The pathophysiology of monosymptomatic nocturnal enuresis with special emphasis on the circadian rhythm of renal physiology.

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.

Hypercalciuria is related to osmolar excretion in children with nocturnal enuresis.

PURPOSE: We evaluated the incidence of hypercalciuria, defined as urinary calcium-to-creatinine ratio greater than 0.21 mg/mg, in children with nocturnal enuresis, and the association with concurrent values of diuresis and osmolar excretion. MATERIALS AND METHODS: A total of 550 children admitted to a tertiary university center were included in the study. A 24-hour urine collection was performed in 8 sampling periods for measurement of calcium excretion, osmolality and diuresis. RESULTS: Of the children with nocturnal enuresis 12% had 24-hour hypercalciuria. Up to 29% of the timed urine samples exhibited hypercalciuria. There was a significant correlation between calcium excretion and nocturnal diuresis volume (polyuria), low urinary osmolality, and increased sodium and osmolar excretion of nighttime urine samples (all p <0.001). CONCLUSIONS: Patients referred to a tertiary enuresis center have a high incidence of hypercalciuria. However, the significant correlation between hypercalciuria and osmolar excretion and diuresis suggests that it is a comorbid factor rather than a primary pathogenic factor. As such, we cannot confirm the data from Italian studies relating nocturnal enuresis to primary hypercalciuria, and suggest instead an association with nutritional intake.

Management of hypertension in children and adolescents.

Hypertension has been recognized as an important health issue in the pediatric population over the past years. This emphasizes the need for an organized and effective plan for diagnosis and management. This review provides information to guide physicians through a structured approach to (1) screen children for hypertension during routine visits; (2) use normative blood pressure tables for diagnosis and classification; (3) perform a clinical evaluation to identify the presence of risk factors, comorbidities and/or target organ damage; and (4) initiate an individualized plan of care that includes follow-up blood pressure measurement, therapeutic lifestyle changes and - if necessary - pharmacological therapies.

Nocturnal enuresis and nocturia, differences and similarities - lessons to learn?

This review highlights the current views on and differences and similarities between nocturnal enuresis (NE) in children and nocturia in adults, which might be a guidance to elucidate the missing links in our knowledge. In both conditions, a genetic factor is suspected. Reduced bladder capacity and nocturnal polyuria are the main underlying lower urinary tract-related conditions. There is a link with sleep disorders, although it is not clear whether this is a cause or consequence. Physical and mental health are comprised in both conditions, however, in different ways. In NE, constipation and attention deficit disorder are the most important comorbidities and the effect on mental health and quality of life is mainly through the negative impact on self-esteem. In nocturia, cardiovascular disease and fall injuries are important comorbidities, mainly affecting the older nocturia population; personal distress and depression are consequences of the related poor sleep quality. For both conditions, treatment is often inadequate and a more individualized approach seems to be necessary. The main difference between NE and nocturia seems to be the difference in arousal to bladder stimuli, suggesting that sleep characteristics might be a key factor in these conditions.

Neuropsychological functioning related to specific characteristics of nocturnal enuresis.

INTRODUCTION/BACKGROUND: There is a high comorbidity demonstrated in the literature between nocturnal enuresis and several neuropsychological dysfunctions, with special emphasis on attention deficit hyperactivity disorder (ADHD). However, the majority of the psychological studies did not include full non-invasive screening and failed to differentiate between monosymptomatic nocturnal enuresis (MNE) and non-MNE patients. OBJECTIVE: The present study primarily aimed to investigate the association between nocturnal enuresis and (neuro)psychological functioning in a selective homogeneous patient group, namely: children with MNE and associated nocturnal polyuria (NP). Secondly, the study investigated the association between specific characteristics of nocturnal enuresis (maximum voided volume, number of wet nights and number of nights with NP) and ADHD-inattentive symptoms, executive functioning and quality of life. STUDY DESIGN: The psychological measurements were multi-informant (parents, children and teachers) and multi-method (questionnaires, clinical interviews and neuropsychological testing). RESULTS: Thirty children aged 6-16 years (mean 10.43 years, SD 3.08) were included. Of them, 80% had at least one psychological, motor or neurological difficulty. The comorbid diagnosis of ADHD, especially the predominantly inattentive presentation, was most common. According to the teachers, a low maximum voided volume (corrected for age) was associated with more attention problems, and a high number of nights with NP was associated with more behaviour-regulation problems. No significant correlations were found between specific characteristics of enuresis and quality of life. Details are demonstrated in Table. DISCUSSION: The children were recruited from a tertiary referral centre, which resulted in selection bias. Moreover, NP was defined as a urine output exceeding 100% of the expected bladder capacity for age (EBC), and not according to the expert-opinion-based International Children's Continence Society norm of 130% of EBC. The definition for NP of a urine output exceeding 100% of the EBC is more in line with the recent findings of the Aarhus group. CONCLUSIONS: For children with MNE and associated NP, a high comorbidity with the predominantly inattentive presentation of ADHD was demonstrated. Children experienced problems with daytime functioning in relation to their wetting problem at night. According to the teachers, a low maximum voided volume was associated with more attention problems, and a high number of nights with NP was associated with more behaviour-regulation problems. Although comorbidity is still the appropriate word to use, the observation favours a more complex pathogenesis of enuresis with a common pathway in the central nervous system, including: neurotransmitters, influencing neuropsychological functioning as well as sleep, circadian rhythm of diuresis and bladder function control.