Unraveling the ultrafiltration rate--mortality association in dialysis patients

描述（由申请人提供）：美国有超过350，000名维持性每周三次血液透析患者。这些患者的生存率极低，死亡率超过一般人群的10倍以上。先前的研究表明，透析实践中的修改，如更温和的超滤率（UFR）可能会提高生存率。UFR由必须清除的液体量（稳态时等于透析间期体重增加; IDWG）和清除该液体的时间（透析时间长度; DSL）决定，两者均与死亡率相关。本项目旨在阐明DSL和IDWG与死亡率之间的独立关联。一项对全国代表性流行性慢性、每周三次血液透析患者人群的匹配、回顾性队列分析（n= 10，000），随访时间为5年，将用于：1）通过分析IDWG不一致但DSL相同的参与者的配对，估计IDWG与死亡率之间的关联，与DSL无关，以及2）估计DSL与死亡率之间的关联，独立于IDWG，通过分析具有不一致DSL但相同IDWG的配对参与者。已选择匹配的研究设计，以允许在IDWG分析中完全控制DSL，并在DSL分析中完全控制IDWG，从而能够准确估计每种与生存的独立关联。研究结果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。之前没有研究评估患者在每周三次透析的情况下延长DSL以应对容量考虑的意愿。确实存在其他未经测试的IDWG控制方法，包括透析间腹膜透析和可穿戴超滤装置。将开发并验证一种仪器，以评估患者遵守液体/盐限制、采用辅助透析间腹膜透析、利用可穿戴超滤装置和扩展DSL的意愿，作为最大限度减少快速UFR需求的方法。然后，该工具将用于调查从新英格兰终末期肾病网络随机选择的5,000名血液透析门诊患者的态度。响应将为临床实践提供信息，并指导未来的体积缓解研究。 公共卫生相关性：透析患者的死亡率极高。该项目旨在通过检查死亡率与透析时间长度以及死亡率与透析间期体重增加的独立关系来阐明积极的超滤率如何增加死亡率。此外，该项目旨在了解透析患者参与不同容量缓解策略的意愿。研究结果将指导临床实践和未来的研究，确定如何修改透析处方，以提高死亡率。

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. PUBLIC HEALTH RELEVANCE: Dialysis patients experience an extremely high burden of mortality. This project seeks to elucidate how aggressive ultrafiltration rates increase mortality by examining the independent relationships of mortality and dialysis session length and mortality and interdialytic weight gain. Additionally, the project seeks to understand dialysis patient willingness to engage in different volume mitigation strategies. Results will guide clinical practice and future research by identifying ways in which the dialytic prescription can be modified to improve mortality.