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Fardous J, Ara A, Hossain MI, Labony A, Afrin T, Ashraf R, Uddin R, Jesmin H, Alam MK, Amin MA, Khan AH, Khan ZH. Serum Antidiuretic Hormone Level in Nocturnal Enuretic School Children in a Tertiary Care Hospital in Bangladesh: A Cross-Sectional Study. Health Sci Rep 2025; 8:e70406. [PMID: 39872909 PMCID: PMC11770247 DOI: 10.1002/hsr2.70406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 01/08/2025] [Accepted: 01/13/2025] [Indexed: 01/30/2025] Open
Abstract
Background and Aims Primary nocturnal enuresis (PNE) is a common pediatric condition characterized by involuntary nighttime bed wetting. Primary monosymptomatic nocturnal enuresis (PMNE) is associated with altered antidiuretic hormone (ADH) secretion and lacks lower urinary tract symptoms. This study aimed to compare serum ADH levels between children with PMNE and a comparison group to explore its potential role in the pathophysiology of PMNE. Methods This cross-sectional study included 40 children aged 6-15 years with PMNE and 40 age-matched children without enuresis (comparison group) attending the Pediatric Nephrology Outpatient Department at the National Institute of Kidney Diseases and Urology (NIKDU) from January 2022 to July 2023. Blood samples and other clinical information along with laboratory investigation are done to ensure inclusion and exclusion criteria. Fasting serum ADH level, a competitive immunoassay was done with the Arg- Vasopressin ELISA kit. Relevant clinical and demographic data were analyzed using Student's t-test for continuous variables and Chi-square/Fisher's exact tests for categorical variables. Results The mean age of participants was 8.82 ± 2.71 years in the PMNE group and 9.01 ± 2.54 years in the comparison group (p = 0.760). There was no significant association between sex and PMNE (p = 0.370). Children with PMNE exhibited significantly lower serum ADH levels compared to the comparison group (p < 0.05). Additionally, children with more frequent enuretic episodes demonstrated a trend of lower ADH levels (p < 0.05). Conclusion This study provides evidence of a significant association between decreased diurnal serum ADH levels and PNE in children. These findings contribute to a better understanding of the pathophysiology of PNE and suggest potential avenues for novel treatment strategies, emphasizing the importance of evaluating ADH levels in PNE management.
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Affiliation(s)
- Jannatul Fardous
- National Institute of Kidney Diseases & Urology (NIKDU)DhakaBangladesh
| | - Anjuman Ara
- National Institute of Kidney Diseases & Urology (NIKDU)DhakaBangladesh
| | - Md. Iqbal Hossain
- National Institute of Kidney Diseases & Urology (NIKDU)DhakaBangladesh
| | - Asma Labony
- National Institute of Kidney Diseases & Urology (NIKDU)DhakaBangladesh
| | - Tanjila Afrin
- National Institute of Kidney Diseases & Urology (NIKDU)DhakaBangladesh
| | - Rezwana Ashraf
- National Institute of Kidney Diseases & Urology (NIKDU)DhakaBangladesh
| | - Reaz Uddin
- National Institute of Kidney Diseases & Urology (NIKDU)DhakaBangladesh
| | - Habiba Jesmin
- National Institute of Kidney Diseases & Urology (NIKDU)DhakaBangladesh
| | - Md. Kabir Alam
- National Institute of Kidney Diseases & Urology (NIKDU)DhakaBangladesh
| | | | | | - Zahid Hasan Khan
- International Centre for Diarrheal Disease ResearchBangladesh (icddr,b)DhakaBangladesh
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Karamaria S, Dossche L, Dhondt K, Everaert K, Van Herzeele C, Walle JV, Raes A. Effect of desmopressin on water and solute circadian rhythms in treatment-naïve children with monosymptomatic enuresis and nocturnal polyuria. Pediatr Nephrol 2024:10.1007/s00467-024-06579-z. [PMID: 39531076 DOI: 10.1007/s00467-024-06579-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 10/08/2024] [Accepted: 10/15/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Enuresis has a complex pathophysiology involving nocturnal polyuria, reduced bladder capacity at nighttime, and impaired arousability. Desmopressin has long been used as a treatment. However, approximately 30% of children do not fully respond to it, suggesting the involvement of other factors. Solute handling and osmotic excretion have been studied in refractory patients. Nevertheless, data on the effect of desmopressin on these factors are sparse. METHODS We conducted a post hoc analysis of the SLEEP study. We analyzed the circadian rhythm of solute and water excretion before and after desmopressin in 30 children with monosymptomatic enuresis and nocturnal diuresis > 100% of expected bladder capacity by means of a 24-h urine concentration profile (four daytime and four nighttime urine portions at equivalent time intervals). RESULTS Under desmopressin, nocturnal diuresis (rate) and Na/creatinine ratio were significantly lower compared to day values (p = 0.009, p = 0.021, respectively). Osmolality, Na/creatinine, and osmotic excretion showed a significant day vs. night variance only after desmopressin. Nighttime osmotic and sodium excretion were significantly lower (p = 0.004, p = 0.019, respectively) under treatment, indicating the impact of desmopressin on kidney sodium handling. During desmopressin treatment, nocturnal diuresis (rate) showed strong positive correlation with nighttime Na/creatinine (r = 0.436, p < 0.05) and very strongly with nighttime osmotic excretion (r = 0.875, p < 0.0001). However, no correlation was observed with osmolality under desmopressin treatment. CONCLUSIONS The anti-enuretic and antidiuretic effects of desmopressin therapy are not only related to urinary concentration and nocturnal diuresis but also to the amelioration of circadian rhythms of sodium and solute handling.
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Affiliation(s)
- Sevasti Karamaria
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
| | - Lien Dossche
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium
| | - Karlien Dhondt
- Department of Child & Adolescent Psychiatry, Pediatric Sleep Center, Ghent University Hospital, Ghent, Belgium
| | - Karel Everaert
- Department of Urology, Ghent University Hospital, Ghent, Belgium
| | | | - Johan Vande Walle
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Ann Raes
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium
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Chang TL, Kuo HC. Nocturia, nocturnal polyuria, and nocturnal enuresis in adults: What we know and what we do not know. Tzu Chi Med J 2024; 36:370-376. [PMID: 39421492 PMCID: PMC11483088 DOI: 10.4103/tcmj.tcmj_53_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 03/29/2024] [Accepted: 04/13/2024] [Indexed: 10/19/2024] Open
Abstract
Nocturia is defined as the nocturnal frequency of one or more voiding episodes per night. It increases with aging and has an impact on sleep quality and the risks of falling and mortality. Nocturia disorder involves nighttime frequency, nocturnal polyuria, and nocturnal enuresis. In older adults with nocturia disorder, multiple factors could contribute to nocturia severity and characteristics, including poor sleep quality, lower urinary tract dysfunction, and excessive fluid output. Several nonurological medical diseases have been found to result in nocturia, such as hypertension, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease, metabolic syndrome, and diabetes. Urological and medical assessments should be performed to diagnose nocturia disorder. A frequency volume chart to evaluate the nocturnal polyuria index, functional bladder capacity, and urodynamic study can reveal the presence of nocturnal polyuria and lower urinary tract dysfunction. Treatment should be based on multiple nocturia etiologies, and a combination of multiple therapies for individual pathophysiology will achieve a better treatment outcome.
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Affiliation(s)
- Tien-Lin Chang
- Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Hann-Chorng Kuo
- Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
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Karamaria S, Dhondt K, Everaert K, Mauel R, Nørgaard JP, Raes A, Van Herzeele C, Verbakel I, Walle JV. First uninterrupted sleep period in children and adolescents with nocturnal enuresis: Added value in diagnosis and follow-up during therapy. Neurourol Urodyn 2024; 43:1147-1154. [PMID: 37929315 DOI: 10.1002/nau.25322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 10/22/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND The first uninterrupted sleep period (FUSP, time up to the first episode of enuresis/nocturia after falling asleep) is a frequently investigated parameter in adults with nocturia, as it correlates with quality of life. However, it has not been included in pediatric enuresis studies. AIM Investigate FUSP, circadian renal water and sodium handling, as well as sleep quality before and after desmopressin therapy in enuresis. MATERIALS AND METHODS We conducted a post hoc analysis of a prospective study in 30 treatment-naïve children with enuresis who underwent a video-polysomnography and a 24-h urine concentration profile before and after 6 months of desmopressin therapy. We analyzed FUSP, periodic limb movements in sleep (PLMS), and arousal indexes and their correlations with the urinary parameters. RESULTS Sixteen children with a mean age of 10.9 ± 3.1 years had full registrations and were included in this subanalysis. After therapy, FUSP was significantly longer (p < 0.001), and the PLMS index was lower (p = 0.023). Significant differences in the circadian rhythm of diuresis (night/day diuresis, p = 0.041), nocturnal urinary osmolality (p = 0.009), and creatinine (p = 0.001) were found, demonstrating the increase of urinary concentration overnight by desmopressin, as well as a significant antidiuretic effect (diuresis [p = 0.013] and diuresis rate (p = 0.008). There was no correlation between the difference of FUSP, PLMS index, and urinary parameters. Nevertheless, despite this study being underpowered, there are indications of a correlation between nocturnal diuresis and diuresis rate. RESULTS Our results support the need for further research regarding FUSP in children with enuresis, in accordance with nocturia studies in adults, as this parameter could be valuable in the follow-up and evaluation of therapeutic strategies for enuresis.
