Protein intake, nutrition and cardiovascular disease in stage V CKD

描述(由申请人提供)：尽管国家肾脏基金会指南建议血液透析(HD)患者的膳食蛋白质摄入量为1.2g/kg/d，但目前尚不清楚高蛋白质摄入量对这一人群的营养和心血管(CV)影响是有益的还是有害的。我们早期的数据表明，高蛋白质摄入量可能会改善营养状况，但有人认为，肌肉质量低、体型小和血清蛋白质水平低的状态不是饮食摄入量减少的结果，而是代谢性酸中毒、炎症和氧化应激导致的高分解代谢。因此，HD患者高蛋白摄入可能会加重代谢性酸中毒，而不能改善营养状况。蛋白质摄入对心血管疾病的影响也存在争议。营养不良一直被认为是尿毒症心血管疾病的危险因素。另一方面，也有人认为，高蛋白摄入可能会导致血磷和动脉钙化，并伴随着动脉僵硬和心肌应激的后果。因此，HD患者摄入高蛋白饮食的相对风险和益处尚未得到解决。我们假设在整个HD人群中：(1)蛋白质摄入量是肌肉质量的主要决定因素，而炎症、氧化应激和代谢性酸中毒起次要作用；(2)营养不良不是尿毒症心血管疾病的危险因素，因此低蛋白质摄入量不会导致心血管疾病；(3)在另一种极端情况下，高蛋白质摄入量也不是心血管疾病的主要原因，因为在常规临床实践中，与高蛋白质摄入量相关的高血磷通常可以通过使用磷结合物来控制。这一修订应用的具体目的是检查HD患者绝对总蛋白摄入量(TPI以g/天为单位)或饮食蛋白质摄入量与体重(DPI以g/kg/天为单位)与1.营养状态(MRI测量的大腿中部肌肉质量)和功能状态(6分钟步行)和2.动脉僵硬(主动脉脉搏波速度)和心肌损伤(血清心肌肌钙蛋白T)之间的纵向联系。研究人群将是在犹他州和北加州招募的210名HD患者的预期队列。蛋白质摄入量通过膳食记录和尿素动力学模型来测量。分别在基线、6个月、12个月、18个月和24个月测定蛋白质摄入量、6分钟步行、主动脉脉搏波速度和血清心肌肌钙蛋白T，并在基线、12个月和24个月测定大腿中段肌肉质量。蛋白质摄入量与大腿中部肌肉质量、6分钟步行、主动脉脉搏波速度和血清心肌肌钙蛋白T的纵向相关性将在多变量混合效应模型中进行检验。这项研究有足够的力量来测试所提出的终点。与公共健康的相关性：这项研究将在HD患者中检查蛋白质摄入在营养不良和心血管疾病中的作用，这是这些患者最重要的两个问题。

DESCRIPTION (provided by applicant): Even though the National Kidney Foundation guidelines recommend a dietary protein intake >1.2 g/kg/d in hemodialysis (HD) patients, it remains unclear whether high protein intake has beneficial or harmful nutritional and cardiovascular (CV) effects in this population. Our earlier data suggest that high protein intake might improve nutritional status but it has been argued that the state of low muscle mass, small body size and low serum protein levels is not the result of decreased dietary intake, rather hypercatabolism induced by metabolic acidosis, inflammation and oxidative stress. Therefore, a high protein intake in HD patients might be harmful by worsening metabolic acidosis without improving nutritional status. The effects of protein intake on cardiovascular disease are also controversial. Malnutrition has been considered to be a uremic CV risk factor. On the other hand, it also been suggested that high protein intake might t serum phosphorus and arterial calcification with the attendant consequences of arterial stiffness and myocardial stress. The relative risks and benefits of high dietary protein intake in HD patients are therefore unresolved. We hypothesize that in the HD population overall: (1) Protein intake is a major determinant of muscle mass while inflammation, oxidative stress and metabolic acidosis play a lesser role; (2) Malnutrition is not an uremic CV risk factor hence low protein intake does not cause CV disease; and (3) In the other extreme, high protein intake is also not a major cause of CV disease since high serum phosphorus associated with high protein intake can usually be controlled by the use of phosphorus binders in routine clinical practice. The specific aims of this revised application are to examine in HD patients, the longitudinal associations of absolute total protein intake (TPI in g/day) or dietary protein intake normalized to body weight (DPI in g/kg/day) with 1. Nutritional status (mid-thigh muscle mass as measured by MRI) and functional status (6- minute walk) and 2. Arterial stiffness (aortic pulse wave velocity) and myocardial injury (serum cardiac troponin T). The study population will be a prospective cohort of 210 HD patients recruited at Utah and Northern California. Protein intake is measured by dietary records and urea kinetic modeling. Protein intake, 6- minute walk, aortic pulse wave velocity and serum cardiac troponin T will be measured at baseline, 6, 12, 18 and 24 months, Mid-thigh muscle mass will be measured at baseline, 12 and 24 months. The longitudinal associations of protein intake with mid-thigh muscle mass, 6- minute walk, aortic pulse wave velocity and serum cardiac troponin T will be examined in multivariate mixed effects models. The study has adequate power to test the proposed end-points. Relevance to public health: This study will examine in HD patients the role of protein intake in malnutrition and cardiovascular disease, two of the most important problems in these patients.