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>1.2 g/kg/d，但尚不清楚高蛋白质摄入量对该人群的营养和心血管（CV）影响是有益还是有害。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，低肌肉质量，小体型和低血清蛋白水平的状态不是饮食摄入量减少的结果，而是代谢性酸中毒，炎症和氧化应激引起的高钙血症。因此，HD患者的高蛋白质摄入可能是有害的，会加重代谢性酸中毒，而不会改善营养状况。蛋白质摄入对心血管疾病的影响也存在争议。营养不良被认为是尿毒症CV风险因素。另一方面，也有人认为高蛋白质摄入可能导致血清磷和动脉钙化，并伴随着动脉僵硬和心肌应激的后果。因此，HD患者高膳食蛋白摄入的相对风险和益处尚未得到解决。我们假设在HD人群中：（1）蛋白质摄入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的作用较小;（2）营养不良不是尿毒症CV风险因素，因此低蛋白质摄入不会导致CV疾病;（3）在另一个极端，高蛋白质摄入也不是CV疾病的主要原因，因为与高蛋白质摄入相关的高血清磷通常可以通过使用磷结合剂在常规临床实践中的应用。本修订申请的具体目的是在HD患者中检查绝对总蛋白摄入量（TPI，g/天）或标准化为体重的膳食蛋白摄入量（DPI，g/kg/天）与1.营养状态（通过MRI测量的大腿中部肌肉质量）和功能状态（6分钟步行）和2。动脉僵硬度（主动脉脉搏波速度）和心肌损伤（血清心肌肌钙蛋白T）。研究人群将是在犹他州和北方加州招募的210例HD患者的前瞻性队列。蛋白质摄入量是通过膳食记录和尿素动力学模型来测量的。将在基线、6、12、18和24个月时测量蛋白质摄入量、6分钟步行、主动脉脉搏波速度和血清心肌肌钙蛋白T，将在基线、12和24个月时测量大腿中部肌肉质量。将在多变量混合效应模型中检查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。本研究有足够的把握度来检验拟定的终点。与公共卫生的相关性：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，这是这些患者中最重要的两个问题。

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.