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Affiliation(s)
- Sevasti Karamaria
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Karlien Dhondt
- Department of Child and Adolescent Psychiatry, Pediatric Sleep Center, Ghent University Hospital, Ghent, Belgium
| | - Karel Everaert
- Department of Urology, Ghent University Hospital, Ghent, Belgium
| | - Reiner Mauel
- Department of Pediatric Intensive Care, Brussels University Hospital, Brussels, Belgium
| | | | - Ann Raes
- Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium
| | | | - Irina Verbakel
- Department of Urology, Ghent University Hospital, Ghent, Belgium
| | - Johan Vande Walle
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium
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Karamaria S, Dossche L, Delens V, Degraeuwe E, Raes A, Mauel R, Vande Walle C, Everaert K, Vande Walle J. Circadian rhythm of water and solute excretion in nocturnal enuresis. Pediatr Nephrol 2023; 38:771-779. [PMID: 35748940 DOI: 10.1007/s00467-022-05645-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 05/11/2022] [Accepted: 05/27/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND Nocturnal polyuria (NP) due to a suppressed vasopressin circadian rhythm is a well-documented pathogenetic mechanism in enuresis, mainly studied in monosymptomatic enuresis. A substantial percentage of patients do not respond to desmopressin. This suggests that NP may not only be related to vasopressin, but that other kidney components play a role. Solute handling and osmotic excretion have been investigated in the past, especially in refractory patients. Nevertheless, data in treatment-naïve populations with information on timing overnight are sparse. This study aims to investigate the diuresis and solute excretion in treatment-naïve patients with or without NP, with emphasis on circadian rhythms. METHODS Retrospective analysis of 403 treatment-naïve children 5-18 years with severe enuresis (> 8 nights/2 weeks). Circadian rhythms were evaluated by a 24-h urine collection in 8 timed portions (4 day, 4 nighttime) at in-home settings. Urine volume, osmolality, and creatinine were measured. Patients were subdivided into three groups according to nocturnal diuresis (ND) and Expected Bladder Capacity (EBCage) ratio: (a) < 100%, (b) 100-129%, (c) > 130%. RESULTS All groups maintained circadian rhythm for diuresis and diuresis rates. Patients with higher ND (100-129% and > 130% EBCage) had higher daytime volumes and less pronounced circadian rhythm. In the ND group > 130% EBCage, the ND rate was higher during the first night collection and osmotic excretion was significantly higher overnight. CONCLUSIONS Overall 24-h fluid intake (reflected by 24-h diuresis) and nutritional intake (24-h osmotic excretion) might play a role in enuresis. Increased diuresis rate early in the night can be important in some patients, whereas the total night volume can be important in others. A higher resolution version of the Graphical abstract is available as Supplementary Information.
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Affiliation(s)
- Sevasti Karamaria
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium
| | - Lien Dossche
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium
| | - Vincent Delens
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Eva Degraeuwe
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Ann Raes
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium
| | - Reiner Mauel
- Department of Pediatric Intensive Care, Brussels University Hospital, Brussels, Belgium
| | | | - Karel Everaert
- Department of Urology, Ghent University Hospital, Ghent, Belgium
| | - Johan Vande Walle
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
- Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium.
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Tsuji S, Kaneko K. Management of treatment-resistant nocturnal enuresis. Pediatr Int 2023; 65:e15573. [PMID: 37428825 DOI: 10.1111/ped.15573] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 05/11/2023] [Accepted: 05/12/2023] [Indexed: 07/12/2023]
Abstract
Nocturnal enuresis is defined as intermittent urinary incontinence during sleep in children 5 years of age and older, occurring at least once a month for at least 3 months. In Japan, pediatricians who do not specialize in nocturnal enuresis have become more proactive in treating the condition since 2016, when the guidelines for treating it were revised for the first time in 12 years. For monosymptomatic nocturnal enuresis, the first step is lifestyle guidance, with a focus on the restriction of fluid intake at night; however, if lifestyle guidance does not decrease the frequency of nocturnal enuresis, aggressive treatment should be added. The first choice of aggressive treatment is oral desmopressin, an antidiuretic hormone preparation, or alarm therapy. However, there remain patients whose wet nights do not decrease with oral desmopressin or alarm therapy. In such cases, it is necessary to reconfirm the method of desmopressin administration and check for factors that may decrease the efficacy of desmopressin. If alarm therapy does not increase the number of dry nights, it is possible that the patient is fundamentally unsuitable for alarm therapy. If dry nights do not increase with oral desmopressin or alarm therapy, the next treatment strategy should be considered immediately to keep the patient motivated for treatment.
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Affiliation(s)
- Shoji Tsuji
- Department of Pediatrics, Kansai Medical University, Osaka, Japan
| | - Kazunari Kaneko
- Department of Pediatrics, Kansai Medical University, Osaka, Japan
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Kuzmin IV. Primary enuresis in adults: pathogenesis, clinical course and modern approaches to treatment: A review. CONSILIUM MEDICUM 2022. [DOI: 10.26442/20751753.2022.10.201947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The review article presents current data on the epidemiology, classification, pathogenesis, risk factors, diagnosis, and features of the clinical course of primary enuresis in adults. The main methods of treatment of patients with primary enuresis are described in detail. It has been shown that in the treatment of this category of patients, the leading role is given to the use of a synthetic analogue of the antidiuretic hormone desmopressin. A detailed analysis of the pharmacological properties and clinical use of desmopressin in patients with primary enuresis is presented. The advantages of prescribing a sublingual form of desmopressin, which ensures its high efficiency and good tolerability of therapy.
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Ghogare A, Pole R, Vankar G. A clinical review of enuresis and its associated psychiatric comorbidities. ANNALS OF INDIAN PSYCHIATRY 2022. [DOI: 10.4103/aip.aip_102_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Yu MC, Wang TM, Chiou YH, Yu MK, Lin CF, Chiu CY. Urine metabolic phenotyping in children with nocturnal enuresis and comorbid neurobehavioral disorders. Sci Rep 2021; 11:16592. [PMID: 34400733 PMCID: PMC8368245 DOI: 10.1038/s41598-021-96104-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 08/03/2021] [Indexed: 12/16/2022] Open
Abstract
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 1H-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.
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Affiliation(s)
- Mei-Ching Yu
- Division of Pediatric Nephrology, Department of Pediatrics, Lin-Kou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 5, Fusing Street, Gueishan, Taoyuan, 333, Taiwan.
| | - Ta-Min Wang
- Division of Pediatric Urology, Department of Urology, Lin-Kou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yee-Hsuan Chiou
- Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Meng-Kung Yu
- Department of Pediatrics, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan
| | - Chiao-Fan Lin
- Department of Child and Adolescent Psychiatry, Lin-Kou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chih-Yung Chiu
- Division of Pediatric Pulmonology, Department of Pediatrics, Clinical Metabolomics Core Laboratory, Lin-Kou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 5, Fusing Street, Gueishan, Taoyuan, 333, Taiwan.
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Physiological rhythms are influenced by photophase wavelength in a nocturnal and a diurnal rodent species from South Africa. Physiol Behav 2021; 240:113551. [PMID: 34375624 DOI: 10.1016/j.physbeh.2021.113551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/02/2021] [Accepted: 08/04/2021] [Indexed: 11/22/2022]
Abstract
The quality and quantity of light changes significantly over the course of the day. The effect of light intensity on physiological and behavioural responses of animals has been well documented, particularly during the scotophase, but the effect of the wavelength of light, particularly during the photophase, less so. We assessed the daily responses in urine production, urinary 6-sulfatoxymelatonin (6-SMT) and glucocorticoid metabolite (uGCM) concentrations in the nocturnal Namaqua rock mouse (Micaelamys namaquensis) and diurnal four striped field mouse (Rhabdomys pumilio) under varying wavelengths of near monochromatic photophase (daytime) lighting. Animals were exposed to a short-wavelength light cycle (SWLC; ∼465-470 nm), a medium-wavelength light cycle (MWLC; ∼515-520 nm) and a long-wavelength light cycle (LWLC; ∼625-630 nm). The SWLC significantly attenuated mean daily urine production rates and the mean daily levels of urinary 6-SMT and of uGCM were inversely correlated with wavelength in both species. The presence of the SWLC greatly augmented overall daily 6-SMT levels, and simultaneously led to the highest uGCM concentrations in both species. In M. namaquensis, the urine production rate and urinary 6-SMT concentrations were significantly higher during the scotophase compared to the photophase under the SWLC and MWLC, whereas the uGCM concentrations were significantly higher during the scotophase under all WLCs. In R. pumilio, the urine production rate and uGCM were significantly higher during the scotophase of the SWLC, not the MWLC and LWLC. Our results illustrate that wavelength in the photophase plays a central role in the entrainment of rhythms in diurnal and nocturnal African rodent species.
