peptide, serum osmolality, serum electrolytes as well as urinary excretion in relation to urodynamic variables. Seven of the patients showed a lack of diurnal rhythmicity in plasma vasopressin at both diurnal studies with no night-time increase. The nocturnal urinary volumes exceeded the bladder capacities with an average of 155%. This was mainly caused by a large excretion of poorly concentrated urine during the first hours of sleep. Although a slight nocturnal peak in plasma atrial natriuretic peptide was found no clear pathophysiological role could be determined for this peptide. It is concluded that the previously established vasopressin production abnormality in juvenile enuresis seems to persist in adult enuretics.

Topics: Adolescent; Adult; Analysis of Variance; Atrial Natriuretic Factor; Body Water; Circadian Rhythm; Electrolytes; Enuresis; Female; Humans; Kidney Tubules; Male; Osmolar Concentration; Urination; Vasopressins

Topics: Child; Circadian Rhythm; Enuresis; Humans; Vasopressins

Topics: Adolescent; Child; Child, Preschool; Enuresis; Humans; Vasopressins

Topics: Administration, Intranasal; Adolescent; Child; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Vasopressins

Topics: Adult; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Enuresis; Humans; Kidney; Kidney Concentrating Ability; Vasopressins

Topics: 17-Hydroxycorticosteroids; Adolescent; Child; Circadian Rhythm; Enuresis; Humans; Potassium; Sodium; Urine; Vasopressins

Topics: Child; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Dilatation; Enuresis; Humans; Hydronephrosis; Polyuria; Surgical Procedures, Operative; Urinary Bladder Neck Obstruction; Urography; Vasopressins

Topics: Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Vasopressins