Defining Optimal Transitions of Care in Advanced Kidney Disease: Conservative Management vs. Dialysis Approaches

项目摘要/摘要 1972年的联邦医疗保险终末期肾病(ESRD)计划使几乎所有人都能获得透析 为了延长进展为终末期肾病(ESRD)的晚期慢性肾病(CKD)患者的生存时间。每个人 年~美国有120,000名患者过渡到透析，成为主要但昂贵的治疗范例 尿毒症、生化和容量紊乱。然而，在过去的45年里，几乎没有 在开发以患者为中心的治疗方案方面的进展或创新，以超越透析的晚期CKD。 由我们的团队在NIH U01《慢性肾脏病的护理过渡》(TCCKD)美国下领导的开创性研究 肾脏数据系统(USRDS)特殊研究中心显示，过渡到透析与1) 死亡率高，特别是在治疗的第一年，2)经常住院，3)与健康有关的质量差 生活质量(HRQOL)，4)失去独立性，5)功能衰退，6)高戒断日期，特别是在 老年患者和合并疾病患者。这促使人们对保守派的兴趣与日俱增，并迫切需要 作为一种替代治疗选择的非透析管理。然而，这一战略仍然没有得到充分利用，原因是 主要不确定因素涉及：1)保守治疗与透析治疗的疗效比较 硬结果和以患者为中心的终点，以及2)哪些患者将从非透析治疗中受益。 我们的多重PI R01提案将通过使用创新的纵向数据来解决这些知识差距 来源来自美国两个最大的综合医疗系统，即OptomLabs(联合医疗保健)和 国家退伍军人事务部(VA)数据与联邦医疗保险和USRDS资源(2007-18)相关联，并与 在迄今为止关于保守治疗与透析过渡的最大规模的研究中，确定了预期的CKD队列。 使用倾向评分匹配，目标1将检查保守治疗与透析之间的关系 与死亡率和住院率的过渡(共同主要结果)，以及熟练的护理设施安置， 两家大型OptomLabs和VA的重症监护入院人数和医疗成本(次要结果) 队列中每组有50万名晚期CKD患者(EGFR和lt；25ml/min/1.73m2)。在这两个队列中，目标2 将开发临床预后模型，预测患者存活和住院的可能性 保守管理与透析。在116名4-5期CKD患者的前瞻性队列中，Aim 3将 比较保守治疗与透析准备对血管病变纵向轨迹的影响 HRQOL(主要结果)和身体表现/活动、症状和营养(次要结果) 使用严格的程序化数据收集和经过验证的仪器。我们的发现将产生重大影响 关于患者护理和政策，1)为广大的CKD人群扩大以患者为中心的治疗选择，2) 通过确定哪些患者是最佳候选对象，为临床指南生成严格的证据 保守管理，以及3)告知有志于提供非透析治疗的临床实践模型 作为一种符合患者选择的方法，基于美国推进的美国肾脏健康倡议。

PROJECT SUMMARY/ABSTRACT The 1972 Medicare End-Stage Renal Disease (ESRD) program has led to near-universal access to dialysis in order to extend the survival of advanced chronic kidney disease (CKD) patients progressing to ESRD. Each year ~120,000 patients in the US transition to dialysis as the dominant yet costly treatment paradigm for uremic, biochemical, and volume derangements. However, in the past 4½ decades, there has been little progress or innovation in developing patient-centered treatment options for advanced CKD beyond dialysis. Pioneering research led by our team under the NIH U01 “Transitions of Care in CKD” (TCCKD) United States Renal Data System (USRDS) Special Study Center have shown that transition to dialysis is associated with 1) high mortality particularly in the 1st year of treatment, 2) frequent hospitalizations, 3) poor health-related quality of life (HRQOL), 4) loss of independence, 5) functional decline, and 6) high withdrawal dates, particularly in elderly and comorbid patients. This has prompted rising interest and pressing urgency for conservative dialysis-free management as an alternative treatment option. Yet this strategy remains under-utilized due to major uncertainties regarding 1) the comparative effectiveness of conservative management vs. dialysis on hard outcomes and patient-centered endpoints, and 2) which patients will benefit from dialysis-free treatment. Our Multiple-PI R01 proposal will address these knowledge gaps by using innovative longitudinal data sources from two of the largest US integrated healthcare systems, namely OptumLabs (United Healthcare) and national Veterans Affairs (VA) data linked to Medicare and USRDS resources (2007-18), paired with a well- defined prospective CKD cohort in the largest study of conservative management vs. dialysis transition to date. Using propensity score matching, Aim 1 will examine associations of conservative management vs. dialysis transition with mortality and hospitalization (co-primary outcomes), and skilled nursing facility placement, intensive care admissions, and healthcare costs (secondary outcomes) in two large OptumLabs and VA cohorts each with >0.5 million advanced CKD (eGFR <25ml/min/1.73m2) patients. In these two cohorts, Aim 2 will develop clinical prognostic models that predict an individual’s likelihood of survival and hospitalization with conservative management vs. dialysis. In a prospective cohort of 116 stage 4-5 CKD patients, Aim 3 will compare the impact of conservative management vs. dialysis preparation on the longitudinal trajectory of HRQOL (primary outcome) and physical performance/activity, symptoms, and nutrition (secondary outcomes) using rigorous protocolized data collection with validated instruments. Our findings will have substantial impact on patient care and policy by 1) expanding patient-centered treatment options for the vast CKD population, 2) generating rigorous evidence for clinical guidelines by identifying which patients are optimal candidates for conservative management, and 3) informing clinical practice models aspiring to provide dialysis-free treatment as an approach aligned with patient choice based on the US Advancing American Kidney Health Initiative.