To the best of our knowledge,this is the first study on the use of urate-lowering drugs after bariatric surgery. In this study, patients in both groups achieved better control of SUA levels at 6 months after bariatric surgery, Most DTG subjects experienced a smoother and more gradual decrease in SUA levels over the course of 1 month, avoiding acute attacks of gout due to excessive fluctuations in uric acid. All patients were free of gout attacks during the period of 3-6 months after surgery,and they showed significant decreases in both SUA and BMI at 6 months after surgery.
Obesity and metabolic syndrome have been prospectively studied as clinically relevant risk factors for hyperuricemia and gout[22], and patients with severe obesity tend to have a higher risk of developing hyperuricemia[23-26]. As a chronic disease,patients diagnosed with hyperuricemia or gout may require long-term or even lifelong medication, with medication compliance and side effects being major issues. Therefore, the use of urate-lowering drugs for hyperuricemia remains controversial[27]. Furthermore, traditional drug therapy may have limitations for patients with obesity and hyperuricemia, as treatment with urate-lowering drugs alone is often less effective and may have certain drawbacks[28, 29].
Current research has demonstrated the effectiveness of weight loss achieved through dietary intervention or weight loss surgery in lowering SUA levels and preventing gout attacks[9, 13, 28-30].Several pieces of research evidence have suggested that bariatric surgery can decrease the long-term incidence of hyperuricemia and gout, and even enable certain patients to discontinue urate-lowering therapy[13, 31]. Moreover,besides weight loss, the reduction in SUA may be linked to a reduction in the systemic inflammatory response associated with the metabolic syndrome (This response is triggered by changes in adipokines and pro-inflammatory cytokines resulting from bariatric surgery) .Additionally, it may also be associated with the reduction in insulin resistance[32], which can be combined with other reported benefits of bariatric surgery[33, 34].Nevertheless, the recurrence of postoperative hyperuricemia and the repeated reports of acute gout attacks should not be ignored.
There is documented evidence that high preoperative SUA levels and suspension of urate-lowering therapy are important risk factors for acute gout attacks[35, 36].Our study discovered that bariatric surgery followed by urate-lowering medication in patients with a preoperative diagnosis of hyperuricemia and a history of acute gout attacks resulted in reduced short-term fluctuations in SUA levels, thereby lowering the frequency of gout attacks in the short term. Moreover, we also found that bariatric surgery was effective in reducing the morbidity of hyperuricemia, as this will be demonstrated in our subsequent long-term follow-up.
One potential cause of postoperative SUA level fluctuations in patients with hyperuricemia that we cannot ignore is the perioperative diet. According to the Chinese Expert Consensus on Precision Obesity Metabolic Surgery (2022 Edition)[37],our center recommends a specific diet plan for patients following surgery. Patients are asked to consume a liquid diet for 2 weeks after surgery,gradually transitioning to a dregs-free, full liquid diet that is easy to digest. From 3 to 4 weeks after surgery,patients are asked to consume a semi-liquid diet with easily digestible foods. From 1 to 2 months after surgery, patients are recommended to consume a soft diet that includes a variety of high-quality protein sources such as meat, fish and protein supplements. However,this type of diet may increase uric acid levels by enhancing purine metabolism, and may lead to gout attacks [38]. The catabolic state induced by perioperative caloric restriction has also been suggested as a potential cause of gout attacks[29]. The American Society for Metabolic and Bariatric Surgery (ASMBS) and the International Federation for Surgery of Obesity and Metabolic Diseases (IFSO) advocate a high-protein, low-carbohydrate, and low-fat postoperative diet [39, 40], However, low-carbohydrate diets induce mobilization of fatty acids from abdominal and hepatic stores, which, together with increased protein intake, are associated with increased purine release and concomitant ketogenic state, formation of β-hydroxybutyrate and acetoacetate, impairing renal excretion of uric acid and consequently increasing the frequency of acute gout attacks[41]. In contrast to this dietary pattern, the traditional Chinese diet practices place more emphasis on grain and vegetable intake,with a lower protein content. However,soup consumption may lead to micronutrient deficiencies after surgery[42, 43].Therefore, in addition to the standard dietary recommendations, we also advise our patients to control their protein intake and receive appropriate rehydration therapy. Beyond that, in our center, patients without previous hyperuricemia also experience short-term fluctuations in SUA after bariatric surgery, for whom it may be clinically relevant to investigate the impact of perioperative diet on short-term fluctuations in SUA.
Our study had several limitations that need to be acknowledged. First, the retrospective design and the small sample size due to our strict inclusion/exclusion criteria (Table 1) may limit the generalizability of our findings. Second, due to the retrospective nature of the study and the specificity of bariatric surgery patients, we lacked synovial fluid and imaging tests for gout diagnosis, hence,the diagnosis of gout was based mainly on the patient's symptoms and complaints. In future studies, we will try to collect synovial fluid specimens and imaging evidence to support the diagnosis. Third, it is acknowledged that various bariatric surgery procedures can yield diverse effects on patients’ absorption[44, 45].However, this study specifically focused on laparoscopic sleeve gastrectomy, with no inclusion of patients who underwent Roux-en-Y gastric bypass(RYGB)or other types of surgeries. Therefore, the potential impacts of other weight loss surgery methods on drug absorption were not considered. Finally, the follow-up period was relatively short, and more than 80 percent of the patients included in this study were women; since gout is more common in men, this may limit the possibility of generalizing our findings. To address these limitations,further prospective studies with larger sample sizes and longer follow-up periods,including multicenter collaborations, are needed to better assess the effects of medication on SUA control and gout attack prevention in patients with hyperuricemia undergoing bariatric surgery.