Phentermine/tOpiramate to eND Obesity and Uric acid stones Trial (POuND OUT)

摘要 越来越多的证据表明肥胖、糖尿病和肾结石是相互关联的。 疾病在整个美国公民范围内的流行率不断上升。将这三种疾病联系起来 状态是直观的，因为食物量、饮食因素和身体大小都会影响尿液成分和矿物质 排泄物。尿酸肾结石(UAN)，有或没有草酸钙(CO)成分，是第二种 美国最常见的肾结石类型，仅见于酸性尿液(pH值5.8)。患有糖尿病的患者 超重/肥胖导致UAN/COUAN的风险增加6倍，因为他们不能正确地 在他们的尿液中加入缓冲液(铵)。碱疗法，最常见的形式是柠檬酸盐，是最 广泛用于UAN/COUAN的治疗，已有小系列报道，但随访有限 将尿液完全碱化到正常范围--从而消除患者的疾病。尽管有报道称 简单、实用的柠檬酸盐UAN/COUAN管理因患者耐受性差而复杂化，早期 作为在这一人群中使用它的最小的长期证据，停药的有效性是值得怀疑的。 此外，有肾脏疾病的糖尿病患者可能会因服用所需剂量的柠檬酸钾而出现高钾血症， 以及有效的降压药物，如血管紧张素转换酶抑制剂或受体阻滞剂， 会加重高钾血症的风险。最后，这些疗法没有解决两种重要的健康流行病 肥胖和糖尿病是UAN/COUAN的基础和驱动因素。 我们建议进行一项为期18个月的可行性初步研究，名为“苯终端/托吡酯终止肥胖和尿酸” 石头试验“(Pound Out)。我们将30名肥胖和UAN/COUAN患者随机分为两组 FDA批准的减肥药(芬太尼加托吡酯-ER；Qsymia®15 mg/92 mg；Vivus Inc.)或者是 务实的对照组，继续他们的标准用药方案(柠檬酸盐、别嘌醇、饮食等)。 Qsymia®不仅有望提供~10%的总体重减轻，而且还具有独特的副作用 使尿液碱化(使其酸度降低)。这一双管齐下的方法预计将减轻 UAN/COUAN与肥胖的关系，同时建立一类治疗肾结石的新药物 预防。由于30多年来在结石疾病领域没有引入新的药物疗法，我们 我觉得研究目标和研究设计是及时的，可能会为 柠檬酸盐用于尿酸结石形成肥胖患者。

ABSTRACT Mounting evidence indicates that obesity, diabetes mellitus, and kidney stones are inter-connected diseases increasing in prevalence across the entire spectrum of American citizens. Linking these three disease states is intuitive, since food quantity, dietary factors, and body size all affect urinary composition and mineral excretion. Uric acid nephrolithiasis (UAN), with or without components of calcium oxalate (CO), is the second most common kidney stone type in the US and occurs only in acidic urine (pH < 5.8). Diabetics with overweight/obesity have a six-fold increased risk to develop UAN/COUAN because they are unable to properly add buffer (ammonium) to their urine. Alkali therapy, most commonly in the form of citrate salts, is the most widely used treatment for UAN/COUAN and has been reported in small series with limited follow-up to completely alkalinize urine to a normal range – thus, ridding patients of their disease. Despite its reported simplicity, practical UAN/COUAN management with citrate salts is complicated by poor patient tolerance, early cessation, and questionable efficacy as only minimal long-term evidence for its use in this population exists. Furthermore, diabetics with renal disease may develop hyperkalemia on the required doses of potassium citrate, and effective blood pressure medications, such as angiotensin converting enzyme inhibitors or receptor blockers, can worsen the hyperkalemia risk. Finally, these therapies do not address the two important health epidemics that underlie and drive UAN/COUAN: obesity and diabetes. We propose an 18 month, feasibility pilot study entitled, “Phentermine/tOpiramate to eND Obesity and Uric acid stones Trial” (POuND OUT). We will randomize thirty patients with obesity and UAN/COUAN to either an FDA-approved weight loss drug (phentermine plus topiramate-ER; Qsymia® 15mg/92 mg; Vivus Inc.) or a pragmatic control group who remain on their standard medication regimen (citrate salts, allopurinol, diet, etc). Qsymia® is not only expected to provide ~10% total body weight loss but also has a unique side effect of alkalinizing the urine (making it less acidic). This two-pronged approach is expected to reduce the burden of UAN/COUAN and obesity in these individuals while establishing a new class of medications for kidney stone prevention. Since no new drug therapies have been introduced in the area of stone disease in over 30 years, we feel the study objectives and research design are timely and may provide a feasible medication alternative to citrate salts for uric acid stone forming individuals with obesity.