Following the yellow brick road: understanding urinary system dysfunction in sickle cell disease
Krystle D Frazier, Neha BhasinAbstract
Background
Enuresis is reported to affect 20-50% of individuals with sickle cell disease (SCD) and is associated with poor quality of life. Persistent enuresis, into adolescence and adulthood is associated with urinary bladder and renal dysfunction. Despite this high prevalence and link to urinary system dysfunction, the pathophysiology of enuresis in SCD is poorly understood. Currently, there are no studies investigating the effect of hydroxyurea (HU) on enuresis. This prospective study aimed to investigate associations between hydroxyurea usage, SCD screening labs and enuresis.
Methods
Participants were recruited from the pediatric SCD program at UCSF-Oakland during routine clinic visits. Consenting participants completed a questionnaire on enuresis, water intake, lower urinary tract symptoms (LUTS), sleep disturbances, and constipation. Study staff reviewed medical histories and HU optimization was assessed using the clinical team’s criteria. Routine laboratory tests, cystatin-C levels, and alpha-thalassemia genotyping were obtained.
Results
Fifty-three participants with SCD, aged 5.5–24 years (mean 13.7 ± 4.6), were enrolled. Genotypes included HbSS (n = 30), HbSC (n = 9), HbSβ+ (n = 8), HbSβ⁰ (n = 3), and other rare sickle hemoglobinopathies (n = 3). Only 4 participants (8%) met DSM-V criteria for enuresis, while 23 (43%) reported LUTS, including urinary frequency, urgency, and post-micturition dribbling. Among participants with urinary symptoms (LUTS or enuresis), the majority did not report daily fluid intake exceeding 64 oz (n = 36, 69%). Urinary symptoms were not associated with constipation or obstructive sleep apnea; however, an association was observed with snoring (n = 15, p = 0.039). Participants with urinary symptoms demonstrated higher platelet counts (median 433 × 10³/µL, 95%CI: 354–512; p = 0.001) and white blood cell counts (WBC; 9.98 ×10³/µL, 8.5–11.45; p = 0.039). No significant differences were observed in fetal hemoglobin percentage (HbF%), cystatin-C levels, or urine microalbumin-to-creatinine ratio. Among participants prescribed HU (n = 34), 17 (50%) were using HU as prescribed (mean HbF 23 ± 8%), 1 demonstrated improving HU usage (HbF 9.3%), 8 had suboptimal usage (mean HbF 11± 5%), and 16 were working on optimizing their HU usage (mean HbF 17 ± 7%). Pearson’s chi-square testing did not show a statistically significant association between HU usage category and the presence of urinary symptoms (χ²(3)=5.18, p = 0.058).
Conclusions
Urinary symptoms rather than the DSM-V based definition of enuresis are prevalent among children with SCD. Urinary symptoms in SCD are associated with snoring, and elevations in platelets and WBC. HbF was not associated with urinary symptoms; however, our study is not powered for this analysis. Rigorous, prospective studies are necessary to assess the therapeutic benefit of HU for urinary symptoms in SCD.