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 4 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.
For the past several decades, dialysis has been the prevailing treatment paradigm among advanced chronic kidney disease (CKD) patients who are ineligible for or unlikely to receive kidney transplantation. As dialysis may not offer survival benefit nor improved quality of life among certain dialysis subgroups including elderly and multi-morbid patients, there has been growing interest in conservative dialysis-free management as an alternative patient-centered treatment strategy. In this proposal, we will compare hard outcomes and patient- centered endpoints among patients receiving conservative management vs. dialysis transition, and we will develop clinical prediction models that will identify which patients will most benefit from conservative dialysis- free treatment.
