Fig 4 - uploaded by Kaj Anker Jørgensen
Content may be subject to copyright.
Diurnal variations in the plasma (P-) levels of atrial natriuretic peptide (ANP), aldosterone (ALDO), angiotensin II (ATII), and activated renin as well as in P-Na and P-urea concentrations for all groups of participants . *P 0.05. **P 0.01.
Source publication
The transition from day to night is associated with a pronounced decline in diuresis with reductions in the amount of excreted water, electrolytes, and other end products of our metabolism. Failure to do so leads to a large urine output at night, a condition known as nocturnal polyuria, encountered in a large proportion of children with nocturnal e...
Contexts in source publication
Context 1
... in plasma. P-Na concentrations varied slightly but significantly and with no significant differences between the groups at any point (Fig. 4). Potassium levels consistently followed a circadian rhythm with the lowest val- ues around midnight. Plasma osmolality was also consistently higher at the very start of the experimental period, reaching the lowest levels at 1200 and ...
Context 2
... urea (P-urea) measurements peaked around 1600 for both controls and nonpolyurics, decreasing significantly there- after (Fig. 4). In polyurics, P-urea had a tendency to remain at higher levels during both the evening hours and the initial hours of the night, and the difference between the polyurics and controls reached statistical significance at both 2000 and ...
Context 3
... measurements. Figure 4 shows the diurnal varia- tions of the hormones studied. Apart from a consistent noctur- nal peak at 2400, the profile of plasma ANP (P-ANP) was stable throughout the 24-h experimental period. ...
Context 4
... the hormone markedly declined toward the evening and the first hours of the night to continuously rise thereafter until the early morning Fig. 3. Circadian variation in excretion and fractional excretion of sodium (ENa and FENa, respectively) and urea (EUr and FEUr, respectively) among the different groups of participants. **P 0.01. ***P 0.001. (Fig. 4). Nonpolyurics had higher P-Aldo levels than the other groups at 2000 and ...
Similar publications
Hypercalciuria may present with dysuria, urinary incontinence and nocturnal enuresis (NE). To determine the frequency of hypercalciuria in NE patients and normally continent children, we studied 122 consecutive pre- school children with NE referred to our nephrology clinic during two years, from September 2007 to August 2009. We measured the 24- ho...
Nocturia may be a multifactorial condition and should be regarded as a syndrome rather than a diagnosis, with many factors contributing to the clinical presentation. The effects of sleep deprivation can have a severely detrimental impact on the quality of life and productivity of the working age population, with considerable economic implications....
In 1998, the endogenous ligand for the human orphan APJ receptor, ie, apelin, was isolated from bovine stomach extracts. Apelin naturally occurs in the brain and plasma as 13 (pE13F) and 17 amino acid (K17F) fragments derived from 77 amino acid precursor, preproapelin. Apelin and its receptor are highly expressed in magnocellular vasopressinergic n...
Sex hormones have a pronounced effect on arginine vasopressin (AVP), and therefore on the diurnal water homeostasis. Low and high levels of plasma-estradiol as seen in the follicular phase of the menstrual cycle may therefore alter the diurnal regulation of urine production. Furthermore the structural resemblance of oxytocin to vasopressin has led...
Aims To estimate the relationship between pharmacokinetics and antidiuretic effect of desmopressin. Methods An investigator-blind, randomized, parallel group study with five dose-groups and one placebo, each consisting of 12 healthy, over-hydrated, non-smoking male subjects 18-55 years of age were infused intravenously over two hours with Placebo,...