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Gözüküçük A, Kılıç M, Çakıroğlu B. Desmopressin versus desmopressin + oxybutynin in the treatment of children with nocturnal enuresis. J Pediatr Urol 2021; 17:451.e1-451.e6. [PMID: 33931318 DOI: 10.1016/j.jpurol.2021.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/30/2021] [Accepted: 04/01/2021] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Enuresis is identified as voluntary or involuntary leakage of urine for at least three consecutive months in the daytime and/or nighttime on clothes for children older than five. Monosymptomatic nocturnal enuresis (MNE) describes nighttime wetting without daytime leakage of urine in children with no pathology in the urinary system and it is 80% more common than enuresis. Desmopressin is the most common medical treatment for MNE. The aim of this study is to retrospectively compare the effectiveness of desmopressin as monotherapy and desmopressin + oxybutynin as a combination therapy in the treatment of nocturnal enuresis. MATERIAL AND METHOD This study retrospectively evaluated 183 patients who applied to pediatrics, pediatrics surgery and urology clinics with the complaint of nocturnal enuresis and diagnosed with primary monosymptomatic nocturnal enuresis between January 2014 and December 2019. The patients were divided into two groups (91 patients) who only received desmopressin therapy (Group 1), and those (92 patients) who received desmopressin and oxybutynin combination therapy (Group 2). Response to treatment, compliance and recurrence ratios were determined in the evaluation. Complete response was accepted as 90-100% decrease in the number of nighttime wetting, partial response was accepted as 50-90% decrease in the number of nighttime wetting and those below 50% were regarded as non-response. The 1st, 3rd, and 6th months of control data of treatment effectiveness of both groups were evaluated and their responses to treatment and the side effects of drugs were examined. RESULTS The mean age 183 patients of whom 103 were male and 80 were female was 10 (6-16) year. In the first month of control of Group 1, 71.4% had a complete cure, 8.8% had a partial cure and 19.8% had no response to treatment. In the third month of control of Group 1, 74.73% gave a complete response and were cured, 5.5% gave a partial response and 19.78% had no response. In the sixth month of Group 1, 70 patients were evaluated as complete response (79.5%), and 5 patients were evaluated as partial response (5.6%). In the first month of control of Group 2, 75% gave a complete response, 10.9% gave a partial response, 14.1% had no response to treatment. In the third month of control of Group 2, 86.9% gave a complete response, 6.52% gave a partial response, and 6.52% had no response. In the sixth month of the control of Group 2, the number of patients who did not come for control and could not be reached was 2, 83 patients out of 90 patients were evaluated as complete response (92.2%), 6 patients were evaluated as partial response (6.6%). CONCLUSION Desmopressin is the only FDA approved pharmacologic treatment for nocturnal enuresis. Desmopressin reduces urine production and the anticholinergic agent allows the bladder to store more urine. Therefore, combined therapy can be recommended in the MNE treatment for specially selected cases.
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Affiliation(s)
- Ali Gözüküçük
- Department of Pediatric Surgery, Hisar Intercontinental Hospital, Dogus University, İstanbul, Turkey.
| | - Mehmet Kılıç
- Department of Pediatrics, Hisar Intercontinental Hospital, Dogus University, İstanbul, Turkey.
| | - Basri Çakıroğlu
- Department of Urology, Hisar Intercontinental Hospital, İstanbul, Turkey.
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Dossche L, Michelet R, De Bruyne P, Van Herzeele C, Gasthuys E, Rittig S, Vermeulen A, Vande Walle J. Desmopressin oral lyophilisate in young children: new insights in pharmacokinetics and pharmacodynamics. Arch Dis Child 2021; 106:597-602. [PMID: 32737054 DOI: 10.1136/archdischild-2019-318225] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 04/05/2020] [Accepted: 06/18/2020] [Indexed: 11/04/2022]
Abstract
OBJECTIVE To study the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of desmopressin (dDAVP) oral lyophilisate in children below the age of 8 years with special emphasis on age-related and size-related differences in bioavailability. DESIGN Open label, non-randomised, interventional PK and PD trial. SETTING Single-centre study. PATIENTS Children (age: 6 months to 8 years) with nocturnal polyuria, including both children with uropathy or nephropathy (glomerular filtration rate >60 mL/min/1.73 m²) and children (age: 5-8 years) with severe monosymptomatic nocturnal enuresis, who were unresponsive to treatment with 400 µg of the dDAVP tablet for at least 1 month. INTERVENTIONS After a water load, dDAVP was administered sublingually as a single dose of oral lyophilisate. Subsequently, blood and urine samples were collected until 7 hours post-administration. MAIN OUTCOME MEASURES Non-compartmental analysis of PK parameters was performed based on dDAVP concentrations in both plasma and urine. To evaluate the effect of dDAVP lyophilisate (PD parameters), the urinary concentration capacity (urine osmolality (mOsm/kg)) and antidiuretic effect (diuresis rate (mL/kg/h)) were calculated. RESULTS The PK data support the need for size-dependent dosing in children. Body weight was shown to be a significant covariate for apparent clearance (CL/F) and apparent volume of distribution (Vd/F). A double absorption peak of dDAVP lyophilisate in the first 2 hours post-administration was demonstrated. CONCLUSIONS For the first time, a double absorption profile of dDAVP lyophilisate was found in children, questioning extrapolation of bioequivalence from adults towards children. Moreover, the need for size-adapted dosing regimens of dDAVP lyophilisate in young children is indicated. TRIAL REGISTRATION NUMBER NTC02584231.
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Affiliation(s)
- Lien Dossche
- Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Gent, Belgium .,Department of Paediatric Nephrology, University Hospital Ghent, Gent, Belgium
| | - Robin Michelet
- Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Gent, Belgium.,Department of Clinical Pharmacy & Biochemistry, Institute of Pharmacy, Freie Universitat Berlin, Berlin, Berlin, Germany
| | - Pauline De Bruyne
- Department of Internal Medicine and Paediatrics, Ghent University, Gent, Belgium
| | - Charlotte Van Herzeele
- Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Gent, Belgium.,Department of Clinical Psychology, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium
| | - Elke Gasthuys
- Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Gent, Belgium
| | - Søren Rittig
- Departments of Clinical Medicine and Paediatrics, Aarhus University Hospital, Aarhus, Denmark
| | - An Vermeulen
- Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Gent, Belgium
| | - Johan Vande Walle
- Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Gent, Belgium.,Department of Paediatric Nephrology, University Hospital Ghent, Gent, Belgium
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13
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Kamperis K. Nocturnal enuresis in children: The role of arginine-vasopressin. HANDBOOK OF CLINICAL NEUROLOGY 2021; 181:289-297. [PMID: 34238464 DOI: 10.1016/b978-0-12-820683-6.00021-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Nocturnal enuresis is the involuntary pass of urine during sleep beyond the age of 5 years. It is a common condition in childhood and has an impact on the child's well-being. Research into the pathophysiology of the condition in the last decades has led to a paradigm shift, and enuresis is no longer considered a psychiatric disorder but rather a maturation defect with a somatic background. An excess urine production during sleep is a common finding in children with enuresis and disturbances in the circadian rhythm of arginine-vasopressin (AVP) is found in the majority of children with nocturnal polyuria. Children with enuresis and nocturnal polyuria lack the physiologic increase in AVP levels during sleep and treatment with the AVP analogue desmopressin can restore this rhythm and lead to dry nights. The reasons for this aberrant circadian AVP rhythm are not established. Furthermore, not all children with enuresis and nocturnal polyuria can be successfully treated with desmopressin suggesting that factors beyond renal water handling can be implicated such as natriuresis, hypercalciuria, and sleep-disordered breathing. The advances in the research of the genetic background of the condition may shed further light on the enuresis pathophysiology.
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Affiliation(s)
- Konstantinos Kamperis
- Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
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14
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Sun C, Xu Y, Luo C, Li Q. Relationship between enuresis and obstructive sleep apnea-hypopnea syndrome in children. J Int Med Res 2020; 48:300060520977407. [PMID: 33290113 PMCID: PMC7727060 DOI: 10.1177/0300060520977407] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 11/02/2020] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE We explored the relationship between enuresis and obstructive sleep apnea-hypopnea syndrome (OSAHS) in children and influencing factors of enuresis with OSAHS. METHODS We recruited 196 children ≥5 years old from the otolaryngology outpatient department, who experienced snoring and underwent nasopharynx lateral radiography and in-laboratory polysomnography. We analyzed correlations between the apnea-hypopnea index (AHI) and lowest oxygen saturation (L-SaO2) with age, body mass index (BMI), tonsil size, and adenoidal-nasopharyngeal (A/N) ratio using the Pearson correlation test. Differences in severe OSAHS prevalence, age, AHI, L-SaO2, tonsil size, and A/N ratio between children with and without enuresis were assessed using the chi-square test and t-test. Risk factors of enuresis were analyzed using logistic regression. Follow-up was conducted to assess remission in children with enuresis after adenotonsillectomy. RESULTS BMI, tonsil size, and A/N ratio were correlated with AHI and L-SaO2. Severe OSAHS prevalence, AHI, tonsil size, and A/N ratio were higher and L-SaO2 were lower in children with enuresis. Logistic regression showed that BMI, AHI, tonsil size, and sleep apnea were risk factors for enuresis. CONCLUSIONS Our study findings showed that enuresis was associated with OSAHS in children. Adenotonsillectomy may improve the symptoms of enuresis.
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Affiliation(s)
- Chen Sun
- Department of ENT, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yingpeng Xu
- Department of ENT, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chenxi Luo
- Department of ENT, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qi Li
- Department of ENT, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Medical School of Nanjing University, Nanjing, Jiangsu, China
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15
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Bastos JM, Rondon AV, de Lima GRM, Zerati M, Schneider-Monteiro ED, Molina CAF, Calado ADA, Barroso U. Brazilian consensus in enuresis-recomendations for clinical practice. Int Braz J Urol 2019; 45:889-900. [PMID: 31408290 PMCID: PMC6844333 DOI: 10.1590/s1677-5538.ibju.2019.0080] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 05/06/2019] [Indexed: 01/14/2023] Open
Abstract
Introduction Enuresis, defined as an intermittent urinary incontinence that occurs during sleep, is a frequent condition, occurring in about 10% of children at 7 years of age. However, it is frequently neglected by the family and by the primary care provider, leaving many of those children without treatment. Despite of many studies in Enuresis and recent advances in scientific and technological knowledge there is still considerable heterogeneity in evaluation methods and therapeutic approaches. Materials and Methods The board of Pediatric Urology of the Brazilian Society of Urology joined a group of experts and reviewed all important issues on Enuresis and elaborated a draft of the document. On September 2018 the panel met to review, discuss and write a consensus document. Results and Discussion Enuresis is a multifactorial disease that can lead to a diversity of problems for the child and family. Children presenting with Enuresis require careful evaluation and treatment to avoid future psychological and behavioral problems. The panel addressed recommendations on up to date choice of diagnosis evaluation and therapies.
