Abnormal diurnal rhythm of plasma vasopressin and urinary output in patients with enuresis

Rittig, Søren; Knudsen, Ulla Breth; Nørgaard, Jens Peter; Pedersen, E. B.; Djurhuus, Jens Christian

doi:10.1152/ajprenal.1989.256.4.f664

Cited by 241 publications

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“…Relative vasopressin deficiency during the night was demonstrated almost 20 years ago 11 and confirmed in a subset of MNE cases. 4,12 Nocturnal polyuria is present in about 2 of 3 enuretic patients, and it has been related to nocturnal vasopressin deficiency. 12,13 The MNE population has been divided into polyuric and nonpolyuric with the latter considered detrusor-dependent with small functional bladder capacity 1,6,14 or minor bladder dysfunction, which is common in daytime symptomatic enuretic patients.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Nocturnal polyuria has been demonstrated frequently in MNE 3 and has been related to nocturnal vasopressin deficiency. 4 Desmopressin administration has been proposed and widely adopted for MNE treatment, 5 and enuretic patients have been differentiated into responders (65%) and nonresponders (35%). 6 Urinary electrolyte excretion has recently been studied in MNE.…”

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confidence: 99%

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Sodium Fraction Excretion Rate in Nocturnal Enuresis Correlates With Nocturnal Polyuria and Osmolality

et al. 2004

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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 Ͻ0.001). In group 1 nocturnal FE Na correlated with nocturnal diuresis (Pearson correlation p ϭ 0.003, r ϭ ϩ0.175), while daytime FE Na and nocturnal FE Na correlated with diurnal diuresis (Pearson correlation p ϭ 0.001, r ϭ ϩ0.225 and Pearson correlation p ϭ 0.001, r ϭ ϩ0.209, respectively). In group 2 nocturnal FE Na did not correlate with diuresis (Pearson correlation p ϭ 0.103, r ϭ ϩ0.128) but correlated with vasopressin values (Pearson correlation p ϭ 0.042, r ϭ Ϫ0.205). Urine osmolality was reduced in 140 children (31.9%) and correlated with nocturnal diuresis (Pearson correlation p ϭ 0.003, r ϭ Ϫ0.321). 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. KEY WORDS: enuresis, polyuria, vasopressins, electrolytes, desmopressin Pathogenesis of monosymptomatic nocturnal enuresis (MNE) is still debated as different etiopathogenetic hypotheses have been proposed, accepted or rejected during the last century....

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Sodium Fraction Excretion Rate in Nocturnal Enuresis Correlates With Nocturnal Polyuria and Osmolality

et al. 2004

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“…Following the observation by Rittig et al, that children with enuresis showed a significantly lower nocturnal increase in arginine-vasopressine (AVP) [3], it was subsequently used for an indication primarily seen in children; enuresis nocturna. Until now, DDAVP is the only drug therapy with evidence level 1, grade A recommendation, for the indication of monosymptomatic nocturnal enuresis (MNE) [4].…”

Section: Introductionmentioning

confidence: 99%

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children

et al. 2016

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Introduction: Desmopressin is used for nocturnal enuresis treatment in children. In this study, we investigated the pharmacokinetics of two formulations: a tablet and a lyophilisate, in both fasted and fed children.Methods: Previously published data from two studies (22 children aged 6 to 16 yr and 25 children aged 6 to 13 yr) were analyzed using population pharmacokinetic modeling. A 1-compartment model with first order absorption was fitted to the data. Covariates were selected using a forward selection procedure. The final model was evaluated, and sensitivity analysis was performed to improve future sampling designs. Simulations were subsequently performed to further explore the relative bioavailability of both formulations and the food effect.Results: The final model described the desmopressin plasma concentrations adequately.Formulation and fed state were included as covariates on the relative bioavailability. The lyophilisate was on average 32.1 % more available than the tablet, and fasted children exhibited an average increase in relative bioavailability of 101%, compared to fed children. Body weight was included as a covariate on distribution volume, using a power function with exponent 0.402.Simulations suggest both the formulation and the food effect are clinically relevant. Conclusions:Bioequivalence data of two formulations of the same drug in adults, cannot be readily extrapolated to children. This is the first study in children suggesting that the two desmopressin formulations in children are not bioequivalent at the currently approved dose levels.Furthermore, the effect of food intake was found to be clinically relevant. Sampling times for a future study were suggested. This sampling design should result in more informative data and consequently generate a more robust model. Key points Population pharmacokinetic modeling was applied to pediatric desmopressin PK data and used to extract more information out of existing pediatric drug data, generate new information and improve the collection of future information. In this study it was found that the established bioequivalence of desmopressin in adults might be different in the pediatric population. A profound food effect was also quantified. In order to make solid conclusions regarding desmopressin efficacy in children, PK and PD data should be gathered simultaneously in a well-designed study, for which some design suggestions are presented in this paper. Abbreviations

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“…Despite a maturation rate of 15% per year, 0.5% of all cases remain in adulthood, with serious effects on self-esteem (6). Among various hypotheses on the pathophysiology of PNE, it has been proposed that patients with PNE have insufficient nightly increase of AVP, leading to the production of large amounts of dilute urine, thereby surpassing the bladder capacity (7). Successful application of a synthetic analogue of AVP, desmopressin (dDAVP), a V2R agonist, seemed to confirm this hypothesis.…”

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confidence: 99%

Relief of Nocturnal Enuresis by Desmopressin Is Kidney and Vasopressin Type 2 Receptor Independent

Robben¹,

Sze²,

Knoers

et al. 2007

Journal of the American Society of Nephrology

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Primary nocturnal enuresis (PNE) is a common problem in childhood and adolescence. Although various treatments are highly effective, a common underlying hypothesis on the pathogenesis is lacking. The success of desmopressin, a synthetic analogue of the antidiuretic hormone vasopressin, has been attributed to increased renal water reabsorption that is mediated by activation of the renal vasopressin V2 receptor (V2R). However, this effect does not explain other symptoms of PNE, such as the failure to arouse upon bladder distension. This study identified a family in which one child displayed PNE and coexisting nephrogenic diabetes insipidus, as a result of a novel nonsense mutation in the V2R gene (C358X). Cell-biologic investigations revealed that V2R-C358X is retained in the endoplasmic reticulum and is unstable, which explains his nephrogenic diabetes insipidus. Consistently, extrarenal V2R-mediated responses were absent in the patient who was treated with desmopressin. Administration of desmopressin, however, changed his PNE into nocturia, because he now still voided unchanged high urinary volumes at night but woke up and went to the bathroom. Withdrawal of desmopressin was accompanied by bedwetting, whereas reintroduction again relieved the symptoms. Therefore, these data indicate that neither a functioning renal concentration system nor a functional V2R is needed for the therapeutic benefit of desmopressin in PNE. Rather, it suggests that another vasopressin receptor and other organ(s) is the target for desmopressin to relieve PNE.

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Abnormal diurnal rhythm of plasma vasopressin and urinary output in patients with enuresis

Cited by 241 publications

References 0 publications

Sodium Fraction Excretion Rate in Nocturnal Enuresis Correlates With Nocturnal Polyuria and Osmolality

Sodium Fraction Excretion Rate in Nocturnal Enuresis Correlates With Nocturnal Polyuria and Osmolality

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children

Relief of Nocturnal Enuresis by Desmopressin Is Kidney and Vasopressin Type 2 Receptor Independent

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