Standard urotherapy in children with nocturnal enuresis (NE) is first-line treatment according to the current International Children's Continence Society (ICCS) guidelines. ICCS defines standard urotherapy as information and demystification, instruction in how to resolve lower urinary tract dysfunction, lifestyle advice, registration of symptoms and voiding habits, and support and encouragement. These interventions often are time consuming and some aspects of urotherapy, such as fluid restrictions, can be a frustrating process for a child, which emphasizes the importance of clarifying their relevance. The purpose of this review is to perform a systematic search in literature to evaluate the use of standard urotherapy in the treatment of children with primary NE (PNE). A systematic literature search was conducted in MEDLINE, Embase, and CENTRAL based on the key concepts of standard urotherapy and NE. We identified 2,476 studies. After a systematic selection process using the Covidence tool, 39 studies were included. The quality of the studies was assessed by the QualSyst Checklist. Our protocol adheres to the PRISMA statement and was registered in PROSPERO database (CRD42020185611). Most of the 39 included studies scored low in quality. All studies combined several urotherapy interventions and studied different study populations. Twenty-two randomized controlled trials (RCTs) were included, which reported 0-92% of children being dry after urotherapy treatment. Three RCTs, all individualizing and optimizing drinking and voiding during the day and practicing optimal toilet posture, scored higher in quality based on the QualSyst score, and reported few children experiencing complete resolution of NE (5-33%). Eight studies compared the efficacy of urotherapy to a control group, however, conflicting results were found. This systematic review presents available literature in the field of standard urotherapy in the treatment of children with PNE. One possible explanation for low efficacy rates of urotherapy in NE is the large heterogeneity of the study populations and interventions. Additionally, the intervention period and the intensity of intervention can have an impact on the outcome. The number of clinical studies on standard urotherapy in children with NE is limited and many of them are of poor quality. High quality research in a well-defined NE population is needed to establish the role of standard urotherapy in first-line treatment of children with NE or as an add-on to other first line treatments. We conclude that at present there is insufficient evidence for recommending standard urotherapy to children with PNE as a first line treatment modality.

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.

Although nocturnal polyuria in patients with monosymptomatic enuresis can largely be explained by the decreased nocturnal vasopressin secretion hypothesis, other circadian rhythms in the kidney also seem to have a role. We recently documented an absent day/night rhythm in a subgroup of desmopressin refractory cases. We explore the importance of abnormal circadian rhythm of glomerular filtration and tubular (sodium, potassium) parameters in patients with monosymptomatic enuresis. In this retrospective study of a tertiary enuresis population we collected data subsequent to a standardized screening (International Children's Continence Society questionnaire), 14-day diary for nocturnal enuresis and diuresis, and 24-hour concentration profile. The study population consisted of 139 children with nocturnal enuresis who were 5 years or older. Children with nonmonosymptomatic nocturnal enuresis were used as controls. There was a maintained circadian rhythm of glomerular filtration, sodium, osmotic excretion and diuresis rate in children with monosymptomatic and nonmonosymptomatic nocturnal enuresis, and there was no difference between the 2 groups. Secondary analysis revealed that in patients with nocturnal polyuria (with monosymptomatic or nonmonosymptomatic nocturnal enuresis) circadian rhythm of glomerular filtration, sodium and osmotic excretion, and diuresis rate was diminished in contrast to those without nocturnal polyuria (p <0.001). Circadian rhythm of the kidney does not differ between patients with nonmonosymptomatic and monosymptomatic enuresis. However, the subgroup with enuresis and nocturnal polyuria has a diminished circadian rhythm of nocturnal diuresis, sodium excretion and glomerular filtration in contrast to children without nocturnal polyuria. This observation cannot be explained by the vasopressin theory alone.