Conservative Versus Dialytic Management in Stage V Chronic Kidney Disease

描述(由申请人提供)：本申请涉及广泛的挑战领域“比较有效性研究(05)”具体的挑战主题是“05-AG-104：针对患有多种共存疾病的老年患者的管理策略比较的计划资助和先导研究”这一主题进一步被NIA指定为研究所的最高优先事项。终末期肾病影响了不到0.5%的联邦医疗保险人口，但却占到了联邦医疗保险支出的近7%。尽管负担和费用相当大，但接受透析的患者经历了令人无法接受的高死亡率(每年超过20%)、极高的住院率(每个患者每年住院两次以上，平均每年在医院呆两周)，以及功能状态和与健康相关的生活质量受损。我们和其他人强调了ESRD人群中的高死亡率、发病率、残疾、虚弱和功能受损。肾功能衰竭、其他相关疾病、透析的不完善和并发症在多大程度上导致健康状况不佳尚不清楚。我们建议进行一项初步研究，以测试保守治疗与透析治疗在老年V期慢性肾脏病(CKD)患者中的可行性、安全性和有效性。具体目标是：确定老年(年龄70岁)慢性肾脏病(CKD)V期患者(估计肾小球滤过率(EGFR)为9~1t；15毫升/分钟/1.73m2)与开始透析治疗的可行性；确定V期CKD患者保守治疗与透析治疗的相对安全性；并从健康相关生活质量、晚期CKD的症状和负担、身体功能、体力活动、认知功能、心理健康、营养和炎症状态、身体成分、血压和脉搏波速度、住院率和住院天数等多个方面比较保守治疗和透析治疗对老年V期CKD患者健康和幸福感的相对疗效。这项先导性研究的设计将是一项临床试验，随机分为三个中心(斯坦福大学附属的三个中心)。保守干预将包括仔细关注晚期慢性肾脏疾病的代谢和其他表现，当EGFR持续降至9mL/min/1.73m2以下时，过渡到减量透析处方。透析干预将包括随机开始每周三次血液透析或常规腹膜透析。两组都将每月接受一名调查员、研究护士协调员和肾脏疾病注册营养师专家的研究访问。将对健康状况的许多领域进行评估，并跟踪所有医疗事件。这项研究将主要集中在可行性和安全性上，但也将比较保守和透析管理策略的相对有效性。由于透析是生命维持疗法的象征，这项研究对科学和医疗保健的潜在影响超出了相当大的美国慢性肾脏病V期人群的范围。可以说，由于ESRD对少数群体的影响不成比例，特别是非裔美国人、穷人和没有保险的人，这种类型的比较有效性研究可以影响我们许多最脆弱的公民。我们认为，这项试点试验可能会对医疗保健政策产生重大影响。 公共卫生相关性(由申请人提供)：在没有症状性尿毒症的情况下，晚期慢性肾脏病(CKD)患者可能会也可能不会从开始透析中受益(伴随代谢副产物的血流积累)。这项试点临床试验旨在确定两种替代策略的可行性、安全性和有效性-一种是晚期CKD患者开始透析，另一种是实施一系列保守措施并推迟透析，直到肾功能进一步丧失。如果这项先导试验证明了将患者随机分为这两种方案的可行性，那么这项先导研究的结果可以用来指导设计一项更大规模、更明确的试验。

DESCRIPTION (provided by applicant): This application addresses the broad Challenge Area "Comparative Effectiveness Research (05)" The specific Challenge Topic is "05-AG-104: Planning Grants and Pilot Studies for Comparisons of Management Strategies for Older Patients with Multiple Coexisting Conditions" This topic is further designated by NIA as the Institute's highest priority. End-stage renal disease affects less than 0.5% of the Medicare population, yet accounts for nearly 7% of Medicare expenditures. Despite considerable burden and expense, patients on dialysis experience unacceptably high mortality rates (in excess of 20% per year), exceptionally high rates of hospitalization (more than two hospitalizations per patient per year, spending on average a fortnight per year in hospital), and impaired functional status and health-related quality of life. We and others have highlighted the high rates of mortality, morbidity, disability, frailty and impaired functioning in the ESRD population. The degree to which poor health status results from kidney failure versus other associated diseases versus imperfections and complications of dialysis is unknown. We propose to conduct a pilot study to test the feasibility, safety and efficacy of conservative versus dialytic management in elderly persons with stage V chronic kidney disease (CKD). The Specific Aims are: To determine the feasibility of randomizing elderly (age >70 years) subjects with stage V chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 9 to <15 mL/min/1.73m2) to conservative management versus initiation of dialysis; To determine the relative safety of conservative versus dialytic management for patients with stage V CKD; and To determine the relative efficacy of conservative versus dialytic management for elderly patients with stage V CKD on multiple domains of health and well-being, including: health- related quality of life, symptoms and burden of advanced CKD, physical function, physical activity, cognitive function, mental health, nutritional and inflammatory status, body composition, blood pressure and pulse wave velocity, hospitalization rate and number of hospital days. The design of this pilot study will be a clinical trial, with randomization stratified by center (three centers affiliated with Stanford University. The conservative intervention will include careful attention to metabolic and other manifestations of advanced chronic kidney disease, with a transition to an attenuated dialysis prescription when the eGFR drops consistently below 9 mL/min/1.73m2. The dialytic intervention will include initiation of thrice weekly hemodialysis or conventional peritoneal dialysis following randomization. Both groups will receive monthly study visits with an investigator, research nurse coordinator and registered dietitian expert in kidney disease. Numerous domains of health status will be evaluated, and all medical events will be tracked. The study will focus principally on feasibility and safety, but the relative efficacy of conservative versus dialytic management strategies will also be compared. Since dialysis is emblematic of life-sustaining therapies, the potential impact of this study on science and health care extends beyond the sizable population of Americans with stage V CKD. Arguably, since ESRD disproportionately affects minority populations, particularly African Americans, the poor and the uninsured, this type of comparative effectiveness research can influence many of the most vulnerable of our citizens. We believe that this pilot trial could lead have a significant impact on health care policy. PUBLIC HEALTH RELEVANCE (provided by applicant): Patients with advanced chronic kidney disease (CKD) may or may not benefit from the initiation of dialysis in the absence of symptomatic uremia (accumulation of the bloodstream with by- products of metabolism). This pilot clinical trial aims to determine the feasibility, safety and efficacy of two alternative strategies - one in which patients with advanced CKD begin dialysis, and another in which a series of conservative measures are instituted and dialysis is deferred until there is further loss of kidney function. If this pilot trial demonstrates feasibility in randomizing patients to these two strategies, results from this pilot study can be used to inform the design of a larger, more definitive trial.