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Affiliation(s)
- José Murillo Bastos
- Universidade Federal de Juiz de Fora (UFJF) e Hospital e Maternidade Therezinha de Jesus da Faculdade de Ciências Médicas e da Saúde de Juiz de Fora (HMTJ-SUPREMA), Juiz de Fora, MG, Brasil
| | - Atila Victal Rondon
- Universidade do Estado do Rio de Janeiro (UERJ) e Hospital Federal Cardoso Fontes (HFCF), Rio de Janeiro, RJ, Brasil
| | | | - Miguel Zerati
- Instituto de Urologia e Nefrologia de São José do Rio Preto (IUN) e Faculdade Regional de Medicina(FAMERP), Hospital de Base, São José do Rio Preto, SP, Brasil
| | | | - Carlos Augusto F Molina
- Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), Ribeirão Preto, SP, Brasil
| | | | - Ubirajara Barroso
- Universidade Federal da Bahia (UFBA) e Escola Bahiana de Medicina (BAHIANA), Salvador, BA, Brasil
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16
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Su MS, Xu L, Pan WF, Li CC. Current perspectives on the correlation of nocturnal enuresis with obstructive sleep apnea in children. World J Pediatr 2019; 15:109-116. [PMID: 30446975 DOI: 10.1007/s12519-018-0199-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Accepted: 10/09/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Obstructive sleep apnea (OSA) and nocturnal enuresis (NE) are common clinical problems in children. OSA and NE are thought to be interrelated, but the exact pathophysiological mechanisms are not yet clear. This review aims to explain the possible pathogenesis of NE in children with OSA. DATE SOURCES We have retrieved all relevant original articles from Database that have been published so far, including the prevalence studies of NE and OSA in children, sleep characteristic studies that use polysomnography (PSG) to focus on children with NE, and studies on the relationship between OSA and NE. RESULTS Clinical studies have revealed that the risk of NE in children with OSA was increased compared with that of their healthy peers. This increased risk may be associated with sleep disorders, bladder instability, detrusor overactivity, nocturnal polyuria, endocrine and metabolic disorders, and inflammation. CONCLUSIONS Cardiopulmonary and renal reflex-induced neuroendocrine disorder may play an important role in the mechanism of NE in children with OSA, but this remains to be confirmed by animal studies. Other causes such as oxidative stress and inflammatory responses need to be further researched.
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Affiliation(s)
- Miao-Shang Su
- Department of Pediatric Respiratory Medicine and Sleep Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Li Xu
- Department of Pediatric Respiratory Medicine and Sleep Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Wen-Feng Pan
- Department of Pediatric Respiratory Medicine and Sleep Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Chang-Chong Li
- Department of Pediatric Respiratory Medicine and Sleep Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
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17
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Bijkerk R, Trimpert C, van Solingen C, de Bruin RG, Florijn BW, Kooijman S, van den Berg R, van der Veer EP, Bredewold EOW, Rensen PCN, Rabelink TJ, Humphreys BD, Deen PMT, van Zonneveld AJ. MicroRNA-132 controls water homeostasis through regulating MECP2-mediated vasopressin synthesis. Am J Physiol Renal Physiol 2018; 315:F1129-F1138. [DOI: 10.1152/ajprenal.00087.2018] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Fine-tuning of the body’s water balance is regulated by vasopressin (AVP), which induces the expression and apical membrane insertion of aquaporin-2 water channels and subsequent water reabsorption in the kidney. Here we demonstrate that silencing of microRNA-132 (miR-132) in mice causes severe weight loss due to acute diuresis coinciding with increased plasma osmolality, reduced renal total and plasma membrane expression of aquaporin-2, and abrogated increase in AVP levels. Infusion with synthetic AVP fully reversed the antagomir-132-induced diuresis, and low-dose intracerebroventricular administration of antagomir-132 similarly caused acute diuresis. Central and intracerebroventricular antagomir-132 injection both decreased hypothalamic AVP mRNA levels. At the molecular level, antagomir-132 increased the in vivo and in vitro mRNA expression of methyl-CpG-binding protein-2 (MECP2), which is a miR-132 target and which blocks AVP gene expression by binding its enhancer region. In line with this, treatment of hypothalamic N6 cells with a high-salt solution increased its miR-132 levels, whereas it attenuated endogenous Mecp2 mRNA levels. In conclusion, we identified miR-132 as a first miRNA regulating the osmotic balance by regulating the hypothalamic AVP gene mRNA expression.
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Affiliation(s)
- Roel Bijkerk
- Department of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
- Renal Division, Department of Medicine, Brigham & Women’s Hospital and Harvard Medical School, Boston, Massachusetts
| | - Christiane Trimpert
- Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Coen van Solingen
- Department of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
- Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division of Cardiology, Department of Medicine, New York University Medical Center, New York, New York
| | - Ruben G. de Bruin
- Department of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Barend W. Florijn
- Department of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Sander Kooijman
- Department of Internal Medicine (Endocrinology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Rosa van den Berg
- Department of Internal Medicine (Endocrinology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Eric P. van der Veer
- Department of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Edwin O. W. Bredewold
- Department of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Patrick C. N. Rensen
- Department of Internal Medicine (Endocrinology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Ton J. Rabelink
- Department of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Benjamin D. Humphreys
- Renal Division, Department of Medicine, Brigham & Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- Renal Division, Washington University School of Medicine, St. Louis, Missouri
| | - Peter M. T. Deen
- Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Anton Jan van Zonneveld
- Department of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
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18
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Caldwell PHY, Lim M, Nankivell G. An interprofessional approach to managing children with treatment-resistant enuresis: an educational review. Pediatr Nephrol 2018; 33:1663-1670. [PMID: 29110081 DOI: 10.1007/s00467-017-3830-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 10/17/2017] [Accepted: 10/18/2017] [Indexed: 12/14/2022]
Abstract
Enuresis (intermittent urinary incontinence during sleep in a child aged ≥ 5 years) is commonly seen in paediatric practice. Despite the availability of effective interventions, treatment resistance is encountered in up to 50% of children. In this educational review we attempt to provide insight into the causes of treatment resistance, and offer practical suggestions for addressing this condition using an interprofessional approach. We explore the pathophysiology of and standard treatments for enuresis and discuss why standard treatments may fail. An interprofessional approach to treatment resistance is proposed which utilises the expertise of professionals from different disciplines to address the problems and barriers to treatment. The two interprofessional approaches include a multidisciplinary approach that involves the patient being sent to experts in different disciplines at different times to address their treatment resistance utilising the skills of the respective experts, and an interdisciplinary approach that involves a patient being managed by members of interdisciplinary team who integrate their separate discipline perspectives into a single treatment plan. Although an interdisciplinary approach is ideal, interdisciplinary teams may not be available in all circumstances. Understanding the roles of other disciplines and engaging clinicians from other disciplines when appropriate can still be helpful when treatment resistance is encountered.
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Affiliation(s)
- Patrina H Y Caldwell
- The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia. .,Discipline of Child and Adolescent Health, University of Sydney, Sydney, Australia.
| | - Melissa Lim
- The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia
| | - Gail Nankivell
- The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia
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19
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Kuwertz-Bröking E, von Gontard A. Clinical management of nocturnal enuresis. Pediatr Nephrol 2018; 33:1145-1154. [PMID: 28828529 DOI: 10.1007/s00467-017-3778-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 07/10/2017] [Accepted: 07/13/2017] [Indexed: 01/14/2023]
Abstract
Nocturnal enuresis (NE) is a common health problem. Approximately 10% of 7-year-old children wet the bed regularly during sleep. Enuresis can be categorized into monosymptomatic (MEN) and nonmonosymptomatic (NMEN) forms. MEN occurs without any other symptoms of bladder dysfunction. NMEN is associated with dysfunction of the lower urinary tract with or without daytime incontinence. The rate of comorbid gastrointestinal, behavioral, and emotional disorders is elevated depending upon the subtype of NE. A careful clinical history is fundamental to the evaluation of enuresis. Diagnostic procedures include medical history and psychological screening with questionnaires, bladder and bowel diary, physical examination, urinalysis, ultrasound, and examination of residual urine. The mainstay of treatment is urotherapy with information and psychoeducation about normal lower urinary tract function, the underlying cause of MEN, disturbed bladder dysfunction in the child with NMEN and instructions about therapeutic strategies. Alarm therapy and the use of desmopressin have been shown to be effective in randomized trials. Children with NMEN first need treatment of the underlying daytime functional bladder problem before treatment of nocturnal enuresis. In patients with findings of overactive bladder, besides urotherapy, anticholinergic drugs may be useful.
