In this study, the risk factors for JIA complicated with hyperuricemia included the following: slightly high systolic pressure, obesity (high BMI), older age, active sacroiliitis status, and SASP application. After the incidence of hyperuricemia, the Scr level was relatively higher, but not beyond the normal upper limit, which indicated a potential risk of renal impairment. The urate crystals gradually formed after 6 months of hyperuricemia, indicating a higher risk of gout.
Due to the limited sample size, the 5 factors significantly related to the groups of interest could not be further analyzed through logistic regression to observe whether they were correlated.
The increase in the systolic pressure and obesity can be treated as predictive risk factors for hyperuricemia; which has also been mentioned as the risk factors by several large data epidemiological investigations associated with adult and child hyperuricemia cases[2, 3]. The food intake of obesity patients is greater than their calorie consumption, which results in the accumulation of excessive fat in the subcutaneous, abdominal, or internal organs, which in turn may add to the total amount of nucleic acid to be processed through purine metabolism that may lead to increase in the UA synthesis[4]. The incidence of hyperuricemia may affect the renal functions, as has also been reported by several local and remote studies[5, 6]. High UA level leads to systemic hypertension and high pressure, high perfusion, and renal fibrosis in glomerulus through RAS, which ultimately results in renal impairment [7, 8]. In this study, after 6 months of hyperuricemia, the dual-energy CT examination of pediatric gout with diagnostic value revealed a gradual formation of urate crystals; despite the lack of symptoms, the examination predicted the development of gout.
However, no incidence of hyperuricemia in JIA active sacroiliitis individuals and pediatric patients with SASP treatment has yet been reported in local or foreign studies, which is consistent with our clinical findings. Since the majority of non-biological DMARDs selected for the JIA active sacroiliitis group was SASP, we inferred that the real cause leading to hyperuricemia is SASP instead of the active sacroiliitis group. Furthermore, because this JIA group included older patients, age was not an independent risk factor.
SASP is an azo complex of 5-aminosalicylic acid (5-ASA) and a sulfa pyridine, after it was applied orally and reached the colon, the azo bond cleaved subject to the effect of the intestinal bacterium–azoreductase. The released 5-ASA is the main active component of SASP, but approximately 80% of it remains in the colon where it plays the role of mucosal antibacterial anti-inflammation and immunological suppression, as well as exhibits anti-inflammatory effect by inhibiting the synthesis of prostaglandin and other inflammatory mediators such as leukotriene, leukocytes IL-1. Most of the released sulfa pyridine are absorbed into the colon, and, after the acetylation in the liver, they are excreted with the urine in the form of free sulfonamide, acetylation, hydroxylation, or glucuronic acid derivatives [10]. This phenomenon may be attributed to the excretion of several acidifying substances competing against UA from the urine, which leads to an increase in the UA level. In case of insufficient water consumed during this period, which is necessary to maintain the high urine flow, it may lead to the incidence of crystalluria and aggravate the renal impairment. Therefore, excretion of UA is reduced. The specific mechanism involved in this phenomenon remains to be clarified.
The appropriate therapeutic program for JIA pediatric patients with obesity and high blood pressure was applied to reduce the application of SASP or the addition of alkalizing urine drugs as much as possible so as to reduce the incidence of hyperuricemia, renal impairment, and accumulation of urate crystal at the joints, which together further aggravate joint symptoms.