Omega 3 Fatty Acid Supplementation in Diabetic Kidney Disease

描述（由申请人提供）：我们描述了一项随机对照临床试验的计划，以确定补充 omega-3 脂肪酸对患有糖尿病和肾病（定义为存在蛋白尿）的成人尿蛋白排泄的影响。在美国，糖尿病是终末期肾病的最常见原因。预防或减缓糖尿病肾病进展的主要方法包括改变生活方式和旨在实现和维持血糖、血压和胆固醇目标的药物治疗。我们对糖尿病肾病发病机制了解的进展为测试新疗法奠定了基础，例如 Omega-3 脂肪酸补充剂，这些疗法影响炎症、氧化应激和内皮功能障碍等疾病的潜在机制。我们将进行一项单中心随机试验，测试 30 名患有糖尿病和蛋白尿的成年人在 3 个月内每日补充 omega-3 脂肪酸（0、0.9 或 3.6 克 DHA/EPA）对尿蛋白排泄的有效性。在交叉试验中，参与者将被随机分配每日服用四粒 omega-3 脂肪酸补充剂胶囊或外观相同的安慰剂（玉米油）。每位参与者每天将接受 0、0.9 或 3.6 克 EPA DHA 剂量。通过多种技术测量的尿蛋白排泄量将是主要结果变量。将探索尿蛋白排泄变化与 eGFR、血压、氧化和炎症标志物变化以及尿蛋白排泄模式变化之间的关联，并将其与干预相关。拟议的研究非常适合 R21 资助机制。首先，它有足够的能力使我们能够确定干预导致的尿蛋白排泄的显着变化。其次，我们测量反映潜在肾小球和肾小管间质病理生理学的解释变量。最后，了解补充 omega-3 脂肪酸对肾损伤和功能标志物的短期影响是为具有临床意义的终点的大规模临床试验提供理由的必要的第一步（下一步）。公共健康相关性：在本申请中，我们描述了一项随机安慰剂对照临床试验的计划，以测试每日补充 omega-3 脂肪酸（鱼油）对减少成人糖尿病患者尿蛋白排泄和其他肾损伤生物标志物的益处以及肾脏疾病的证据。在交叉研究设计中，参与者将随机接受每天 0、0.9 和 3.6 克的 omega-3 脂肪酸（鱼油）或安慰剂（玉米油），持续三个 6 周的周期。我们希望 omega-3 脂肪酸补充剂可以添加到当前的疗法中，帮助防止肾脏疾病的进展，肾脏疾病是糖尿病的一种常见且具有破坏性的并发症。

DESCRIPTION (provided by applicant): We describe plans for a randomized controlled clinical trial to determine the effects of omega-3 fatty acid supplementation on urine protein excretion in adults with diabetes and kidney disease defined by the presence proteinuria. Diabetes is the most common cause of end-stage-kidney disease in the United States. Primary approaches to prevent or slow the progression of diabetic kidney disease include lifestyles changes and pharmacological therapy aimed at achieving and maintaining glucose, blood pressure and cholesterol goals. Advances in our understanding of the pathogenesis of diabetic kidney disease have laid the foundation for testing novel therapies, such as omega-3 fatty acid supplements, that affect underlying mechanisms of the disease such as inflammation, oxidative stress and endothelial dysfunction. We will conduct a single center randomized trial to test the effectiveness of daily supplementation of omega-3 fatty acids (0, 0.9 or 3.6 g DHA/EPA) over 3 months in 30 adults with diabetes and proteinuria, on urine protein excretion. Participants will be randomized in a crossover trial to four daily capsules of omega-3 fatty acid supplements or to identical appearing placebos (corn oil). Each participant will receive either a daily dose of 0, 0.9 or 3.6 g/day EPA+DHA . Urine protein excretion, measured by several techniques will be the primary outcome variable. The association between change in urine protein excretion with change in eGFR, blood pressure, markers of oxidation and inflammation, and change in urine protein excretion patterns will be explored and related to the intervention. The proposed study is ideally suited for the R21 funding mechanism. First, it is adequately powered to allow us to determine significant changes in urine protein excretion as a result of the intervention. Secondly, we measure explanatory variables reflective of the underlying glomerular and tubulointerstitial pathophysiology. Finally, understanding the short-term effects of omega-3 fatty acid supplementation on markers of kidney damage and function is a necessary first step in providing the justification for a large scale clinical trial with clinically meaningful endpoints (next step). PUBLIC HEALTH RELEVANCE: In this application we describe plans for a randomized placebo-controlled clinical trial to test the benefits of daily omega-3 fatty acids (fish oils) supplements at reducing urine protein excretion and other biomarkers of kidney injury in adults with diabetes and evidence for kidney disease. Participants will be randomize to receive 0, 0.9, and 3.6 grams per day of omega-3 fatty acids (fish oils) or placebo (corn oil) each day for three 6 week periods in a cross-over study design. We are hopeful that omega-3 fatty acid supplements may add to current therapies that help protect against progression of kidney disease, a common and devastating complication of diabetes.