MECHANISM OF ADAPTING TO DIETARY MANIPULATION IN UREMIA

低蛋白饮食(LPD)的营养充分性及其机制 正常受试者和慢性肾衰患者的成功适应尚未得到 仔细检查过。不幸的是，氮平衡(BN)只衡量 总体反应没有透露代谢调整，也没有长期- 对蛋白质摄入量不足的长期适应将在失去 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(不减少蛋白质合成 和/或降解)产生更有效地利用蛋白质。目前， 正常人的平均需要量(0.6克酮酸(VLPD-EAA或VLPD-KA) 用于CRF患者，但CRF中的因子或补充剂 可能改变对LPD的适应性反应。大鼠尿毒症酸中毒 增加蛋白质降解、支链氨基酸(BCAA)氧化和 氮气排泄。能量代谢也会影响蛋白质代谢。 实验性尿毒症。因此，我们计划评估 支链氨基酸和蛋白质代谢测定的倒置池法 L[1-13C]亮氨酸和[1-13C]缬氨酸测定结果的比较 (具体目标a和2)。然后我们将比较短期和长期(6 3个月)慢性肾功能衰竭和正常人对不同水平的 用BN、BCAA周转量热法和双标记法测定膳食蛋白质 水技术(具体目标3和4)。为了评估营养状况 对VLPD-KA的响应，将确定最佳示踪技术并 然后将短期和长期适应性反应与CRF患者进行比较 消耗传统的LPD(具体目标5和6)。如果一种营养 VLPD-KA饮食的优势被发现，它将与VLPD-EAA进行比较 养生法(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 审查(具体目标9)。慢性肾功能衰竭患者的营养反应 将进行审查(具体目标9)。这项综合评估应该 提供对适应和营养的机制的洞察 正常受试者和慢性肾功能衰竭患者的需求，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).