The natural history of enuresis and nocturia in children and young adults with SCA and the relationship of these complications to morbidity are poorly defined. Our study supports previous reports of the higher prevalence of enuresis and nocturia among children and young adults with SCA compared with the general population. We also found that the prevalence of enuresis declines throughout childhood, but continues to be a persistent problem for many young adults with SCA. Unlike enuresis, the prevalence of nocturia remains relatively constant throughout childhood and young adulthood ().
The mechanism underlying the increased rate of enuresis among children with SCA is not clearly delineated. Previously, repetitive infarcts to the renal medulla were thought to be responsible for the high prevalence of enuresis in children with SCA. These infarcts purportedly affected the ability of the kidney to concentrate urine, resulting in a form of nephrogenic diabetes insipidus and subsequent high urine volumes.1
However, when Readett et al.
compared the urine osmolality of eneuretic children with SCA with those without enuresis, they did not find a significant difference in urine osmolality after a water deprivation test. Instead, the authors reported that children with SCA and enuresis had a lower maximum functional bladder capacity compared with phenotype-, age-, and gender-matched controls.12
Furthermore, other factors may contribute to enuresis among children with SCA, such as social and environmental factors and decreased arousal during sleep.12
Few studies have examined therapeutic interventions for enuresis or nocturia in children with SCA. Figueroa et al.
studied desmopressin acetate in a group of 10 children with SCA and enuresis.7
Enuretic episodes resolved in 4 participants and improved in 2 more children. Although the results suggest a benefit for desmopressin acetate, no definitive conclusions can be drawn from this small observational study. Further studies are needed to elucidate more carefully the pathogenesis of enuresis and nocturia in SCA, and afterward, therapeutic studies aimed at potential targets can be conducted.
In our study, we examined one potential etiology of enuresis and nocturia among individuals with SCA, vasoocclusion– related morbidity. Previous studies have not rigorously examined the relationships among SCA-related morbidity, such as pain and ACS episodes, and enuresis and nocturia. Participants in our cohort were observed for an average of 2.8 years after enuresis was reported and we did not find an increased rate of pain or ACS episodes in children or young adults with enuresis or nocturia compared with those without enuresis or nocturia. Despite these negative findings, enuresis and nocturia may still be due to SCA-related factors. Other morbidities common in individuals with SCA, such as pulmonary hypertension, leg ulcers, and priapism, are not clearly associated with pain and ACS episodes.17,18
As expected in a cohort study that was not designed specifically to address the prevalence of enuresis, there are limitations to our study. Although the International Children’s Continence Society broadly defines enuresis as intermittent incontinence while sleeping, enuresis is typically categorized as monosymptomatic (no history of lower urinary tract symptoms, excluding nocturia, and without a history of bladder dysfunction) and non-monosymptomatic enuresis (often due to bladder overactivity).19
Owing to our study design, we could not determine whether lower urinary tract symptoms were present in our study population. The ability to classify enuresis into monosymptomatic and non-monsymptomatic is important for understanding the mechanism of enuresis in this population. Another limitation of our study is that many children who were eligible for our cohort did not complete the questions related to enuresis and nocturia on the annual history form, and thus selection bias may have influenced our results. The CSSCD was an observational, natural history study and individuals who did not complete all study-related activities were still included in the analysis. Finally, our prevalence data were determined with a cross-sectional as opposed to longitudinal design. Cross-sectional prevalence data may reflect differences between individuals in the cohort instead of changes within an individual over time. In this study, we did not perform a longitudinal analysis because there were too few individuals with repeated responses to the questionnaire. Despite these limitations, our study provides evidence suggesting that enuresis and nocturia are a problem not only for children with SCA, but also for adults.