Citations
... 8,9 Refractory enuresis coincides with several pathogenetic characteristics and comorbidities, which are the expertise of different pediatric subdisciplines: urology (lower urinary tract symptoms [LUTS], thickened bladder wall, pre-existing uropathy, neurogenic and non-neurogenic bladder), nephrology (suboptimal maximal renal concentrating capacity in nocturnal polyuria, chronic kidney disease [CKD], abnormal circadian rhythms of glomerular filtration rate [GFR], water and solute handling), hypertension (absent nocturnal dipping), overall abnormal circadian rhythms of sleep, hormones (vasopressin, renin-angiotensin-aldosterone system [RAAS], prostaglandins, blood pressure), independent or associated with disrupted sleep (periodic limb movement syndrome [PLMS], obstructive sleep apnea syndrome [OSAS]), constipation. [10][11][12][13][14][15][16][17][18][19] To tackle this complexity in pathogenesis in refractory enuresis patients, the concept of multidisciplinary teams was developed in pediatric tertiary enuresis centers. 20 Most of the characteristics are organic and likely hereditary, implying that the cure of the symptom enuresis does not correlate with normalizing the underlying pathogenetic factors. ...
... This has been clearly documented in pediatric enuresis. 13,16,34 Although there are many similarities to results in the elderly nocturia group, there are also many differences. Little is known about the AYA population, but most likely, they should be treated according to the enuresis guidelines, even for their nocturia, rather than the nocturia guidelines in adults. ...
Background
Nocturnal enuresis is generally considered a children's condition, yet it may persist 1%–2% in adolescence and early adulthood. Refractory patients often demand follow‐up by multidisciplinary teams, which is only restricted to some of the expert tertiary centers. However, there are no standardized transition programs/guidelines when follow‐up must be passed from pediatric to adult healthcare providers.
Aim, Materials & Methods
To investigate this issue, we conducted a literature search on enuresis transition, which resulted in no articles. We, therefore, proceeded in a rescue search strategy: we explored papers on transition programs of conditions that may be related and/or complicated by enuresis, nocturia, or other urinary symptoms (chronic diseases, CKD, bladder dysfunction, kidney transplant, neurogenic bladder).
Results
These programs emphasize the need for a multidisciplinary approach, a transition coordinator, and the importance of patient and parent participation, practices that could be adopted in enuresis. The lack of continuity in enuresis follow‐up was highlighted when we investigated who was conducting research and publishing on enuresis and nocturia. Pediatric disciplines (50%) are mostly involved in children's studies, and urologists in the adult ones (37%).
Discussion
We propose a stepwise approach for the transition of children with enuresis from pediatric to adult care, depending on the clinical subtype: from refractory patients who demand more complex, multidisciplinary care and would benefit from a transition coordinator up to children/young adults cured of enuresis but who persist in having or present lower urinary tract symptoms (LUTS)/nocturia later on. In any case, the transition process should be initiated early at the age of 12–14 years, with adequate information to the patient and parents regarding relapses or LUTS/nocturia occurrence and of the future treating general practitioner on the enuresis characteristics and comorbidities of the patient.
... It is well described that at least some children with nocturnal polyuria have increased sodium excretion during wet nights, and that nocturnal polyuria is not only explained by AVP alterations [45,46], which is in line with our findings of increased but not significant sodium excretion. This is supported by the observation that only one child experienced full response to DDAVP treatment after urine collection. ...
Background:
Nocturnal enuresis (NE) is a common disease with multiple pathogenic mechanisms. This study aimed to compare levels of metabolites and proteins between wet and dry nights in urine samples from children with monosymptomatic NE (MNE).
Methods:
Ten boys with MNE and nocturnal polyuria (age: 7.6 ± 1.3 years) collected their total nighttime urine production during a wet and a dry night. Untargeted metabolomics and proteomics were performed on the urine samples by liquid chromatography coupled with high-mass accuracy tandem mass spectrometry (LC-MS/MS).