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Affiliation(s)
- Eberhard Kuwertz-Bröking
- Pediatric Nephrology, University Children's Hospital Münster, Waldeyerstrasse 22, 48149, Muenster, Germany.
| | - Alexander von Gontard
- Department of Child and Adolescent Psychiatry, Saarland University Hospital, 66421, Homburg, Germany
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20
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Gizowski C, Zaelzer C, Bourque CW. Activation of organum vasculosum neurons and water intake in mice by vasopressin neurons in the suprachiasmatic nucleus. J Neuroendocrinol 2018; 30. [PMID: 29405459 DOI: 10.1111/jne.12577] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Accepted: 01/27/2018] [Indexed: 01/24/2023]
Abstract
Previous studies have shown that mice housed under 12:12 h light-dark conditions display a pronounced increase in water intake during a 2-hour anticipatory period (AP) near the end of their active period (Zeitgeber Time ZT; ZT21.5-ZT23.5) compared to the preceding basal period (BP, ZT19.5-ZT21.5). This increased water intake during the AP is not associated with physiological stimuli for thirst, such as food intake, hyperosmolality, hyperthermia, or hypovolemia. Denying mice the water intake supplement during the AP causes them to be dehydrated at wake time. These observations suggest that this form of thirst may be driven by the circadian clock and serve to mitigate the dehydrating effect of absence of water intake during sleep. Here we review recent findings showing that this behavior is mediated by vasopressin (VP) containing neurons in the suprachiasmatic nucleus (SCN). SCN VP neurons project to the organum vasculosum lamina terminalis (OVLT) where the activity dependent release of VP causes excitation of thirst-promoting neurons. SCN VP neurons increase their electrical activity during the AP and the resultant release of VP causes an increase in the action potential firing rate of OVLT neurons. Experiments involving optogenetic control of VP release from the axon terminals of SCN neurons indicate that this network mechanism is necessary and sufficient to mediate pre-sleep water intake in mice. These findings provide insight into the output mechanisms that are used by the central clock to generate circadian rhythms, and reveal that the regulation of water intake contributes to osmoregulatory homeostasis during sleep. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Claire Gizowski
- Centre for Research in Neuroscience, Research Institute, of the McGill University Health Centre, Montreal Ge neral Hospital, 1650 Cedar Avenue, Montreal, QC, Canada, H3G1A4
| | - Cristian Zaelzer
- Centre for Research in Neuroscience, Research Institute, of the McGill University Health Centre, Montreal Ge neral Hospital, 1650 Cedar Avenue, Montreal, QC, Canada, H3G1A4
| | - Charles W Bourque
- Centre for Research in Neuroscience, Research Institute, of the McGill University Health Centre, Montreal Ge neral Hospital, 1650 Cedar Avenue, Montreal, QC, Canada, H3G1A4
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21
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Faerch M, Schroeder MK, Mahler BT, Christensen JH, Kamperis K, Rittig S. Determination of the renal concentration capacity following intravenous administration of dDAVP in healthy humans. Scandinavian Journal of Clinical and Laboratory Investigation 2018; 78:114-119. [PMID: 29361858 DOI: 10.1080/00365513.2017.1420215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The synthetic AVP analogue 1-desamino-8-d-arginine-vasopressin (dDAVP) is used for treatment of polyuric disorders. Lack of commercially available assays limits the usefulness of dDAVP as a diagnostic tool in the assessment of renal concentrating capacity. We aimed to develop a specific radioimmunoassay (RIA) for determination of plasma dDAVP (pdDAVP) in order to investigate the relationship between pdDAVP levels and urine osmolality (Uosm). Further, we aimed to determine the onset, duration, and maximum concentrating capacity following intravenous (i.v.) bolus dDAVP injection. The dDAVP assay was based on a well-established RIA for measurements of AVP. Fourteen healthy subjects (aged 15-18 years) participated. Blood and urine samples were collected prior to and after i.v. bolus of 0.03 µg/kg dDAVP. Diuresis and Uosm was measured for nine hours following dDAVP administration. PdDAVP and Uosm were analyzed.We established a specific RIA for the measurement of pdDAVP. All subjects reached maximal pdDAVP concentration (Cmax) 30 minutes following infusion, and a rise in Uosm after 60 minutes. Maximal Uosm varied between subjects, with no direct correlation to the achieved pdDAVP levels. We found no significant intra-individual variation between two dDAVP infusions and the effect was reproducible in terms of Cmax and maximal Uosm. We characterized the relationship between pdDAVP and Uosm after dDAVP bolus injection in healthy adolescents using our dDAVP assay. Maximal Uosm achieved correlated with the baseline Uosm levels and seemed unrelated to achieved pdDAVP levels. The urine concentrating response was maintained at least eight hours.
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Affiliation(s)
- Mia Faerch
- a Department of Pediatrics , Aarhus University Hospital , Aarhus , Denmark
| | - Marie K Schroeder
- b Pediatric Research Laboratory , Aarhus University Hospital , Aarhus , Denmark
| | - Birgitte T Mahler
- a Department of Pediatrics , Aarhus University Hospital , Aarhus , Denmark
| | - Jane H Christensen
- b Pediatric Research Laboratory , Aarhus University Hospital , Aarhus , Denmark.,c Department of Biomedicine , Aarhus University , Aarhus , Denmark
| | | | - Soren Rittig
- a Department of Pediatrics , Aarhus University Hospital , Aarhus , Denmark
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22
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van der Merwe I, Oosthuizen MK, Ganswindt A, Haim A, Bennett NC. Effects of photophase illuminance on locomotor activity, urine production and urinary 6-sulfatoxymelatonin in nocturnal and diurnal South African rodents. ACTA ACUST UNITED AC 2017; 220:1684-1692. [PMID: 28209805 DOI: 10.1242/jeb.146951] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Accepted: 02/14/2017] [Indexed: 11/20/2022]
Abstract
Effects of photophase illuminance (1, 10, 100 and 330 lx of white incandescent lighting) on daily rhythms of locomotor activity, urine production and 6-sulfatoxymelatonin (6-SMT; 10 versus 330 lx) were studied in nocturnal Namaqua rock mice (Micaelamys namaquensis) and diurnal four-striped field mice (Rhabdomys pumilio). Micaelamys namaquensis was consistently nocturnal (∼90-94% nocturnal activity), whereas considerable individual variation marked activity profiles in R. pumilio, but with activity mostly pronounced around twilight (∼55-66% diurnal activity). The amplitude of daily activity was distinctly affected by light intensity and this effect was greater in M. namaquensis than in R. pumilio Only M. namaquensis displayed a distinctive daily rhythm of urine production, which correlated with its activity rhythm. Mean daily urine production appeared to be attenuated under dim photophase conditions, particularly in R. pumilio The results suggest that the circadian regulation of locomotor activity and urine production possesses separate sensitivity thresholds to photophase illuminance. Micaelamys namaquensis expressed a significant daily 6-SMT rhythm that peaked during the late night, but the rhythm was attenuated by the brighter photophase cycle (330 lx). Rhabdomys pumilio appeared to express an ultradian 6-SMT rhythm under both lighting regimes with comparable mean daily 6-SMT values, but with different temporal patterns. It is widely known that a natural dark phase which is undisturbed by artificial light is essential for optimal circadian function. Here, we show that light intensity during the photophase also plays a key role in maintaining circadian rhythms in rodents, irrespective of their temporal activity rhythm.
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Affiliation(s)
- Ingrid van der Merwe
- Department of Zoology and Entomology, University of Pretoria, Private Bag X20, Hatfield 0028, South Africa
| | - Maria K Oosthuizen
- Department of Zoology and Entomology, University of Pretoria, Private Bag X20, Hatfield 0028, South Africa
| | - Andre Ganswindt
- Endocrine Research Laboratory, Department of Anatomy and Physiology, Ondesterpoort, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa
| | - Abraham Haim
- Israeli Center for Interdisciplinary Studies in Chronobiology, University of Haifa, Haifa 31905, Israel
| | - Nigel C Bennett
- Department of Zoology and Entomology, University of Pretoria, Private Bag X20, Hatfield 0028, South Africa
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Influence of sex on aquaporin1-4 and vasopressin V2 receptor expression in the pig kidney during development. Pediatr Res 2016; 80:452-9. [PMID: 27089501 DOI: 10.1038/pr.2016.94] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 03/15/2016] [Indexed: 11/09/2022]
Abstract
BACKGROUND The ability of the immature kidney to concentrate urine is lower than in adults. The aquaporin (AQP) family and the vasopressin V2 receptor (V2R) play a critical role in the urinary concentrating capacity. Here we investigated a possible sex difference in AQP1, AQP2, AQP3, and AQP4 as well as V2R expression in the fetal pig kidney at different gestation stages. METHODS Pig fetuses were divided into three groups according to gestation age of 60, 80, and 100 d. Quantitative PCR and immunohistochemistry were used to determine the regulation of AQP1, AQP2, AQP3, and AQP4 as well as V2R in the fetal pig kidneys. RESULTS Renal AQP1, AQP2 and AQP3, and V2R expression was increased with gestation age in both sexes, whereas AQP4 expression was unchanged over time. We observed neither sex differences in the AQPs nor V2R expression in the fetal pig kidneys. CONCLUSION AQP1, AQP2, and AQP3, and V2R expression increased with gestation age in the fetal kidney, suggesting that this induction might contribute to the maturation of urinary concentrating capacity. However, no sex differences were observed indicating that sex might not play a role for the maturation of the urinary concentrating activity during kidney development in fetal pig.
