Introduction
In children without sickle cell disease (SCD), nocturnal enuresis, defined as discrete episodes of urinary incontinence during sleep occurring at age five years or older1, occurs more frequently in males2, in children with a family history of nocturnal enuresis, in children with abnormal sleep patterns, and in children with a low socioeconomic status3. Prior studies have demonstrated that nocturnal enuresis is a common comorbidity for children and adolescents with SCD, affecting 20-58% of this population4-6.
Glomerular hyperfiltration and hyposthenuria are two early manifestations of SCD kidney disease, but it is unclear if they are associated with the later development of enuresis7-9. Hyperfiltration refers to a supraphysiologic elevation in the glomerular filtration rate (GFR); hyposthenuria is defined by the inability to concentrate urine to >500 mOsmoles during overnight water deprivation8, 10, 11. A previous clinical trial, BABY HUG, which randomized young children (mean age 13 months) with sickle cell anemia (HbSS/HbSβ0-thalassemia) to receive either placebo or a fixed dose of hydroxyurea (20 mg/kg/day) for two years, established normative values of measured GFR for the 75th and 95th percentiles in a young cohort and demonstrated that 50-70% of young children with sickle cell anemia experience hyposthenuria10.
Prior cross-sectional studies have evaluated laboratory markers of kidney disease at the time nocturnal enuresis was reported. However, the pathology that contributes to the development of nocturnal enuresis likely occurs over time rather than at a single time point. Therefore, we suggest that it is biologically plausible that nocturnal enuresis diagnosed at age 5 years and above may result from clinical and subclinical kidney injury which occurs earlier in childhood. We hypothesized that young children who experience hyperfiltration or hyposthenuria between three to five years of age would be more likely to be diagnosed with nocturnal enuresis after age five years. To test this hypothesis, we performed a longitudinal analysis of laboratory evaluations from patients who were enrolled in two studies at St. Jude Children’s Research Hospital. In addition, because no studies have evaluated the impact of nocturnal enuresis on future kidney disease, we performed a secondary longitudinal analysis to determine if patients with and without nocturnal enuresis had different trajectories in eGFR after five years of age.