Results:
On wet nights, we found reduced urine osmolality (P = 0.025) and increased excretion of urinary potassium and sodium by a factor of, respectively, 2.1 (P = 0.038) and 1.9 (P = 0.19) compared with dry nights. LC-MS identified 59 metabolites and 84 proteins with significantly different levels between wet and dry nights (fold change (FC) < 0.67 or > 1.5, P < 0.05). Some compounds were validated by different methodologies. During wet nights, levels of compounds related to oxidative stress and blood pressure, including adrenalin, were increased. We found reduced levels of aquaporin-2 on wet nights. The FCs in the 59 metabolites were positively correlated to the FCs in the same metabolites identified in urine samples obtained during the evening preceding wet and dry nights.
Conclusions:
Oxidative stress, which in the literature has been associated with nocturia and disturbances in sleep, might be increased during wet nights in children with MNE. We further found evidence of increased sympathetic activity. The mechanisms related to having wet nights in children with MNE seem complex, and both free water and solute handling appear to be important. A higher resolution version of the Graphical abstract is available as Supplementary information.
... Its side effects include dry mouth, dry eyes, constipation, urinary tract infection, hypertension, headache, blurred vision, and drowsiness [9]. Further, evidence suggests overproduction of prostaglandin E2 during the night in some children with enuresis [10]. Therefore, cyclooxygenase inhibitors such as indomethacin, which have been demonstrated to possess antidiuretic properties, have been used for treating patients with enuresis [11]. ...
Objectives:
To compare the efficacy of desmopressin plus tolterodine (D+T) with desmopressin plus indomethacin (D+I) for treating enuresis in children.
Design:
Open-label randomized controlled trial.
Setting:
Bandar Abbas Children's Hospital, a tertiary care children's hospital in Iran, from March 21, 2018, to March 21, 2019.
Participants:
40 children older than five years with monosymp-tomatic and non-monosymptomatic primary enuresis resistant to desmopressin monotherapy.
Intervention:
Patients were randomized to receive either D+T (60 µg sublingual desmopressin and 2 mg tolterodine) or D+I (60 µg sublingual desmopressin and 50 mg indomethacin) every night before bedtime for five months.
Outcome:
Reduction in the frequency of enuresis was evaluated at one, three, and five months, and response to treatment at five months. Drug reactions and complications were also noted.
Results:
After adjustment for age, consistent incontinence from toilet training, and non-monosymptomatic enuresis, D+T was significantly more efficacious than D+I in nocturnal enuresis reduction at 1, 3, and 5 months showing a large effect. At 5 months, complete response to treatment was only observed with D+T, while treatment failure was significantly higher with D+I. None of the patients in either group developed cutaneous drug reactions or central nervous system symptoms.
Conclusion:
Desmopressin plus tolterodine appears to be superior to desmopressin plus indomethacin for treating pediatric enuresis resistant to desmopressin.
... Monosymptomatic nocturnal enuresis (MNE) is defined as isolated urinary incontinence during sleep without symptoms during the day and without lower urinary tract symptoms or bladder dysfunction after the age of 5 years, 1 affecting 7%-10% of children. 2 It often leads to psychosocial problems because of its burden and stigmatism. 3 Besides education and simple behavioral interventions, the 2 main treatment options for the management of MNE are enuresis alarm and arginine vasopressin (AVP) analog desmopressin. ...
Objective:
One of the main medical treatment options for monosymptomatic nocturnal enuresis (MNE) is the vasopressin analogue desmopressin. But not all children respond to desmopressin treatment, and no reliable treatment predictor has yet been established. We hypothesize that plasma copeptin, a surrogate marker for vasopressin, can be used to predict treatment response to desmopressin in children with monosymptomatic nocturnal enuresis.
Design/methods:
In this prospective observational study, we included 28 children with MNE. At baseline, we assessed number of wet nights, morning and evening plasma copeptin and plasma sodium and started treatment with desmopressin (120mcg/day). Desmopressin was increased to 240mcg/day if clinically necessary. The primary endpoint was reduction in number of wet nights, following 12 weeks of treatment with desmopressin using plasma copeptin ratio (evening/morning copeptin) at baseline.
