MECHANISM OF ADAPTING TO DIETARY MANIPULATION IN UREMIA

低蛋白饮食的营养充足性及其机制 正常受试者和CRF患者的成功适应尚未被 仔细检查。 不幸的是，氮平衡（BN）只能测量 总体反应没有显示代谢调整，也没有显示是否长期- 长期适应蛋白质摄入不足将发生在失去 身体蛋白质 在正常受试者中，成功适应LPD包括 减少氨基酸氧化（而不减少蛋白质合成 和/或降解），从而更有效地利用蛋白质。 目前 正常受试者的平均需要量（0.6 g酮酸（VLPD-EAA或VLPD-KA）） 正在用于CRF患者，但CRF中的因素或补充剂 可能会改变对LPD的适应性反应。 在大鼠中，尿毒症酸中毒 增加蛋白质降解，支链氨基酸（BCAA）氧化， 氮排泄 能量代谢也影响蛋白质代谢， 实验性尿毒症 因此，我们计划评估 测定支链氨基酸和蛋白质代谢的倒数池法， 比较使用L[1- 13 C]亮氨酸和[1- 13 C]缬氨酸获得的结果 （具体目标a和2）。 然后，我们将比较短期和长期（6 月）CRF和正常受试者对不同水平的 膳食蛋白质使用BN，BCAA周转，量热法和双标记 水技术（具体目标3和4）。 评估营养 响应VLPD-KA，将确定最佳示踪剂技术， 然后与CRF患者相比， 消耗常规LPD（特定目标5和6）。 如果一个营养 如果发现VLPD-KA饮食具有优势，则将其与VLPD-EAA进行比较 方案（具体目标7和8）。 最后，新陈代谢的影响 尿毒症酸中毒对CRF患者营养反应的影响 具体目标（9）。 CRF患者的营养反应 将进行审查（具体目标9）。 这一全面评价应 提供深入了解调整机制和营养 正常受试者和CRF患者的要求，并将确定因素 这可能会改变蛋白质的需求，（即能量消耗或 酸中毒）。

The nutritional adequacy of low-protein diets (LPD) and the mechanism for successful adaptation in normal subjects and CRF patients have not been carefully examined. Unfortunately, nitrogen balance (BN) only measures overall response without revealing metabolic adjustments nor whether long- term accommodation to an inadequate protein intake will occur after loss of body protein. In normal subjects, successful adaptation to LPD includes a reduction in amino acid oxidation (without a decrease in protein synthesis and/or degradation) yielding more efficient use of protein. Currently, the mean requirement for normal subjects (0.6 g ketoacids (VLPD-EAA or VLPD-KA) are being used in patients with CRF, but factors in CRF or the supplement may change the adaptive response to LPD. In rats, uremic acidosis increases protein degradation, branch-chain amino acid (BCAA) oxidation and nitrogen excretion. Energy metabolism also affects protein metabolism in experimental uremia. We therefore, plan to assess the utility of the reciprocal pool method for determining BCAA and protein metabolism and to compare results obtained using L[1-13C] leucine and [1-13C] valine (Specific Aims a and 2). We will then compare the short- and long-term (6 months) adaptive response of CRF and normal subjects to different levels of dietary protein using BN, BCAA turnover, calorimetry and the double-labeled water technique (Specific Aims 3 and 4). To assess the nutritional response to VLPD-KA, the optimal tracer technique will be determined and then short- and long-term adaptive responses compared to CRF patients consuming a conventional LPD (Specific Aims 5 and 6). If a nutritional advantage is found with the VLPD-KA diet, it will be compared to a VLPD-EAA regimen (Specific Aims 7 and 8). Finally, the influence of the metabolic acidosis of uremia on the nutritional responses of CRF patients will be examined (Specific Aims 9). This nutritional responses of CRF patients will be examined (Specific Aims 9). This comprehensive evaluation should provide insight into mechanisms of adjustment to and nutritional requirements of normal subjects and CRF patients, and will identify factors that may modify protein requirements, (i.e. energy expenditure or acidosis).