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Sinha R, Raut S. Management of nocturnal enuresis - myths and facts. World J Nephrol 2016; 5:328-338. [PMID: 27458562 PMCID: PMC4936340 DOI: 10.5527/wjn.v5.i4.328] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 03/28/2016] [Accepted: 05/11/2016] [Indexed: 02/06/2023] Open
Abstract
Nocturnal enuresis often causes considerable distress or functional impairment to patient and their parents necessitating a multidisciplinary approach from paediatrician, paediatric nephrologist, urologists and psychiatrist. Mechanisms of monosymptomatic nocturnal enuresis are mainly nocturnal polyuria, bladder overactivity and failure to awaken from sleep in response to bladder sensations. Goal oriented and etiology wise treatment includes simple behavioral intervention, conditioning alarm regimen and pharmacotherapy with desmopressin, imipramine and anticholinergic drugs. Symptoms often recurs requiring change over or combination of different modes of
treatment.
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The pathophysiology of monosymptomatic nocturnal enuresis with special emphasis on the circadian rhythm of renal physiology. Eur J Pediatr 2016; 175:747-54. [PMID: 27138767 DOI: 10.1007/s00431-016-2729-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 04/15/2016] [Accepted: 04/25/2016] [Indexed: 01/05/2023]
Abstract
UNLABELLED Nocturnal polyuria in monosymptomatic nocturnal enuresis (MNE) has so far mainly been attributed to a disturbed circadian rhythm of renal water handling. Low vasopressin levels overnight correlate with absent maximal concentrating activity, resulting in an increased nocturnal diuresis with low urinary osmolality. Therefore, treatment with desmopressin is a rational choice. Unfortunately, 20 to 60 % of children with monosymptomatic enuresis are desmopressin-resistant. There is increasing evidence that other disturbed circadian rhythms might play a role in nocturnal polyuria. This review focuses on renal aspects in the pathophysiology of nocturnal polyuria in MNE, with special emphasis on circadian rhythms. Articles related to renal circadian rhythms and enuresis were searched through the PubMed library with the goal of providing a concise review. CONCLUSION Nocturnal polyuria can only partially be explained by blunted circadian rhythm of vasopressin secretion. Other alterations in the intrinsic renal circadian clock system also seem to be involved, especially in desmopressin-resistant enuresis. WHAT IS KNOWN • Disturbance in the circadian rhythm of arginine vasopressin secretion is related to nocturnal polyuria in children with enuresis. • Desmopressin is recommended as a treatment for monosymptomatic nocturnal enuresis, working as a vasopressin analogue acting on V2 receptors in the collecting ducts of the kidney. What is New: • Other renal circadian rhythms might play a role in nocturnal polyuria, especially in desmopressin-resistant case.
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Arda E, Cakiroglu B, Thomas DT. Primary Nocturnal Enuresis: A Review. Nephrourol Mon 2016; 8:e35809. [PMID: 27703953 PMCID: PMC5039962 DOI: 10.5812/numonthly.35809] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2015] [Accepted: 04/30/2016] [Indexed: 01/27/2023] Open
Abstract
Context Nocturnal enuresis or bedwetting is the most common type of urinary incontinence in children. It has significant psychological effects on both the child and the family. Enuresis nocturna is defined as the inability to hold urine during the night in children who have completed toilet training. It is termed as being “primary” if no continence has ever been achieved or “secondary if it follows at least 6 months of dry nights. The aim of this review was to assemble the pathophysiological background and general information about nocturnal enuresis. Evidence Acquisition This review was performed by evaluating the literature on nocturnal enuresis published between 1970 and 2015, available via PubMed and using the keywords “nocturnal enuresis,” “incontinence,” “pediatric,” “review,” and “treatment.” Results Children with nocturnal enuresis produce urine at higher rates during the night, and may have lower bladder capacities. Some children with nocturnal enuresis may also have daytime urgency, frequency, and urinary incontinence. Treatment includes aggressive treatment of accompanying constipation or urinary tract infections, behavioral changes, and medical therapy. Alarm therapy remains the first-line treatment modality for primary nocturnal enuresis. High rates of patient compliance and relapse mean that alternative treatments remain on the agenda. Conclusions Nocturnal enuresis is a common problem that has multifaceted effects on both the child and the family. Due to multiple etiologic factors, nocturnal enuresis is still not clearly defined.
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Affiliation(s)
- Ersan Arda
- Hisar Intercontinental Hospital, Department of Urology, Istanbul, Turkey
| | - Basri Cakiroglu
- Hisar Intercontinental Hospital, Department of Urology, Istanbul, Turkey
- Corresponding author: Basri Cakiroglu, Hisar Intercontinental Hospital, Department of Urology, Istanbul, Turkey. Tel: +90-2165241300, Fax: +90-2165241323, E-mail:
| | - David T. Thomas
- Maltepe University Medical School, Department of Pediatric Surgery, Istanbul, Turkey
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Circadian Rhythm of Glomerular Filtration and Solute Handling Related to Nocturnal Enuresis. J Urol 2016; 195:162-7. [DOI: 10.1016/j.juro.2015.07.079] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/07/2015] [Indexed: 11/18/2022]
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Abstract
Desmopressin is a synthetic analogue of arginine vasopressin, commercially available since 1974. Desmopressin is proven effective for the treatment primary nocturnal enuresis and polyuria. It has been considered by several investigators for the treatment of nocturia with positive results and is now an established treatment for this indication. In this review, we assessed the available clinical data on desmopressin in adult urological disease.
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Sleep fragmentation and periodic limb movements in children with monosymptomatic nocturnal enuresis and polyuria. Pediatr Nephrol 2015; 30:1157-62. [PMID: 25669760 DOI: 10.1007/s00467-015-3044-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2014] [Revised: 12/23/2014] [Accepted: 01/05/2015] [Indexed: 10/24/2022]
Abstract
BACKGROUND Children with nocturnal enuresis (NE) have been found to have sleep fragmentation and a high incidence of periodic limb movements in sleep (PLMS). This study explored the association of monosymptomatic NE and polyuria in relation to fluid intake, bladder volume, number of wet nights, and number of nights with polyuria to the frequency of PLMS and cortical arousals during sleep. MATERIALS AND METHODS Thirty children with monosymptomatic NE and polyuria were enrolled in the study. Enuretic parameters were determined by diaries, forced drinking, uroflow, and ultrasound examination. All subjects participated in one polysomnographic study. The number of cortical arousals and PLMS were compared with those recorded in a former pilot study which included only children with refractory NE. RESULTS Of the 30 children who participated in the study, the mean age was 10.43 ± 3.08 (range 6-16) years, and 23 were boys. The PLMS index was positively associated with the arousal index and the awakening index (p < 0.001). No significant association between the sleep and the enuretic parameters was found. Children with refractory NE showed a significantly higher PLMS index (p < 0.001). CONCLUSIONS We found that PLMS and cortical arousals in sleep were increased in children with monosymptomatic NE and polyuria, without a significant association with the enuretic parameters. These observations suggest the presence of a comorbid mechanism driven by a common, independent pacemaker. We hypothesize the autonomic system, its sympathetic branch, and the dopaminergic system as candidates for this pacemaker.
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Abstract
The objective is to provide a review of nocturnal enuresis (NE), including its epidemiology, etiology, pathophysiology, evaluation, and current management. We also set to provide further insight on the treatment of this condition from the experience derived from patients cared for at our tertiary-care institution. NE affects approximately 15% of all children at 5-year-old, affecting boys more frequently than girls. At our large university tertiary pediatric urology center, NE and incontinence, in general, is one the most common chief complaints prompting urologic care. In this review, we examine the condition in detail, highlighting specific goals of the initial evaluation and treatment. We contrast the commonly implemented treatment recommendations, available from the literature with strategies we have found valuable from our extensive experience in treating patients with this disorder. Using current urologic reference textbooks, book chapters, Medline, journal articles and reviews describing the many aspects of NE were reviewed in order to describe NE and the current practices at our institution. Although, this is not a systematic literature review, it includes relevant available research, institutional experience and urological expert opinion and current practices at a tertiary state health facility. The treatment of NE remains a challenge for many pediatricians and pediatric urologists. This likely stems from the multiple possible etiologies of the disorder. We have established a treatment algorithm at our institution, which we have found successful in the majority of our patients. This consists of starting patients on urotherapy, then offering both the enuresis alarm device and medication therapy as first line treatments, and finally adding anticholingerics for combination therapy. Our hope is with further research the treatment of NE will continue to improve.