Results:
18 children responded to desmopressin treatment at 12 weeks, while 9 did not. A copeptin ratio cut-off of 1.34 (sensitivity 55.56%, specificity 94.12%, AUC 70.6%, p = 0.07) was best at predicting treatment response, with a lower ratio indicating a better treatment response. In contrast, neither number of wet nights at baseline (p = 0.15), nor serum sodium (p = 0.11) alone or in combination with plasma copeptin improved outcome prediction.
Conclusion:
Our results indicate that of our investigated parameters plasma copeptin ratio is the best predictor for treatment response in children with MNE. Plasma copeptin ratio could thus be useful to identify children with the highest benefit of desmopressin treatment and improve individualized treatment of monosymptomatic nocturnal enuresis.
... 3 In our study, enuretic children and control group were compared in terms of renin and aldosterone levels but no significant difference was found. Kamperis et al. 15 compared ANP, angiotensin-2, aldosterone and renin levels and, they determined no difference between enuretic children and the control group which is similar to the findings of our study. However, in the same study, a significant increase was determined in the prostaglandin E-2 (PGE2) level of patients with nocturnal polyuria and it was suggested that renal prostaglandins were the key molecule in the etiopathogenesis of enuresis. ...
Background:
Monosymptomatic nocturnal enuresis (MNE) is defined as involuntary nighttime urination of children over five years of age without any congenital or acquired defect in the central nervous system. Many factors, mainly nocturnal polyuria, sleep disorders, decreased bladder capacity, and bladder dysfunctions play a role in the etiology of MNE.
Methods:
Eighty-three children diagnosed with MNE were included in the study. Complete blood cell count, blood biochemistry, renin, and aldosterone levels of all children were obtained. Twenty-four-hour urine samples were collected separately daytime and nighttime and urinary electrolytes were evaluated. Also, 24-hour ambulatory blood pressure monitoring (ABPM) was performed for each patient. The results were evaluated by comparing both enuretic children vs. control group and enuretic children with polyuria vs. without polyuria.
Results:
When we compared the enuretic children and the control group in terms of urinary electrolytes, the fractional excretion of sodium (FENa) and fractional excretion of potassium (FEK) values of the enuretic group were higher than the control. The evaluation of the 24-hour ABPM findings revealed no significant difference in terms of the mean arterial pressure (MAP) and diastolic blood pressure (DBP) during the daytime and nighttime measurements. The daytime systolic blood pressure (SBP), however, was significantly lower in the enuretic group. When enuretic children with and without polyuria and the control group were compared, the nighttime, FENa, FEK, as well as nighttime urinary excretion of calcium and protein were significantly higher in enuretic children with polyuria. No difference was detected on the MAP, SBP, or DBP values.
Conclusions:
In conclusion, the nighttime urinary solute excretion of enuretic children was found to be higher and this condition may especially be associated with pathogenesis of nighttime polyuria. In enuretic children, nighttime blood pressure changes were not influential in the etiopathogenesis in all patient groups and multiple mechanisms may play a role in the pathogenesis of enuresis.
... www.nature.com/scientificreports/ responses to the standard treatment or experience a relapse after stopping treatment, particularly for those with NMNE 1,9 . This reflects beyond the three-system model, there are other factors involved in enuresis pathogenesis. ...
Nocturnal enuresis (NE) is a common problem among 10% school-aged children. The etiologies underlying childhood NE is complex and not fully understood nowadays. Nevertheless, increasing evidence suggests a potential link between neurobehavioral disorders and enuresis in children. In this study, we aimed to explore novel metabolomic insights into the pathophysiology of NE and also, its association with pediatric psychiatric problems. Urine collected from 41 bedwetting children and 27 healthy control children was analyzed by using ¹ H-nuclear magnetic resonance spectroscopy from August 2017 to December 2018. At regular follow-up, there were 14 children with refractory NE having a diagnosis of attention deficient hyperactivity disorder (ADHD) or anxiety. Eventually, we identified eight significantly differential urinary metabolites and particularly increased urinary excretion of betaine, creatine and guanidinoacetate linked to glycine, serine and threonine metabolism were associated with a comorbidity of neurobehavioral disorders in refractory bedwetting children. Notably, based on physiological functions of betaine acting as a renal osmolyte and methyl group donor, we speculated its potential role in modulation of renal and/or central circadian clock systems, becoming a useful urinary metabolic marker in diagnosis of treatment-resistant NE in children affected by these two disorders.
