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.