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: 7376068
• 负责人: RAJNISH MEHROTRA
• 金额: $ 10.78万
• 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: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376068
• 关键词: EFFECT; ARTERIAL; PH; BALANCE; PATIENTS

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 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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。蛋白质-能量营养不良（PEM）是晚期慢性肾功能衰竭患者和接受维持性透析（MD）患者的常见发现。在终末期肾脏疾病的偶发和流行患者中，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病理生理学中发挥作用，但有四个因素似乎特别重要：低营养摄入、全身性炎症、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值从较低的正常值增加到较高的正常值可能导致患者营养状况的改善，包括那些接受持续腹膜透析（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含量的减少有关，泛素是一种在骨骼肌蛋白分解代谢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，但很少有对APD患者氮或蛋白质代谢的系统分析。考虑到这些因素，我们建议验证以下假设：在接受APD治疗的MD患者中，动脉pH值为7.43-7.45的净蛋白平衡明显高于动脉pH值为7.36-7.38的净蛋白平衡。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。这项提议有两个具体目的。首先，我们将比较8名APD患者在两种不同动脉血pH水平下的n平衡。其次，我们将检验其他次要假设，以研究动脉pH在正常范围内变化的营养后果。具体来说，我们将比较（13）c -亮氨酸转换，并检查骨骼肌活检，以评估选定的合成代谢蛋白（胰岛素样生长因子I、IGF-I、IGF-II、IGF-I受体）的基因和蛋白质表达，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值水平下的营养状况进行额外评估；然而，由于研究时间较短，我们预计不会观察到受试者的营养状况或身体成分有任何显著变化。在初始筛选和磨合阶段后，受试者将在GCRC住院共41天。动脉pH值的每一阶段将持续20天，第一个pH值阶段（低或高）将使用随机数表选择。在整个研究期间，饮食、身体活动和透析处方将保持不变并受到严格控制。用含有35 mmol/L乳酸的腹膜透析液，加/不加NH(4)Cl，对受试者进行透析，获得下动脉pH值。用含有40 mmol/L乳酸的腹膜透析液，在/不添加NaHCO的情况下进行透析，可以获得较高的动脉pH值(3)。亮氨酸转换研究、肌肉活检和营养评估将在每个动脉pH期结束时进行。