... Besides, previous studies have demonstrated that the excessive production of nocturnal urine and the development of nocturnal enuresis in children is probably attributable to the pathological presence of abnormally elevated plasma levels of vasopressin. [15][16][17] It has also been reported that some children might suffer from bladder overactivity. Nevertheless, it has also been reported that these patients usually present with other daytime clinical symptoms related to the bladder such as frequency, incontinence and urgency. ...
Nocturnal enuresis or night time incontinence is a common condition that usually affects children and can be associated with significant psychological effects on the affected child if left untreated. It can be defined as night time wetting of the bed that usually occurs in children that are ≥5 years old. In this literature review, the aim was to discuss the etiology and management of nocturnal enuresis and the impact of the condition on the different age groups. Management of the underlying comorbidities, taking care of the overactive bladder and dealing with the potential psychological conditions might be the main key factors to nocturnal enuresis. Many pharmacological and non-pharmacological approaches have been proposed for these patients. However, the success rates of applying behavioral management approaches have been reported to be the highest as compared to other approaches. Early interventions should be applied for children that have multiple risk factors or with parents that once suffered from the condition as genetics were reported in the literature to have a significant role in the development of nocturnal enuresis. Pharmacological therapies have also been reported as effective modalities in resistant cases and desmopressin was reported to achieve a 100% success rate if used with alarm therapy. However, clinicians should care for the potential adverse events when approaching the pharmacological modalities.
... The condition affects 7% to 10% of all 7-year-olds and 0.5% to 2% of young adults [1][2][3]. NE is a multifactorial disease, characterized by the production of an excessive amount of urine at night, termed nocturnal polyuria (NP), and it is the cause of bedwetting in a large number of children [4,5]. NP can be either the result of the inadequate secretion of nocturnal arginine vasopressin (AVP) or secondary to osmotic diuresis, natriuresis, hypercalciuria, or other renal factors [5][6][7]. ...
... NE is a multifactorial disease, characterized by the production of an excessive amount of urine at night, termed nocturnal polyuria (NP), and it is the cause of bedwetting in a large number of children [4,5]. NP can be either the result of the inadequate secretion of nocturnal arginine vasopressin (AVP) or secondary to osmotic diuresis, natriuresis, hypercalciuria, or other renal factors [5][6][7]. ...
Objectives: This pilot study was conducted to test the protocol of a randomized controlled trial evaluating whether rapid maxillary expansion (RME) can relieve nocturnal enuresis (NE) and improve breathing in children, after ruling out a placebo effect, and investigating whether the effects of RME and NE are related to the morphology of the upper airway. Methods: Seventy 6–15-year-old patients with NE were assessed for eligibility (e.g., constricted maxilla). Enrolled subjects were randomized to immediate treatment with RME (Group 1) or to have the same treatment (RME) delayed for at least six weeks (Group 2). Outcomes comprised the number of wet nights per week, the nocturnal urine production, and the scores of a pediatric sleep questionnaire at baseline, after active treatment (Group 1) or delayed treatment (Group 2), and after 3 months’ retention. Cone beam computed tomographies were taken at baseline and after retention. Results: Six patients were randomized: three in each group. In four of six patients, the number of wet nights per week decreased. Moreover, in responders, nocturnal urine production was reduced following RME. Conclusions: This pilot study suggested that RME might reduce the severity of NE and showed that the protocol of this randomized controlled clinical trial was appropriate.
