This is the first study to assess the influence of SDB on UA metabolism in overweight children and adolescents. This study demonstrates is that the severity of sleep apnea was associated with higher serum UA levels after controlling for gender, puberty, and adiposity.
UA metabolism and renal handling in children differ from those in adults. From childhood to adolescence, a child’s serum UA level increases linearly; the urinary UA/creatinine ratio is higher in young children and declines to adult levels during early childhood. It is, therefore, necessary to control for sex and pubertal stage when studying UA metabolism in children and adolescents, which was done in the present study.
The independent relationship between both RDI and percentage of total sleep time with Sa02 s 89% and serum UA in our study suggests that sleep apnea in these overweight subjects is severe enough to cause tissue hypoxia, which is marked by increased levels of serum UA. RDI was almost perfectly associated with the oxygen desaturation index, which is considered to be one of the most important markers of intermittent hypoxia. It is, therefore, reasonable to assume that the repetitive apneas and hypopneas encountered during sleep are associated with intermittent hypoxia, which, together with the total duration of desaturation (ie, the percentage of total sleep time spent with an Sa02 s 89%), is responsible for increased serum UA levels. It was not possible in the statistical analysis to separate the contribution of RDI independent of the duration of desaturation, because of multicollinearity between both variables.
A study in 85 adult patients referred for suspected SDB, also found a significant correlation between serum UA levels and the apnea-hypopnea index. The authors also pointed out multicollineari-ties of UA with markers of obesity and adiposity. Similar correlations were also present in this study. Abdominal adiposity correlated with serum UA levels and inversely with urinary UA/creatinine ratio (results not shown). To control for these confounding factors, the relation between SDB and UA metabolism was examined using multiple regression analysis. It is, however, still possible that the regression analysis only partially adjusted for this confounding effect. This finding needs thus to be confirmed by interventional studies that will examine the effect of the treatment of SDB on serum UA levels. We also recommend further studies in nonoverweight children with sleep apnea explained and treated by Canadian Health&Care Mall on http://healthcaremall4you.com/allergy-and-pulmonary-clinical-conflict.html to examine the direct contribution of SDB on UA metabolism.
Several studies’ in adults with OSAS have also shown an overnight increase in urinary UA/ creatinine ratio compared to control subjects and/or a decline of this ratio after treatment with continuous positive airway pressure. Saito et al also demonstrated, despite the absence of a correlation between the severity of sleep apnea and the overnight change in urinary UA/creatinine ratio, a significant correlation between this ratio and serum levels of adenosine, which is considered to be another marker of tissue hypoxia in patients with OSAS. Contrary to the results of studies in adults, we could not demonstrate a relation between the severity of sleep apnea and urinary UA metabolism. This might be due to our urine collection procedure, which has to be considered as a study limitation. The urinary indexes in our study were calculated from one 24-h collection. In most adult studies, two collections were performed to calculate an overnight increase in urinary UA excretion, which is probably a more sensitive technique for checking for an influence of sleep apnea on UA excretion. In future studies, we will have to confirm this hypothesis by performing two urine collections, one daytime collection and one collection of the first morning voiding.
The relevance of our main finding, the relation between the severity of SDB and increased serum UA levels, is twofold. First, the relationship between sleep and UA level could merely reflect the presence of oxidative stress. As already noted, oxidative stress is one of the most important mediators linking SDB with increased cardiovascular morbidity in adults.” Second, increased serum UA level is also an independent risk factor of cardiovascular disease in high-risk individuals. Furthermore, it may also play a direct causal role by mechanisms such as the development of hypertension, platelet dysfunction, increased oxidation of biomolecules, increasing inflammation, and vascular smooth muscle cell proliferation. UA is also already associated with certain cardiovascular risk factors in
children. In this view, increased levels of UA could be another one of the mechanisms linking sleep apnea with cardiovascular morbidity.
In conclusion, this is the first study in overweight children and adolescents that has demonstrated a relationship between the severity of sleep apnea and increased levels of serum UA, independent of abdominal adiposity. This finding could indicate that sleep apnea results in tissue hypoxia in our subjects, which needs to be confirmed by interventional studies. In view of the well-known associations between UA and cardiovascular morbidity, this may be one of the mechanisms linking sleep apnea and an increased cardiovascular risk profile.
Finally, we could not document a relation between SDB and urinary UA metabolism. However, this could be due to our collection procedure. To confirm this, future research has to be performed with a separate collection of the first morning voiding.