PEDIATRIC UROLOGY - CLINICAL

Increased urinary nitrite excretion in primary enuresis: effects of indomethacin treatment on urinary and serum osmolality and electrolytes, urinary volumes and nitrite excretion
Al-Waili NS
Dubai Specialized Medical Center and Medical Research Laboratories, Islamic Establishment for Education, Dubai, United Arab Emirates
BJU Int. 2002; 90:294-301

• Objectives: To assess urinary nitrite excretion, a stable end product of nitric oxide (NO), in patients with enuresis and in normal controls, and to evaluate the effects of indomethacin (a potent prostaglandin synthesis inhibitor) on urinary nitrite excretion, other urinary variables and bladder capacity.
• Patients and Methods: The study comprised 10 patients with primary enuresis and 10 normal comparable controls (age range 6-14 years). Nitrite was assayed in “spot” morning urine samples in both the enuretics and normal controls. Enuretics were then given 50mg indomethacin suppositories each night; urine volume, urinary osmolality and electrolytes, serum osmolality and electrolytes and urinary nitrite were assayed before indomethacin treatment and after 15 days of treatment.
• Results: The mean (sd) urinary nitrite excretion was 24.4 (19.6) micromol/L in normal children and 275.9 (111.2) micromol/L in enuretics (p<0.05). With indomethacin, the urinary nitrite concentration was significantly decreased to 141 (45.1) micromol/L (p<0.05) and associated with a significant reduction in bed-wetting episodes and voiding frequency. The functional bladder capacity was <70% of the predicted value for age in 6 of the patients; they had significant improvements on indomethacin, to values similar to those in patients with a nearly normal functional bladder capacity. Indomethacin decreased the 24-h urinary volume by 41%, the night volume by 40%, clearance of free water by 46% and increased the day: night urinary volume ratio by 55%. The absolute amounts of urinary calcium, magnesium, phosphorus, urea, creatinine, and glucose were lower on indomethacin, although not statistically significantly so. Indomethacin decreased the 24-h urinary and “spot” morning osmolality and osmotic clearance. There were no significant changes in serum osmolality and electrolyte concentrations. Indomethacin also decreased the absolute amount of urinary sodium, chloride and potassium, fractional sodium and potassium excretion, and filtered sodium. Creatinine clearance was decreased by 20% (p>0.05) and normal 24-h urinary protein was significantly lower, by 47%, after indomethacin treatment (p<0.05).
• Conclusion: Urinary nitrite excretion increased significantly in patients with primary nocturnal enuresis; indomethacin markedly reduced bed-wetting episodes and decreased the frequency of voiding in enuretics with small or normal functional bladder capacity, which was associated with a significant decrease in urinary nitrite excretion. Indomethacin reduced bed-wetting by decreasing the urine volume, clearance of free water and urinary electrolytes, and through possible effects on bladder and urethral contraction, by inhibiting NO and prostaglandin synthesis. NO and prostaglandins might be important in the pathogenesis of primary enuresis.
  
  
• Editorial Comment
  Primary enuresis is a common problem of childhood and adolescence with a relatively benign character. However, the psychosocial consequences of the disease are often detrimental. Although many etiologic factors have been implicated as causes of primary enuresis, the exact cause remains obscure in most instances. The most common belief is that the disease has a multifactorial origin, including central nervous system, kidney and bladder, as well as psychosocial and behavioral components.
  This article is significant from 2 standpoints: First, it reviews the literature in detail; kidney and bladder function of the enuretic child are emphasized. Secondly, the authors propose a new concept for the etiology of primary enuresis. The effects of nitric oxide (NO) in the urogenital system have been studied extensively during the last decade, but new effects are being uncovered regularly. From this point of view, the idea of investigating the role of the NO system in enuresis is novel. It is well accepted that there are significant interactions between NO and prostaglandins and similarly, between prostaglandins and anti-diuretic hormone (ADH), but there have been no comprehensive studies of their role in enuresis.
  A weakness of this study is that too many parameters were checked, considering the number of patients (only 10 patients in each of the 2 groups). This limits the generalization of the results, but nonetheless the suggestion that the NO system may be involved in enuresis is worth pursuing further.

Dr. Barry A. Kogan
Chief and Professor of Urology and Pediatrics
Albany Medical College
Albany, New York, USA