... But an aberrant AVP circadian rhythm cannot explain nocturnal polyuria in all children. Since these initial studies on water balance and AVP, a number of other factors have been implicated in the etiology of nocturnal polyuria such as changes in renal sodium handling leading to natriuresis [8], excess calcium excretion known to impair the renal concentrating mechanisms [9], hemodynamic changes and sleep disruption, all impacting the renal solute and water excretion [10e12]. ...
... Although it can be difficult to differentiate between the effect of circadian variations in physiological processes and sleep per se on blood pressure regulation, there is little doubt that sleep attenuates the nocturnal dipping in blood pressure. NE patients have been shown to share higher BP levels during sleep compared to controls [47,48] but others could not confirm these findings [8,49,50]. This may be due to phenotypic variability on enuresis patients. ...
Nocturnal enuresis (NE) is a common condition affecting 5–10% of all 7-year-old children. NE pathophysiology relies on three main factors, abnormal bladder function, excess urine production during sleep and the inability to awaken to the signals of a full bladder. The aim of this review is to evaluate the connection between sleep and its structure and the pathophysiology of NE.
NE often occurs early at night and primarily in sleep stage 2 and “deep sleep”. Although sleep stage distribution seems similar between NE and healthy children recent studies indicate differences in sleep microstructure. Several lines of research support the common notion among parents that children with NE are difficult to awaken. Moreover, children with NE and nocturnal polyuria differ in terms of hemodynamics and possibly autonomic activation at night compared to healthy controls and the hypothesis has formed that these changes are attributable to different sleep characteristics. In support of this hypothesis, children with NE often suffer sleep disordered breathing, as well as disturbed sleep due to awakenings and arousals. Periodic limb movements (PLM) have been seen in children with refractory enuresis but the clinical significance remains unclear.
... The pathophysiology of primary MNE (PMNE) is complex and so far it has not yet been fully clarified. An altered circadian profile of antidiuretic hormone, arousal failure and delayed urinary bladder maturation are the best studied pathophysiological factors (8 Kamperis et al. documented that polyuric patients with MNE refractory to desmopressin treatment excrete larger amounts of sodium and urea at night compared with healthy controls and nonpolyurics MNE patients despite a normal the circadian rhythm of sodium-regulating hormones such as atrial natriuretic peptide, angiotensin II, aldosterone, and renin levels but may be secondary to augmented urinary prostaglandin E2 (PGE2) excretion (9). Some authors found idiopathic hypercalciuria (IH) to be more common in children with PMNE than in children without nocturnal enuresis and for this reason they assume that IH could be one of the contributing pathophysiologic factor to PMNE (10,11,12). ...
Introduction: The prevalence of idiopathic hypercalciuria (IH) in healthy pediatric population ranges from 3.0% to 7.0%. There is insufficient data about IH in children with mono-symptomatic enuresis. The aim of this study was to examine calcium excretion in urine (UCa) in patients with primary mono-symptomatic nocturnal enuresis (PMNE). Methods: In patients with PMNE, aged 5 to 17 years, IH was determined in 24-h urine and from second morning spot urine. The completeness of the 24-h urine collections was estimated via measuring 24h-urine creatinine excretion (UCr) of 0.1–0.2 mmol/kg/24h. Results: Sixty patients with PMNE, 32 males and 28 girls, median age of 9 years were enrolled in the study. Only 41.7% patients successfully completed 24 h urine collection. IH, defined as 24-h UCa >0.1 mmol/kg body weight, was diagnosed in 12% of the patients, while when defined as UCa/UCr >0.8 mmol/mmol in children 5-7 years and >0.6 mmol/mmol in those>7 years, IH was 8.3% and 6.7% from 24h- urine and spot urine, respectively. Conclusion: Children and adolescents with PMNE are in risk of hypercalciuria. Therefore, it is useful to examine 24 hours of urine calcium excretion in these patients.
