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）：使用血液透析（最常见的肾脏替代方式）治疗终末期肾病（ESRD）目前旨在清除尿素。血液透析患者的发病率和死亡率仍然很高，远远超过普通人群。最近的 HEMO 临床试验表明，尿素清除率的提高并不会降低死亡率。除尿素外，还有大量有机溶质保留在 ESRD 中。许多这些溶质具有一些特性，例如蛋白质结合或隔离在某些身体隔室中，这些特性不允许它们通过当前的透析方法有效地清除。目前尚不清楚这些溶质是否与透析患者的不良预后有关。该应用的总体目标是识别与血液透析患者不良预后相关的残留溶质。研究设计将是一项队列研究，其中已获取并储存生物样本。这些储存的样本将被检索、分析假定的毒素水平并与重要的患者结果相关联。我们建议利用 CHOICE 和 HEMO 研究中可用的大型样本存储库以及之前的工作来仔细描述患者及其结果，以测试特定肾衰竭溶质（例如对甲酚硫酸盐、硫酸吲哚酚、甲胺）与不良的透析结果相关。 CHOICE 是一项前瞻性队列研究，招募了 1995 年至 1998 年期间招募的 767 名血液透析患者，而 HEMO 是一项前瞻性、多中心、随机临床试验，在 1995 年至 2000 年间招募了 1846 名参与者。这两项研究的样本库均包含基线和冷冻样本。我们建议对有机溶质进行年度随访。我们将把这些有机溶质的水平与全因死亡率、心血管事件、食欲不振、白蛋白水平低、腿部不安症状和自我报告的认知问题联系起来。该应用程序将建立临床和实验室科学领域经验丰富的项目的合作，以解决肾衰竭及其治疗科学中的基本问题。这项研究对于了解 ESRD 患者高发病率和死亡率的原因以及制定未来干预措施来解决这些原因，从而寻求改善 ESRD 患者的生活质量和寿命具有重要意义。该应用程序将建立临床和实验室科学领域经验丰富的项目的合作，以解决肾衰竭及其治疗科学中的基本问题。这项研究对于了解慢性肾病患者高发病率和死亡率的原因以及制定未来的干预措施来解决这些原因具有重要意义，从而寻求改善慢性肾病患者的生活质量和寿命。该提案将建立临床和实验室科学领域经验丰富的项目的合作，以 解决肾衰竭及其治疗科学中的一个基本问题。这项研究将具有重要意义 对了解慢性肾病发病率和死亡率高的原因的影响 患者和未来干预措施的发展来解决这些原因，从而寻求改善 慢性肾病患者的生活质量和寿命。