EFFECT OF ARTERIAL PH ON N-BALANCE OF PATIENTS UNDERGOING AUTOMATED PERITONEAL

动脉PH值对接受自动化腹膜手术患者N平衡的影响

• 批准号: 7606172
• 负责人: RAJNISH MEHROTRA
• 金额: $ 5.94万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606172
• 关键词: Bicarbonates; Biopsy; Blood; Body Composition; Catabolism; Chronic Kidney Failure; Classification; Computer Retrieval of Information on Scientific Projects Database; Dialysis Solutions; Dialysis patients; Dialysis procedure; Diet; End stage renal failure; Equilibrium; Functional disorder; Funding; Gene Expression; Gene Proteins; Grant; Hormones; Inflammation; Institution; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Intake; Leucine; Maintenance; Messenger RNA; Metabolic; Metabolic acidosis; Modality; Muscle; Muscle Proteins; Nitrogen; Normal Range; Numbers; Nutrient; Nutrition Assessment; Nutritional Study; Nutritional status; Patients; Peritoneal; Peritoneal Dialysis; Phase; Physical Dialysis; Physical activity; Play; Protein-Energy Malnutrition; Proteins; Randomized; Receptor Gene; Reporting; Research; Research Personnel; Resistance; Resources; Role; Running; Skeletal Muscle; Skeletal system; Source; Supplementation; Testing; Ubiquitin; United States National Institutes of Health; Venous; day; design; myostatin; outcome forecast; prescription document; prescription procedure; prospective; protein expression; protein metabolism

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Protein-energy malnutrition (PEM) is a common finding in patients with advanced chronic renal failure and those undergoing maintenance dialysis (MD). The presence of PEM in both incident and prevalent patients with end-stage renal disease portends a poor short- and long-term prognosis. Numerous factors have been identified that appear to play a role in the pathophysiology of PEM in MD patients but four appear to be particularly important: low nutrient intake, systemic inflammation, metabolic acidosis and resistance to the effects of anabolic hormones. There is accumulating evidence that suggests an increase in arterial pH from lower normal to higher normal values may result in improvement in the nutritional status of patients, including those undergoing continuous peritoneal dialysis (CPD). Indeed, a recent report demonstrated that an increase in arterial pH and venous bicarbonate levels from low to high normal values was associated with a decrease in mRNA content of ubiquitin, a protein that plays an important role in the catabolism of skeletal muscle proteins. Even though automated peritoneal dialysis (APD) is the most rapidly growing dialysis modality, very few systematic analyses of nitrogen or protein metabolism of patients undergoing APD have been performed. Given these consideration, we propose to test the following hypothesis: In MD patients undergoing treatment with APD, an arterial pH of 7.43-7.45 is associated with a significantly more positive net protein balance than an arterial pH of 7.36-7.38. To test this hypothesis, we have designed a prospective, randomized crossover metabolic balance study. The proposal has two specific aims. First, we will compare the N-balances in 8 subjects treated with APD at two different levels of arterial blood pH. Second, we will test other secondary hypotheses to study the nutritional consequences of a change in arterial pH within the normal range. Specifically, we will compare (13)C-leucine turnover and examine skeletal muscle biopsies to evaluate the gene and protein expression of selected anabolic proteins (insulin like growth factor I, IGF-I, IGF-II, IGF-I receptor) and gene expression of an anti-anabolic (myostatin) protein. We will make additional assessment of nutritional status at each level of arterial pH; however, we do not anticipate observing any significant changes in the nutritional status or body composition of the subjects because of the short duration of the study. After an initial period of screen and run-in phase, subjects will be hospitalized in the GCRC for a total duration of 41 days. Each phase of arterial pH will last 20 days, and the first pH phase (low or high) will be chosen using a table of random numbers. The diet, physical activity and dialysis prescription will be constant and tightly controlled during the entire study period. The lower arterial pH will be obtained by dialyzing subjects with peritoneal dialysis solution containing 35-mmol/L of lactate with/without supplementation with NH(4)Cl. The higher arterial pH will be obtained by dialyzing subjects with peritoneal dialysis solution containing 40-mmol/L of lactate with/without supplementation with NaHCO(3). Leucine turnover studies, muscle biopsy and nutritional assessment will be performed at the end of each arterial pH phase.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 蛋白质能量营养不良（PEM）是晚期肾衰竭和接受维持透析（MD）患者的普遍发现。在末期肾脏疾病的事件和普遍的患者中，PEM的存在预示了短期和长期预后。已经确定了许多因素在MD患者中似乎在PEM的病理生理学中起作用，但四个似乎尤其重要：营养摄入量低，全身性炎症，代谢性酸中毒和对合成代谢激素作用的耐药性。有累积的证据表明，动脉pH值从较低的正常值增加到较高的正常值可能会导致患者的营养状况提高，包括患者的腹膜连续透析（CPD）。实际上，最近的一份报告表明，动脉pH值和静脉碳酸氢盐水平从低正常值增加与泛素mRNA含量的降低有关，泛素的mRNA含量降低，这种蛋白质在骨骼肌蛋白的分解代谢中起重要作用。尽管自动腹膜透析（APD）是透析最快的透析模态，但对正在接受APD的患者的氮或蛋白质代谢的系统分析很少。考虑到这些考虑，我们建议检验以下假设：在接受APD治疗的MD患者中，与7.36-7.38的动脉pH相比，动脉pH值为7.43-7.45的净蛋白质平衡明显高得多。 为了检验这一假设，我们设计了一项前瞻性，随机的跨界代谢平衡研究。该提案有两个具体的目标。 首先，我们将比较用APD在两个不同水平的动脉血液中治疗的8名受试者中的N能量。其次，我们将检验其他次要假设，以研究正常范围内动脉pH变化的营养后果。具体而言，我们将比较（13）C-达氨酸周转率并检查骨骼肌活检，以评估选定的合成代谢蛋白（如生长因子I，IGF-I，IGF-I，IGF-II，IGF-I受体）的基因和蛋白质表达，并评估抗烷基（肌脂蛋白）蛋白的基因表达。我们将在每个动脉pH的每个级别上对营养状况进行额外评估；但是，我们预计由于研究持续时间较短，因此观察到受试者的营养状况或身体组成的任何重大变化。 在筛查和跑阶段的初期阶段之后，受试者将在GCRC中住院41天。 动脉pH的每个阶段将持续20天，并使用随机数表选择第一pH相（低或高）。在整个研究期间，饮食，体育锻炼和透析处方将保持恒定并严格控制。下动脉pH值将通过透析受试者用腹膜透析溶液透析溶液，其中含有35-mmol/L的乳酸溶液，并不补充NH（4）Cl。 较高的动脉pH值将通过透析受试者用腹膜透析溶液进行透析受试者，其中含有40毫米/L的乳酸，含有/不补充NAHCO（3）。亮氨酸更新研究，肌肉活检和营养评估将在每个动脉pH相结束时进行。