Effect of DDAVP on nocturnal enuresis in a patient with nephrogenic diabetes insipidus

The case of an 8 year old boy with both nocturnal enuresis and nephrogenic diabetes insipidus is presented. Diagnosis of nephrogenic diabetes insipidus was based on a typical medical history, the characteristic result of a fluid restriction test, the lack of an effect of 1-desamino-8-D-arginine (DDAVP) on both urine osmolality and plasma coagulation factors and, finally, the detection of a hemizygous missense mutation within the arginine vasopressin (AVP) receptor gene. Hydrochlorothiazide treatment and dietary measures reduced the patient''s urine volume to one third of its original volume. However, this had no effect on enuresis. The daily intranasal application of DDAVP did not further reduce urine output but dramatically decreased the frequency of bed wetting. This observation contradicts the common notion that the therapeutic effect of DDAVP in nocturnal enuresis is the result of compensation for a nocturnal AVP deficit. Rather, it points to a different mode of action of DDAVP in patients with enuresis. It is hypothesised that central AVP receptors are a target of DDAVP and that they might play an important role in the pathogenesis of nocturnal enuresis.     

Effect of DDAVP on nocturnal enuresis in a patient with nephrogenic diabetes insipidus.

The case of an 8 year old boy with both nocturnal enuresis and nephrogenic diabetes insipidus is presented. Diagnosis of nephrogenic diabetes insipidus was based on a typical medical history, the characteristic result of a fluid restriction test, the lack of an effect of 1-desamino-8-D-arginine (DDAVP) on both urine osmolality and plasma coagulation factors and, finally, the detection of a hemizygous missense mutation within the arginine vasopressin (AVP) receptor gene. Hydrochlorothiazide treatment and dietary measures reduced the patient's urine volume to one third of its original volume. However, this had no effect on enuresis. The daily intranasal application of DDAVP did not further reduce urine output but dramatically decreased the frequency of bed wetting. This observation contradicts the common notion that the therapeutic effect of DDAVP in nocturnal enuresis is the result of compensation for a nocturnal AVP deficit. Rather, it points to a different mode of action of DDAVP in patients with enuresis. It is hypothesised that central AVP receptors are a target of DDAVP and that they might play an important role in the pathogenesis of nocturnal enuresis.     

Antidiuretic hormone regulation in patients with primary nocturnal enuresis.

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.     

DDAVP in childhood nocturnal enuresis

A double-blind study of 18 children aged 6--12 years suffering from primary nocturnal enuresis without signs of underlying organic disease is reported. 20 microgram of DDAVP (desamino-D-arginine vasopressin, Minirin) was given intranasally at bedtime. The effect was prompt and satisfactory in 8 children and relatively good in another 8 children. No adverse effects were noted. DDAVP is advocated for temporary use in children with nocturnal enuresis needing immediate help.     

DDAVP IN CHILDHOOD NOCTURNAL ENURESIS

ABSTRACT. A double-blind study of 18 children aged 6–12 years suffering from primary nocturnal enuresis without signs of underlying organic disease is reported. 20 μg of DDAVP (desamino- d -arginine vasopressin, Minirin®) was given intranasally at bedtime. The effect was prompt and satisfactory in 8 children and relatively good in another 8 children. No adverse effects were noted. DDAVP is advocated for temporary use in children with nocturnal enuresis needing immediate help.     

Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD syndrome). A clinical study in two Sudanese families

Four Sudanese children with DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) are reported. They were two boys (aged 15 and 16 years) in one family and a boy and a girl (aged 16 and 6 years, respectively) in another family. Diabetes mellitus was first to appear (at 3-8 years) followed by deafness and visual failure; and the disease ended fatally in one patient (aged 20 years). In the other three, diabetes insipidus was confirmed using water deprivation test for 8 hours. The maximum urine osmolality ranged between 131-523 mOsm/kg, whereas the corresponding plasma osmolality ranged between 315-332 mOsm/kg. Slight further improvement in urine concentration was observed in 2 of the patients following the use of desmopressin (DDAVP, 20 micrograms intranasally). Intravenous pyelography, voiding cystourethrography and ultrasound revealed severe bilateral hydronephrosis, dilated ureters and distended bladder without vesicoureteral reflux in the three patients. With the high rate of consanguinity prevalent in North Africa and the Middle East, we recommend examining children who present with diabetes mellitus in this region for features of DIDMOAD syndrome.     

