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: 7952226
• 负责人: RAJNISH MEHROTRA
• 金额: $ 12.75万
• 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: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7952226
• 关键词: Bicarbonates; Biopsy; Blood; Body Composition; Catabolism; Chronic Kidney Failure; Classification; Clinical Research; 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; Insulin-Like-Growth Factor I Receptor; Intake; Leucine; Maintenance; Messenger RNA; Metabolic; Metabolic acidosis; Modality; Muscle; Muscle Proteins; Nitrogen; Normal Range; Nutrient; Nutrition Assessment; Nutritional Study; Nutritional status; Patients; Peritoneal; Peritoneal Dialysis; Phase; Physical activity; Play; Protein-Energy Malnutrition; Proteins; Randomized; Receptor Gene; Reporting; Research; Research Personnel; Resistance; Resources; Role; Running; Skeletal Muscle; Source; Supplementation; Testing; Ubiquitin; United States National Institutes of Health; Venous; design; myostatin; outcome forecast; 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 drecrease 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 underoing 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 thenormal 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 lactat 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 蛋白质-能量营养不良（PEM）是慢性肾衰竭晚期患者和维持性透析（MD）患者的常见发现。在终末期肾病患者中，PEM的存在预示着短期和长期预后不良。已经确定了许多因素似乎在MD患者的PEM的病理生理学中起作用，但其中四个因素似乎特别重要：低营养摄入、全身炎症、代谢性酸中毒和对合成代谢激素作用的抵抗。越来越多的证据表明，动脉pH值从正常值下限升高至正常值上限可能会改善患者的营养状况，包括接受连续性腹膜透析（CPD）的患者。事实上，最近的一份报告表明，动脉pH值和静脉碳酸氢盐水平从低到高的正常值的增加与泛素mRNA含量中的drecrease相关，泛素是一种在骨骼肌蛋白质的catalysis中起重要作用的蛋白质。尽管自动腹膜透析（APD）是发展最快的透析方式，但很少对APD患者的氮或蛋白质代谢进行系统分析。鉴于这些考虑，我们建议检验以下假设：在接受APD治疗的MD患者中，动脉pH值为7.43-7.45与净蛋白平衡的正相关性显著高于动脉pH值为7.36-7.38。 为了验证这一假设，我们设计了一项前瞻性、随机交叉代谢平衡研究。该提案有两个具体目标。 首先，我们将比较在两个不同的动脉血pH值水平下接受APD治疗的8例受试者的N平衡。其次，我们将检验其他次要假设，以研究动脉pH值在正常范围内变化的营养后果。具体而言，我们将比较13 C-亮氨酸周转并检查骨骼肌活检以评估所选合成代谢蛋白（胰岛素样生长因子I、IGF-I、IGF-II、IGF-I受体）的基因和蛋白表达以及抗合成代谢肌肉生长抑制素蛋白的基因表达。我们将对每个动脉pH值水平的营养状态进行额外评估;但是，由于研究持续时间较短，我们预计不会观察到受试者的营养状态或身体组成发生任何显著变化。 在筛选和导入期的初始阶段后，受试者将在GCRC住院治疗，总持续时间为41天。 动脉pH的每个阶段将持续20天，将使用随机数字表选择第一个pH低或高阶段。在整个研究期间，饮食、体力活动和透析处方将保持恒定并严格控制。通过使用含35 mmol/L乳酸盐（补充/不补充NH（4）Cl）的腹膜透析液对受试者进行透析，获得较低的动脉pH值。 通过使用含40 mmol/L乳酸盐的腹膜透析液（补充/不补充NaHCO）对受试者进行透析，可获得较高的动脉pH值（3）。将在每个动脉pH阶段结束时进行亮氨酸转换研究、肌肉活检和营养评估。