Unraveling the ultrafiltration rate--mortality association in dialysis patients

描述(申请人提供)：美国有超过350,000名每周三次维持性血液透析患者。这些患者的存活率非常低，死亡率比普通人群高出10倍以上。先前的研究表明，修改透析操作，如更温和的超滤率(UFR)可能会提高存活率。UFR由必须清除的液量(在稳定状态下等于透析间增重；IDWG)和清除液体的时间(透析时间长度；DSL)决定，每一项都可能与死亡率有关。本项目旨在阐明DSL和IDWG与死亡率之间的独立联系。对全国具有代表性的慢性血液透析患者(n=10,000)进行配对的回顾性队列分析，随访时间为5年：1)通过分析IDWG不一致但相同的DSL的配对参与者，估计IDWG与死亡率之间的关系，独立于DSL；2)通过分析DSL不协调但相同的配对参与者，估计DSL与死亡率的关联，独立于IDWG。选择了一项配对研究设计，以便在IDWG分析中完全控制DSL，并在DSL分析中允许IDWG准确估计每个因素与生存的独立关联。这些发现将为临床实践的修改提供信息，并指导未来的研究。除了了解DSL和IDWG与死亡率的独立关系外，该项目还将评估患者是否愿意采取旨在通过有针对性的液体管理操作来改善健康和生存的干预措施。在每周三次透析的背景下，没有先前的研究评估患者是否愿意延长DSL以回应容量的考虑。还有其他未经测试的控制IDWG的方法，包括透析间腹膜透析和可穿戴式超滤装置。将开发和验证一种仪器，以评估患者是否愿意遵守液体/盐限制，采用辅助透析间腹膜透析，使用可穿戴式超滤设备，并扩展DSL作为将快速UFR需求降至最低的方法。然后，该仪器将被用来调查从新英格兰终末期肾脏疾病网络中随机选择的5000名血液透析门诊患者的态度。答复将为临床实践提供信息，并指导未来的容量缓解研究。

DESCRIPTION (provided by applicant): There are over 350,000 maintenance thrice-weekly hemodialysis patients in the United States. These patients have exceptionally poor survival with mortality rates exceeding those of the general population by greater than 10-fold. Prior research has suggested that modifications in dialytic practice such as gentler ultrafiltration rates (UFR) may improve survival. UFR is determined by both the amount of fluid that must be removed (which at steady state equals the inter-dialytic weight gain; IDWG) and the time over which this fluid is removed (dialysis session length; DSL), each of which are plausibly associated with mortality. This project seeks to elucidate the independent associations between DSL and IDWG and mortality. A matched, retrospective cohort analysis of a nationally representative population of prevalent chronic, thrice weekly hemodialysis patients (n= 10,000) with follow-up time of 5 years will be used to: 1) estimate the association between IDWG and mortality, independent of DSL, through analysis of matched pairs of participants with discordant IDWG but identical DSL, and 2) estimate the association between DSL and mortality, independent of IDWG, through analysis of matched pairs of participants with discordant DSL but identical IDWG. A matched study design has been chosen to allow for complete control of DSL in analyses of IDWG and for IDWG in analyses of DSL to enable accurate estimation of the independent association of each with survival. Findings will inform modifications to clinical practice and direct future research. In addition to understanding the independent relationships of DSL and IDWG and mortality, the project will assess patients' willingness to adopt interventions aimed at improving health and survival through targeted manipulations of fluid management. No prior research has assessed patient willingness to extend DSL in response to volume considerations within the context of thrice weekly dialysis. Other untested methods of IDWG control including interdialytic peritoneal dialysis and wearable ultrafiltration devices do exist. An instrument will be developed and validated to assess patient willingness to adhere to fluid/salt restrictions, adopt adjunct interdialytic peritoneal dialysis, utilize wearable ultrafiltration devices, and extend DSL as methods to minimize need for rapid UFR. This instrument will then be used to survey attitudes of 5,000 randomly selected hemodialysis outpatients from the End Stage Renal Disease Network of New England. Responses will inform clinical practice and guide future research in volume mitigation.