Diurnal plasma vasopressin and urinary output in adolescents with monosymptomatic nocturnal enuresis

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.     

Comparison of desmopressin and enuresis alarm for nocturnal enuresis.

Fifty children with primary nocturnal enuresis were randomised for a study comparing desmopressin (DDAVP) and enuresis alarm. Forty six completed the trial, 24 of whom were treated with 20 micrograms intranasal desmopressin nightly and 22 with enuresis alarm for three months. Failures were crossed over and relapses were continued on the same treatment for a further three months. The improvement rate was 70% in the group given desmopressin and 86% in the group treated with alarm; the difference was not significant. During the first week of treatment the group given desmopressin was significantly dryer, and at the end of the study 10 of these patients relapsed compared with one patient in the group given the alarm. No serious side effects were observed. This study confirms the role of conditioning treatment as preferable in long term treatment of nocturnal enuresis. When this fails or when a safe drug with rapid effect is needed, however, desmopressin is a useful alternative.     

Low-dose DDAVP in nocturnal enuresis.

A five-year experience with the vasopressin analogue desmopressin acetate (DDAVP) for nocturnal enuresis is described in 59 children. The initial starting dose of 5 micrograms at bedtime is lower than that reported in other series. Eighty-one percent of patients required 10 micrograms or less to achieve improvement or resolution of bedwetting.     

Treatment for nocturnal enuresis: The current state in Japan

Nocturnal enuresis is common problem in children with a prevalence as high as 20% among children aged 5. Though nocturnal enuresis does not directly impose imminent danger to a patient's life, children with enuresis and their parents can be psychologically suffering in day‐to‐day life, including in school activities. Therefore, it is important to provide an explanation regarding the cause of nocturnal enuresis, how to approach the disorder, the course, and the outlook leading to the planned treatment. The cause of enuresis is considered to be a mismatch between nocturnal diuresis and nocturnal bladder capacity, nocturnal polyuria due to a lack of circadian change in antidiuretic hormones, and a developmental delay in the voiding mechanisms. Therefore, patients can be classified as the type associated with a large amount of urine at night (polyuria type), the type that is associated with a functionally small bladder capacity (bladder type), the type associated with both the aforementioned (mixed type), or the type that does not fall under any of these (normal type). Based on this logic, although the International Children's Continence Society has issued the standardization document, in which the enuresis alarm and desmopressin therapy are recommended as the first line treatment, a different tack has been taken in Japan, where the therapeutic strategy is plotted depending on the type of enuresis; pharmacotherapy for enuretic children aged 6 years or older includes desmopressin acetate for polyuria type, anticholinergic agents for bladder type, and a combination of these agents for mixed type.     

Desmopressin in nocturnal enuresis.

The response of desamino-D-arginine vasopressin (DDAVP) was investigated in 32 enuretic children in a double-blind clinical study. The 15 children treated with DDAVP showed a significant reduction in the incidence of bed wetting--from 18.7 +/- 6.5 to 6.5 +/- 9.2 wet nights per 30 days. In 6 children bed wetting stopped entirely, in 6 there was a satisfactory response, and in 3 the response was marginal or there was none. When DDAVP was stopped most children reverted to their earlier bedwetting habits (15.7 +/- 8.9 nights a month). Response to DDAVP was significantly better in children aged more than 10 years (mean age for the entire group). The administration of DDAVP was not associated with any appreciable change in morning urine osmolalities. No adverse effects were noted. It is concluded that DDAVP is effective in nocturnal enuresis, particularly in older children. It is suggested that the cessation of bed wetting may, in part, reflect functional properties of DDAVP rather than antidiuresis.     

Desmopressin in the management of nocturnal enuresis in children: a double-blind study.