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Affiliation(s)
| | - Chad Morley
- Department of Surgery, Division of Urology, West Virginia University Robert C. Byrd Sciences Center, Morgantown, WV, USA
| | - Osama Al-Omar
- Department of Surgery, Division of Urology, West Virginia University Robert C. Byrd Sciences Center, Morgantown, WV, USA
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Mahler B, Kamperis K, Ankarberg-Lindgren C, Frøkiær J, Djurhuus JC, Rittig S. Puberty alters renal water handling. Am J Physiol Renal Physiol 2013; 305:F1728-35. [PMID: 24173356 DOI: 10.1152/ajprenal.00283.2013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
We investigated the influence of sex and puberty stage on circadian urine production and levels of antidiuretic hormone [arginine vasopressin (AVP)] in healthy children. Thirty-nine volunteers (9 prepuberty boys, 10 prepuberty girls, 10 midpuberty boys, and 10 midpuberty girls) were included. All participants underwent a 24-h circadian inpatient study under standardized conditions regarding Na(+) and fluid intake. Blood samples were drawn every 4 h for measurements of plasma AVP, serum 17-β-estradiol, and testosterone, and urine was fractionally collected for measurements of electrolytes, aquaporin (AQP)2, and PGE2. We found a marked nighttime decrease in diuresis (from 1.69 ± 0.08 to 0.86 ± 0.06 ml·kg(-1)·h(-1), P < 0.001) caused by a significant nighttime increase in solute-free water reabsorption (TcH2O; day-to-night ratio: 0.64 ± 0.07, P < 0.001) concurrent with a significant decrease in osmotic excretion (day-to-night ratio: 1.23 ± 0.06, P < 0.001). Plasma AVP expressed a circadian rhythm (P < 0.01) with a nighttime increase and peak levels at midnight (0.49 ± 0.05 pg/ml). The circadian plasma AVP rhythm was not influenced by sex (P = 0.56) or puberty stage (P = 0.73). There was significantly higher nighttime TcH2O in prepuberty children. This concurred with increased nighttime urinary AQP2 excretion in prepuberty children. Urinary PGE2 exhibited a circadian rhythm independent of sex or puberty stage. Levels of serum 17β-estradiol and testosterone were as expected for sex and puberty stage, and no effect on the AVP-AQP2-TcH2O axis was observed. This study found a circadian rhythm of plasma AVP independent of sex and puberty stage, although nighttime TcH2O was higher and AQP2 excretion was more pronounced in prepuberty children, suggesting higher prepuberty renal AVP sensitivity.
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Affiliation(s)
- B Mahler
- Dept. of Pediatrics, Regionshospitalet Randers, Skovlyvej 1, Randers 8930, Denmark.
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Fatouh AAA, Motawie AA, Abd Al-Aziz AM, Hamed HM, Awad MAM, El-Ghany AA, El Bassyouni HT, Shehab MIK, Eid MM. Anti-diuretic hormone and genetic study in primary nocturnal enuresis. J Pediatr Urol 2013; 9:831-7. [PMID: 23246575 DOI: 10.1016/j.jpurol.2012.11.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2012] [Accepted: 11/08/2012] [Indexed: 10/27/2022]
Abstract
OBJECTIVE To investigate whether primary nocturnal enuresis (PNE) is related to a disturbance in anti-diuretic hormone (ADH) secretion pattern at night which may be genetically inherited. SUBJECTS AND METHODS This study included 121 children aged 6-18 years with PNE and 45 matched healthy children as controls. Enuretic children were subjected to genetic evaluation and cytogenetic assessment (n = 99). Assay of ADH levels (9-11 am & 9-11 pm) was performed for cases (n = 99) and controls. RESULTS There was a positive family history in 82.4% (autosomal dominant in 35.4% and autosomal recessive in 64.6%). ADH morning and evening values were reversed in cases vs controls with significant difference in morning level. Reversal of circadian rhythm was present in 71.7% of cases and normal rhythm in 28.3% of them. Morning and evening ADH levels revealed significant difference between patients with reversed rhythm and those with normal one, and with controls. Mode of inheritance had no influence on hormonal level. Chromosomal abnormality was detected in 3 cases with reversed ADH rhythm, involving chromosome 22 in two of them. CONCLUSION PNE could be attributed in part to reversed ADH circadian rhythm which may be linked to chromosome 22.
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Juul KV, Van Herzeele C, De Bruyne P, Goble S, Walle JV, Nørgaard JP. Desmopressin melt improves response and compliance compared with tablet in treatment of primary monosymptomatic nocturnal enuresis. Eur J Pediatr 2013; 172:1235-42. [PMID: 23677249 PMCID: PMC3742424 DOI: 10.1007/s00431-013-1992-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2013] [Accepted: 03/19/2013] [Indexed: 11/24/2022]
Abstract
UNLABELLED Primary nocturnal enuresis is a prevalent childhood condition that can persist into adulthood. Desmopressin is an antidiuretic available as orally disintegrating lyophilisate (melt) or solid tablet. Recent findings suggesting different food interactions and clinical characteristics, including compliance, between desmopressin melt and tablet motivated a post hoc analysis of a previously reported randomised, crossover study. The efficacy of desmopressin melt compared with tablet was evaluated using the International Children's Continence Society (ICCS) responder definitions. Compliance was further analysed using detailed criteria, and the association between efficacy and compliance was examined. In total, 221 patients aged 5-15 years, already receiving desmopressin tablets were randomised to the treatment sequence melt (120/240 μg)/tablet (0.2/0.4 mg) or tablet/melt in two consecutive 3-week periods. The probability of being a responder (partial or full) during either period was significantly more likely with desmopressin melt compared with tablet (odds ratio, 2.0; confidence intervals, 1.07-3.73; p = 0.03). There was no period effect on compliance in the tablet/melt sequence and no difference in the number of completely compliant patients in each formulation group; however, more patients were >75 % compliant in period 1 compared with period 2 in the melt/tablet sequence. Increased compliance was associated with greater reductions in the number of wet nights for both formulations. CONCLUSIONS Desmopressin melt, compared with tablet, improves the probability of being a responder. Switching from tablet to melt formulation increased patient compliance. Increased compliance was associated with increased efficacy. Switching to desmopressin melt may benefit patients with suboptimal responses to desmopressin tablet.
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Affiliation(s)
- Kristian Vinter Juul
- Ferring International PharmaScience Center, Kay Fiskers Plads 11, 2300 Copenhagen, Denmark.
| | | | - Pauline De Bruyne
- />Department of Pediatrics and Medical Genetics, Ghent University, Ghent, Belgium
| | - Sandra Goble
- />Ferring International PharmaScience Center, Kay Fiskers Plads 11, 2300 Copenhagen, Denmark
| | - Johan Vande Walle
- />Pediatric Nephrology Unit, Ghent University Hospital, Ghent, Belgium
| | - Jens Peter Nørgaard
- />Ferring International PharmaScience Center, Kay Fiskers Plads 11, 2300 Copenhagen, Denmark
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Vande Walle J, Rittig S, Bauer S, Eggert P, Marschall-Kehrel D, Tekgul S. Practical consensus guidelines for the management of enuresis. Eur J Pediatr 2012; 171:971-83. [PMID: 22362256 PMCID: PMC3357467 DOI: 10.1007/s00431-012-1687-7] [Citation(s) in RCA: 131] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2011] [Accepted: 01/25/2012] [Indexed: 02/07/2023]
Abstract
UNLABELLED Despite the high prevalence of enuresis, the professional training of doctors in the evaluation and management of this condition is often minimal and/or inconsistent. Therefore, patient care is neither optimal nor efficient, which can have a profound impact on affected children and their families. Once comprehensive history taking and evaluation has eliminated daytime symptoms or comorbidities, monosymptomatic enuresis can be managed efficaciously in the majority of patients. Non-monosymptomatic enuresis is often a more complex condition; these patients may benefit from referral to specialty care centers. We outline two alternative strategies to determine the most appropriate course of care. The first is a basic assessment covering only the essential components of diagnostic investigation which can be carried out in one office visit. The second strategy includes several additional evaluations including completion of a voiding diary, which requires extra time during the initial consultation and two office visits before treatment or specialty referral is provided. This should yield greater success than first-line treatment. CONCLUSION This guideline, endorsed by major international pediatric urology and nephrology societies, aims to equip a general pediatric practice in both primary and secondary care with simple yet comprehensive guidelines and practical tools (i.e., checklists, diary templates, and quick-reference flowcharts) for complete evaluation and successful treatment of enuresis.
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Affiliation(s)
- Johan Vande Walle
- Pediatric Nephrology Unit, Ghent University Hospital, Ghent, Belgium
- Pediatric Nephrology UZ Ghent, De Pintelaan 185, 9000 Ghent, Belgium
| | - Soren Rittig
- Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark
| | - Stuart Bauer
- Department of Urology, Children’s Hospital, Harvard Medical School, Boston, MA USA
| | - Paul Eggert
- University Children’s Hospital, Kiel, Germany
| | | | - Serdar Tekgul
- Department of Urology, Hacettepe University School of Medicine, Ankara, Turkey
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Reduced anti-diuretic response to desmopressin during wet nights in patients with monosymptomatic nocturnal enuresis. J Pediatr Urol 2012; 8:285-90. [PMID: 21514237 DOI: 10.1016/j.jpurol.2011.03.018] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2010] [Accepted: 03/25/2011] [Indexed: 01/29/2023]
Abstract
OBJECTIVE To investigate why not all children with monosymptomatic nocturnal enuresis (MNE) treated with desmopressin give an adequate response. MATERIALS AND METHODS We included 114 children with MNE aged 5-15 years (9.8 ± 0.2 years) who experienced at least 1 wet night and more than 2 dry nights during desmopressin treatment. The patients made home recordings for 2 weeks as baseline and for 2-4 weeks of desmopressin titration. Nocturnal urine production during wet and dry nights, and maximum voided volumes (MVVs) were documented in all patients. RESULTS Sixty-four patients were desmopressin non-responders, 29 were either partial responders or responders, while 21 patients were full responders. Desmopressin reduced nocturnal urine production dramatically during dry nights compared with pre-treatment wet nights. Nocturnal urine production during desmopressin treatment was significantly greater during wet nights compared to dry nights (243 ± 9.32 vs 176 ± 5.31 ml, P < 0.001). There was a highly significant correlation between individual nocturnal urine output and MVV, and dry nights were characterized by nocturnal urine output/MVV ratios well below 1.0. CONCLUSION The anti-enuretic response to desmopressin seems to be dependent upon the degree of reduction in nocturnal urine production. Research on desmopressin bioavailability in children is needed.
