Retained Organic Solutes and Clinical Outcomes in Hemodialysis

血液透析中残留的有机溶质和临床结果

• 批准号: 8113661
• 负责人: NEIL R. POWE
• 金额: $ 10.04万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-09 至 2011-08-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8113661
• 关键词: Address; Albumins; Amines; Biological; Biological Assay; Cardiovascular system; Caring; Characteristics; Chronic Kidney Failure; Clinical; Clinical Trials; Cognition; Cohort Studies; Collaborations; Cresol; Cresols; Desire for food; Development; Dialysis patients; Dialysis procedure; End stage renal failure; Event; Freezing; Future; General Population; Glyoxal; Goals; Guanidines; Hemodialysis; Hospitalization; Indican; Indoles; Inorganic Sulfates; Intervention; Kidney; Kidney Failure; Laboratories; Lead; Longevity; Methods; Methylamines; Modality; Morbidity - disease rate; N,N-dimethylarginine; Outcome; Participant; Patient Self-Report; Patients; Persons; Plasma; Protein Binding; Pyruvaldehyde; Randomized Clinical Trials; Recruitment Activity; Reporting; Research Design; Restless Legs Syndrome; Sampling; Science; Septicemia; Specimen; Symptoms; Testing; Toxin; Unspecified or Sulfate Ion Sulfates; Urea; Work; cognitive function; experience; high risk; improved; methylamine; mortality; programs; prospective; repository; solute

DESCRIPTION (provided by applicant): Treatment for end-stage renal disease (ESRD) with hemodialysis, the most common renal replacement modality, is currently aimed at clearing urea. Hemodialysis patients continue to experience high rates of morbidity and mortality far in excess of the general population. The recent HEMO clinical trial revealed that enhanced urea clearance did not lead to improved mortality. There are a large number of organic solutes, other than urea, that are retained in ESRD. Many of these solutes have characteristics, such as protein-binding or sequestration in certain body compartments, which do not allow them to be cleared efficiently through current dialysis methods. It is currently unknown whether these solutes are associated with the poor outcomes experienced by dialysis patients. The overall goal of this application is to identify retained solutes which are associated with poor outcomes in hemodialysis patients. The study design will be a cohort study in which biological specimens have been obtained and stored. These stored specimens will be retrieved, analyzed for levels of putative toxins and correlated with important patient outcomes. We propose to take advantage of the large specimen repositories available in the CHOICE and HEMO studies, as well as the prior work to carefully characterize patients and their outcomes, to test hypotheses that particular kidney failure solutes (e.g. p-cresol sulfate, indoxyl sulfate, methylamine) are associated with poor dialysis outcomes. CHOICE is a prospective cohort study of 767 incident hemodialysis patients recruited from 1995-1998 and HEMO is a prospective, multicenter, randomized clinical trial in which 1846 participants were recruited between 1995 and 2000. Both these studies have specimen banks containing frozen specimens from baseline and annual follow-ups which we propose to assay for organic solutes. We will relate levels of these organic solutes to all-cause mortality, cardiovascular events, loss of appetite, low albumin levels, restless leg symptoms and self reported problems with cognition. The application will build a collaboration of experienced programs in the clinical and laboratory sciences to address a fundamental issue in the science of kidney failure and its treatment. This study will have important implications for understanding the cause of the substantial morbidity and mortality in ESRD patients and the development of future interventions to address these causes, thereby seeking to improve the quality and length of life for ESRD patients. The application will build a collaboration of experienced programs in the clinical and laboratory sciences to address a fundamental issue in the science of kidney failure and its treatment. This study will have important implications for understanding the cause of the substantial morbidity and mortality in chronic kidney disease patients and the development of future interventions to address these causes, thereby seeking to improve the quality and length of life for persons with chronic kidney disease. The proposal will build a collaboration of experienced programs in the clinical and laboratory sciences to address a fundamental issue in the science of kidney failure and its treatment. This study will have important implications for understanding the cause of the substantial morbidity and mortality in chronic kidney disease patients and the development of future interventions to address these causes, thereby seeking to improve the quality and length of life for persons with chronic kidney disease.

描述（由申请人提供）：针对血液透析（最常见的肾脏替代方式）治疗终末期肾脏疾病（ESRD），目前旨在清除尿素。血液透析患者的发病率和死亡率远远超过一般人群。最近的血液临床试验表明，增加的尿素清除率并未导致死亡率提高。除尿素外，还有大量有机溶质保留在ESRD中。这些溶质中的许多具有特征，例如某些身体室中的蛋白质结合或隔离，这些特征不允许通过当前的透析方法有效地清除它们。目前尚不清楚这些溶质是否与透析患者所经历的不良结局有关。该应用的总体目标是识别与血液透析患者结局不佳有关的保留溶质。研究设计将是一项队列研究，其中已经获得并存储了生物标本。将检索这些存储的标本，分析推定毒素的水平，并与重要的患者结局相关。我们建议利用选择和血液研究中可用的大型标本存储库，以及先前的工作，以仔细表征患者及其结果，以检验特定肾衰竭溶质的假设（例如硫酸盐，硫酸磷酸P-硫酸甘蓝，硫酸盐，甲基胺）与不良的透水透视均与不良的透过透析相关。选择是对1995年至1998年招募的767例血液透析患者的一项前瞻性队列研究，Hemo是一项前瞻性的，多中心的随机临床试验，在1995年至2000年间招募了1846年的参与者。这两项研究都在基线和年度后续效果中供应有机溶液，以供应我们的frozen标本。我们将将这些有机溶质的水平与全因死亡率，心血管事件，食欲丧失，低白蛋白水平，不安的腿症状以及自我报告的认知问题联系起来。该应用程序将在临床和实验室科学中建立经验丰富的计划的合作，以解决肾脏衰竭及其治疗科学中的基本问题。这项研究将对ESRD患者的大量发病率和死亡率的原因以及未来干预措施的发展具有重要意义，以解决这些原因，从而寻求改善ESRD患者的寿命和寿命。该应用程序将在临床和实验室科学中建立经验丰富的计划的合作，以解决肾脏衰竭及其治疗科学中的基本问题。这项研究将对理解慢性肾脏疾病患者的大量发病率和死亡率的原因以及未来解决这些原因的干预措施具有重要意义，从而寻求改善患有慢性肾脏疾病患者的质量和寿命。该提案将在临床和实验室科学中建立经验丰富的计划的合作 解决肾脏衰竭及其治疗科学的基本问题。这项研究将具有重要的 理解慢性肾脏疾病中大量发病率和死亡率的原因 患者以及未来解决这些原因的未来干预措施的发展，从而寻求改善 患有慢性肾脏疾病的人的质量和寿命。