Desmopressin (1-desamino-[8-D-Arg]-vasopressin) (DDAVP) was given by nose drops to 22 children with persistent nocturnal enuresis (mean age, 6.6 +/- 2.9 years; range, 4 to 12 years) the evening before sleep. With saline alone as placebo and with comparison to enuretic frequency before the onset of the trial, fortnightly periods were compared under double-blind conditions with the children at home. Pretreatment and placebo fortnights showed wetting frequencies (nights per fortnight) of 10.6 +/- 4.9 and 11.0 +/- 4.4, respectively. The value of the fortnight during desmopressin therapy was 4.2 +/- 4.5, which was significantly different from either of the previous means (P less than .01). Of the 22 subjects, four failed to react to therapy at all. There was decreased enuretic frequency in the remaining 18, of whom 12 decreased markedly or ceased wetting. One month after the trial, seven of the respondents were dry with desmopressin therapy. There was clear evidence of a large nocturnal volume of dilute urine before treatment in six of the respondents in whom such measurements could be reliably made. These children responded to dehydration with urine concentration, however, so that the suggestion can be made that a failure to develop a normal diurnal pattern of urine volume and concentration may underly some cases of enuresis.     

The treatment of nocturnal enuresis. A comparative study between desmopressin and acupuncture used alone or in combination]

During the period from March to September 1989, 40 children suffering from primary nocturnal enuresis, aged between 5 and 14 years, were included in a study to assess the comparative therapeutical efficacy of DDAVP and acupuncture. Children were divided into four groups of 10: group A was treated with DDAVP, group B was treated with acupuncture, group C was treated with DDAVP and acupuncture and group D was treated with placebo (control). The trial design included 3 periods: observation (2 weeks), treatment (8 weeks) and follow-up (4 weeks). Nineteen children completed the study. The efficacy of treatment, which was expressed as a percentage of dry nights, was high in both the DDAVP and acupuncture groups, when used separately. The combined treatment of DDAVP and acupuncture appeared to be the most efficacious both in terms of the percentage of dry nights at the end of treatment and in relation to the stability of results, even after the end of the study. The paper gives a detailed analysis of correlations between type of treatment and urinary osmolarity.     

Hyponatremia in patients with nocturnal enuresis treated with DDAVP

Treatment of nocturnal enuresis with DDAVP is associated with a low incidence of adverse effects. The only reported serious adverse effect is seizure or altered level of consciousness due to water intoxication. We reviewed 14 articles that reported data on serum sodium in patients treated with DDAVP for nocturnal enuresis and 11 articles that reported patients who developed a seizure or altered level of consciousness during treatment with DDAVP for nocturnal enuresis. Excess fluid intake was identified as a contributing factor in 6 of the 11 case reports.     

Oxybutynin efficacy in the treatment of primary enuresis

The effectiveness of oxybutynin in the treatment of primary enuresis was evaluated in a double-blind study. A total of 30 children (25 boys, five girls), at least 6 years of age, with primary enuresis and no daytime incontinence or history of other urinary tract problems were selected at random from an enuresis clinic population. The study was explained to the families and they were told how to keep records of nocturnal bed-wetting episodes and side effects. The patients were treated with a 10 mg of oxybutynin at suppertime for 28 days. Before or after the treatment period, all children received an identical placebo for 4 weeks. Two-sided paired t tests were used to compare frequency of nocturnal enuresis. Frequency during the drug regimen did not differ significantly from that during the placebo study. There were no differences in findings between boys and girls or between children who had previously taken imipramine and those who had not. The study showed no evidence that oxybutynin is effective in treating primary enuresis.     

Central diabetes insipidus in children. V. Oral treatment with a vasopressin hormone analogue (DDAVP)

1-deamino-8-D-arginine-vasopressin, or DDAVP, a potent long acting antidiuretic analogue of AVP, is the treatment of choice in central diabetes insipidus (DI). We have studied the clinical and biological effect in 10 children with DI treated with peroral administration of DDAVP. During a dose ranging study in hospital, followed by 6 months of treatment at home, this peroral DDAVP tablet proved to be as effective as the intranasal administration of DDAVP and was preferred by the patients. Even doses as small as 12.5 micrograms, have an effect on diuresis and urinary osmolality. Therapeutic effects start at above 100 micrograms. During the dose ranging study 200 micrograms peroral DDAVP produced antidiuresis varying from 8 to 12.5 hours, in different patients. The recommended dose is 100-300 micrograms 2-3 times a day. This treatment offers an important alternative to that traditionally used and constitutes one of the first examples of a peptide conserving its biological activity after gastrointestinal transport.     

Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (DIDMOAD Syndrome): A Clinical Study in Two Sudanese Families

ABSTRACT. Four Sudanese children with DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) are reported. They were two boys (aged 15 and 16 years) in one family and a boy and a girl (aged 16 and 6 years, respectively) in another family. Diabetes mellitus was first to appear (at 3–8 years) followed by deafness and visual failure; and the disease ended fatally in one patient (aged 20 years). In the other three, diabetes insipidus was confirmed using water deprivation test for 8 hours. The maximum urine osmolality ranged between 131–523 mOsm/kg, whereas the corresponding plasma osmolality ranged between 315–332 mOsm/kg. Slight further improvement in urine concentration was observed in 2 of the patients following the use of desmopression (DDAVP, 20 μg intranasally). Intravenous pyelography, voiding cystourethrography and ultrasound revealed severe bilateral hydronephrosis, dilated ureters and distended bladder without vesicoureteral reflux in the three patients. With the high rate of consanguinity prevalent in North Africa and the Middle East, we recommend examining children who present with diabetes mellitus in this region for features of DIDMOAD syndrome.     

Evaluation of nocturnal bladder capacity and nocturnal urine volume in nocturnal enuresis

ObjectiveTo investigate the diagnostic accuracies of maximum voided volume (MVV) and first morning urine osmolality and compare these with accuracies of nocturnal bladder capacity (NBC) and nocturnal urine volume, respectively, in children with nocturnal enuresis.Materials and methodsA total of 70 children with nocturnal enuresis were assessed (mean age 7.1 ± 2.2 years). Baseline parameters were obtained by measuring MVV using a voiding diary, first morning urine osmolality on a wetting day, diaper weight by checking twice per night and first morning urine volume.ResultsThe proportions of small NBC and small MVV were 34.3% (24 cases) and 55.7% (39 cases), respectively. The proportions of low osmolality of first morning urine and nocturnal polyuria (NP) were 45.7% (32 cases) and 25.7% (18 cases), respectively. The sensitivity and specificity of small MVV for small NBC were 53.8% and 90.3%, respectively; the sensitivity and specificity of first morning urine osmolality for NP were 33.3% and 50.0%, respectively.ConclusionsThe diagnostic accuracies of MVV and urine osmolality for small NBC and NP were only modest to low.     

Treatment of nocturnal enuresis: a placebo-controlled trial with piracetam, diphenylhydantoin and psychotherapy

The study population consisted of 100 children with nocturnal enuresis (NE) aged between six and 14 years, who had been randomly selected amongst the enuretic outpatients at the Ankara S.S.K. Children's Hospital. A placebo-controlled evaluation of piracetam, diphenylhydantoin and psychotherapy was carried out. At the end of the eighth week of the study, it was discovered that the therapeutic effects observed in the patients administered piracetam did not differ from those given the placebo. Therefore, we recommend that psychotherapy in association with a placebo be the first step in the treatment of NE children.     

Social and behavioural perspectives in enuretics, former enuretics and non-enuretic controls

Social and behavioural traits in children with primary nocturnal enuresis were compared with children who had outgrown their enuresis and children who had never bed-wetted after three years of age. The study group included 14 children with primary nocturnal enuresis, 15 children who had had primary nocturnal enuresis and 15 age- and sex-matched controls. The mothers of all children were interviewed using a 32-item questionnaire. If primary nocturnal enuresis were a neurotic disease, we would have expected a higher frequency of emotional dysfunction in children with enuresis and an increase in the symptoms or symptom substitution when bed-wetting was resolved. No significant differences in emotional or behavioural traits among the three groups were found. We conclude that children with primary nocturnal enuresis were well adjusted individuals and display similar social and behavioural traits as their peers. This study lends further support to the theory that primary nocturnal enuresis is not a psychological disorder.