Plant-Focused Nutrition in Patients with Diabetes and Chronic Kidney Disease (PLAFOND Study): A Pilot/Feasibility Study

摘要 慢性肾脏疾病(CKD)影响着10%-15%的美国成年人，包括30%-40%的糖尿病患者 糖尿病(DM)与不良预后有关，通常进展为需要透析或移植。 所有患有慢性肾脏病的美国人中有一半也患有糖尿病。虽然传统和新兴的药物疗法通常是 用于慢性肾脏病合并糖尿病(CKD/DM)，饮食干预的协同作用一直不是很好 检查过了。糖尿病患者通常推荐低碳水化合物、低脂肪饮食，而低蛋白饮食(LPD) 推荐用于非糖尿病CKD，并日益重视植物来源的蛋白质。证据 提示动物蛋白含量较高的高蛋白饮食可能会导致肾小球高滤过和 CKD/DM患者肾功能下降较快。仍然存在重大争议的是关于 CKD/DM中植物性饮食的潜在风险与益处，指南仍基于专家 意见。考虑到管理糖尿病的传统饮食限制，人们担心以植物为基础的 低密度脂蛋白可能会导致蛋白质-能量浪费和高钾血症，而这些饮食可能确实是最 有益于CKD/DM患者，因为与非糖尿病患者相比，他们的CKD进展更快。 目前，临床实践指南提供了关于剂量的相互矛盾的建议(低与 CKD/DM患者膳食蛋白质摄入量(DPI)高)和来源(植物与动物)。考虑到之前的饮食试验 慢性肾脏病，例如1994年肾脏疾病饮食的改变(MDRD)研究排除了慢性肾脏病/糖尿病，并且没有 研究植物和动物蛋白质的最佳比例，迫切需要一种严格的 饮食干预研究，以检查以患者为中心的植物性饮食在CKD/DM中的有效性和安全性。 本着PAS 20-160(针对NIDDK疾病的临床试验的小R01)的精神，我们建议进行一项试点 可行性随机对照试验，与患者在两个CKD的常规随访平行进行 加州大学欧文分校内的诊所，以测试实施工厂的可行性和安全性- CKD/DM(Plafond)膳食中的集中营养，DPI为0.6-0.8g/kg/d，包括2/3植物性成分 来源，与护理标准肾脏饮食相比，1/3植物来源和低钾含量，由 营养师对120名CKD/DM 3-5期患者进行了为期6个月的调查。我们将确定是否 长期饮食与标准护理肾脏饮食可以通过饮食的一致分离来坚持。 蛋白质和植物性比例在3个月和6个月时。我们还将检查营养状况、身体状况 性能，身体成分，以及使用传统指标和连续的血糖测量 血糖监测，而其他生化参数和患者报告的结果包括CKD相关 症状也将被研究。除了提供患者所需的可行性和安全性数据外- 未来多中心试验的设计和实施所需的中心饮食方案，我们建议的研究 将通过重振慢性肾脏病/糖尿病饮食管理的关键作用而产生重大的直接影响。

SUMMARY Chronic kidney disease (CKD) affects 10-15% of US adults including 30-40% of persons with diabetes mellitus (DM), is associated with poor outcomes, and often progresses to requiring dialysis or transplantation. Half of all Americans with CKD also have DM. While traditional and emerging pharmacotherapies are often used in CKD with diabetes (CKD/DM), the synergistic role of dietary interventions has not been well examined. Low-carbohydrate low-fat diets are often recommended in DM, whereas low-protein diets (LPDs) are recommended for non-diabetic CKD with increasing emphasis on plant-based protein sources. Evidence suggests that high-protein diets with greater animal protein content may lead to glomerular hyperfiltration and faster decline in renal function in patients with CKD/DM. There remains major controversy regarding the potential risks vs. benefits of plant-based diets in CKD/DM, for which guidelines remain based on expert opinion. Given conventional dietary restrictions for the management of DM, there is concern that plant-based LPDs may lead to protein-energy wasting and hyperkalemia, whereas these diets may indeed be most beneficial in patients with CKD/DM given their faster rates of CKD progression as compared to non-diabetics. At present, clinical practice guidelines provide conflicting recommendations regarding the amount (low vs. high) and source (plant vs. animal) of dietary protein intake (DPI) in CKD/DM. Given that prior dietary trials in CKD such as the 1994 Modification of Diet in Renal Disease (MDRD) study excluded CKD/DM and did not examine the optimal proportion of plant vs. animal-based proteins, there is urgent unmet need for a rigorous dietary intervention study to examine the efficacy and safety of patient-centered plant-based diets in CKD/DM. In the spirit of PAS 20-160 (Small R01s for Clinical Trials Targeting NIDDK Diseases) we propose a pilot feasibility randomized controlled trial, conducted in parallel with patients' routine follow-up visits at two CKD clinics within the University of California Irvine, to test the feasibility and safety of implementing a Plant- Focused Nutrition in CKD/DM (PLAFOND) diet with a DPI of 0.6-0.8 g/kg/d comprised of >2/3 plant-based sources, vs. standard-of-care renal diet with <1/3 plant-sources and low-potassium content, administrated by dietitians, over a 6-month period in 120 patients with CKD/DM stage 3-5. We will determine whether the PLAFOND diet vs. the standard-of-care renal diet can be adhered to with consistent separation in dietary protein and plant-based proportions at 3- and 6-months. We will also examine nutritional status, physical performance, and body composition, as well as glycemic measures using traditional metrics and continuous glucose monitoring, while other biochemical parameters and patient-reported outcomes including CKD-related symptoms will also be studied. In addition to providing the requisite feasibility and safety data of patient- centered dietary regimens needed for the design and conduct of future multi-center trials, our proposed study will have major immediate impact by reinvigorating the critical role of dietary management of CKD/DM.