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Schultz-Lampel D, Steuber C, Hoyer PF, Bachmann CJ, Marschall-Kehrel D, Bachmann H. Urinary incontinence in children. DEUTSCHES ARZTEBLATT INTERNATIONAL 2011; 108:613-20. [PMID: 21977217 PMCID: PMC3187617 DOI: 10.3238/arztebl.2011.0613] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2010] [Accepted: 06/26/2010] [Indexed: 01/29/2023]
Abstract
BACKGROUND Urinary incontinence (bedwetting, enuresis) is the commonest urinary symptom in children and adolescents and can lead to major distress for the affected children and their parents. Physiological and non-physiological types of urinary incontinence are sometimes hard to tell apart in this age group. METHODS This article is based on selected literature retrieved by a PubMed search and on an interdisciplinary expert consensus. RESULTS AND CONCLUSION Nocturnal enuresis has a variety of causes. The main causative factors in monosymptomatic enuresis nocturna (MEN) are an impaired ability to wake up when the bladder is full, due to impaired or absent perception of fullness during sleep, and an imbalance between bladder capacity and nocturnal urine production. On the other hand, non-monosymptomatic enuresis nocturna (non-MEN) is usually traceable to bladder dysfunction, which is also the main cause of diurnal incontinence. A basic battery of non-invasive diagnostic tests usually suffices to determine which type of incontinence is present. Further and more specific testing is indicated if an organic cause is suspected or if the treatment fails. The mainstay of treatment is urotherapy (all non-surgical and non-pharmacological therapeutic modalities). Some patients, however, will need supportive medication in addition. Urinary incontinence has different causes in children and adults and must therefore be diagnosed and treated differently as well. All physicians who treat the affected children (not just pediatricians and family doctors, but also pediatric nephrologists, urologists, pediatric surgeons, and child psychiatrists) must be aware of the specific features of urinary incontinence in childhood.
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Affiliation(s)
- Daniela Schultz-Lampel
- Kontinenzzentrum Südwest, Schwarzwald Baar-Klinikum, Röntgenstr. 20, 78054 Villingen-Schwenningen, Germany.
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Circadian rhythms in urinary functions: possible roles of circadian clocks? Int Neurourol J 2011; 15:64-73. [PMID: 21811695 PMCID: PMC3138846 DOI: 10.5213/inj.2011.15.2.64] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2011] [Accepted: 06/20/2011] [Indexed: 12/12/2022] Open
Abstract
Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In this review, we briefly introduce circadian clocks and their organization in mammals. We then summarize known daily or circadian variations in urinary function. Importantly, recent findings by others as well as results obtained by us suggest an active role of circadian clock genes in various urinary functions. Finally, we discuss possible research avenues for the circadian control of urinary function.
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Arginine vasopressin plasma levels could indicate children undergoing cardiopulmonary bypass that might benefit from exogenous arginine vasopressin. Crit Care Med 2010; 38:2079-81. [PMID: 20856003 DOI: 10.1097/ccm.0b013e3181f3dd7a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Abstract
Urinary excretion of water and all major electrolytes exhibit robust circadian oscillations. The 24-h periodicity has been well documented for several important determinants of urine formation, including renal blood flow, glomerular filtration, tubular reabsorption, and tubular secretion. Disturbance of the renal circadian rhythms is increasingly recognized as a risk factor for hypertension, polyuria, and other diseases and may contribute to renal fibrosis. The origin of these rhythms has been attributed to the reactive response of the kidney to circadian changes in volume and/or in the composition of extracellular fluids that are entrained by rest/activity and feeding/fasting cycles. However, numerous studies have shown that most of the renal excretory rhythms persist for long periods of time, even in the absence of periodic environmental cues. These observations led to the hypothesis of the existence of a self-sustained mechanism, enabling the kidney to anticipate various predictable circadian challenges to homeostasis. The molecular basis of this mechanism remained unknown until the recent discovery of the mammalian circadian clock made of a system of autoregulatory transcriptional/translational feedback loops, which have been found in all tissues studied, including the kidney. Here, we present a review of the growing evidence showing the involvement of the molecular clock in the generation of renal excretory rhythms.
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Affiliation(s)
- Dmitri Firsov
- Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.
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Abstract
OBJECTIVE To elucidate the background behind the attenuated circadian rhythm of vasoactive hormones in patients with nocturnal enuresis, we tested the hypothesis that enuretic children exhibit an abnormal neuroendocrine response to a baroreflex stimulus during daytime. DESIGN AND PATIENTS In fifteen children and adolescents (aged 13.4 +/- 0.9 years) with severe nocturnal enuresis and 10 age- and sex-matched healthy controls, we performed a 'daytime supine posture' (DSP) study at 10:00 h. MEASUREMENTS Blood was sampled for measurements of plasma vasopressin (P(AVP)), angiotensin II (P(ANGII)), atrial natriuretic peptide (P(ANP)) and serum aldosterone (S(ALDO)), and mean arterial blood pressure (MAP) and heart rate (HR) were measured during the study. RESULTS In both controls and patients with enuresis, DSP at 10:00 h resulted in a marked fall in MAP and HR, a rise in pulse pressure (PP) and estimated plasma volume (PV) and a significant suppression of P(AVP), P(ANGII) and S(ALDO), whereas P(ANP) increased. There were no significant differences between groups in haemodynamic or neuroendocrine responses to DSP. CONCLUSIONS The study showed that children with nocturnal enuresis exhibit a normal neuroendocrine response to supine posture during daytime indicating that baroregulatory mechanisms per se are not playing a significant pathogenic role. Interestingly, the normal neuroendocrine response to supine posture seems to undergo marked circadian changes, as supine posture at night-time is associated with increased levels of vasoactive hormones.
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Affiliation(s)
- Søren Rittig
- Department of Paediatrics, Aarhus University Hospital, Skejby, Aarhus, Denmark.
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Rittig S, Kamperis K, Siggaard C, Hagstroem S, Djurhuus JC. Age related nocturnal urine volume and maximum voided volume in healthy children: reappraisal of International Children's Continence Society definitions. J Urol 2010; 183:1561-7. [PMID: 20176383 DOI: 10.1016/j.juro.2009.12.046] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2009] [Indexed: 11/15/2022]
Abstract
PURPOSE We determined normal, age related reference data regarding maximum voided volume and nocturnal urine production using the same methodology as in clinical practice. MATERIALS AND METHODS A total of 62 girls and 86 boys without enuresis (mean +/- SD age 9.64 +/- 2.63 years, range 3 to 15) completed 4 days (2 weekends) of frequency-volume charts and 14 days of home recording of nocturnal urine production. From these recordings maximum voided volume with and without first morning void was derived for each subject. Also, average nocturnal urine volume with and without nocturia was calculated. Percentiles were produced by dividing the population into 1-year age groups. RESULTS Based on 2,836 daytime voids and 1,977 overnight recordings, maximum voided volume and nocturnal urine volume showed a significant linear relationship with age but not with gender. Maximum voided volume with first morning void was significantly higher than without (403 +/- 137 ml vs 281 +/- 112 ml, p <0.0001) and the 50th percentile line of maximum voided volume with first morning void was 80 to 100 ml higher than Koff's formula (30 x [age + 1] ml). Conversely the 50th percentile of maximum voided volume without first morning void was almost identical to Koff's formula. Regarding nocturnal measurements, nocturia was noted on 128 nights (6.5%) and nocturnal urine volume on nights with nocturia was significantly higher than on nights without nocturia (365 +/- 160 ml vs 248 +/- 75 ml, respectively, p <0.0001). The 97.5th nocturnal urine volume percentile line of healthy children deviated markedly from the current International Children's Continence Society definition of nocturnal polyuria, especially at low and high ages. CONCLUSIONS We demonstrate clearly that the universally used formula 30 x (age + 1) ml is indeed valid for a population of healthy Danish children but only if the first morning void is disregarded. Furthermore, we question the validity of the current International Children's Continence Society formula for nocturnal polyuria (nocturnal urine volume greater than 130% of maximum voided volume for age), and instead we propose the formula, nocturnal urine volume greater than 20 x (age + 9) ml.
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Affiliation(s)
- S Rittig
- Department of Pediatrics, Center for Child Incontinence, Skejby, Aarhus, Denmark.
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Kruse A, Mahler B, Rittig S, Djurhuus JC. Increased Nocturnal Blood Pressure in Enuretic Children With Polyuria. J Urol 2009; 182:1954-60. [DOI: 10.1016/j.juro.2009.04.079] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2008] [Indexed: 10/20/2022]
Affiliation(s)
- Anne Kruse
- Clinical Institute, University of Aarhus and Department of Pediatrics, Aarhus University Hospital (SR), Skejby, Aarhus, Denmark
| | - Birgitte Mahler
- Clinical Institute, University of Aarhus and Department of Pediatrics, Aarhus University Hospital (SR), Skejby, Aarhus, Denmark
| | - Soren Rittig
- Clinical Institute, University of Aarhus and Department of Pediatrics, Aarhus University Hospital (SR), Skejby, Aarhus, Denmark
| | - Jens Christian Djurhuus
- Clinical Institute, University of Aarhus and Department of Pediatrics, Aarhus University Hospital (SR), Skejby, Aarhus, Denmark
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AbdelFatah D, Shaker H, Ismail M, Ezzat M. Nocturnal polyuria and nocturnal arginine vasopressin (AVP): A key factor in the pathophysiology of monosymptomatic nocturnal enuresis. Neurourol Urodyn 2009; 28:506-9. [PMID: 19260089 DOI: 10.1002/nau.20697] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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