Physical Function in Chronic Kidney Disease: Characterizing the Natural History and Relationship to Clinical Outcomes

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Project Summary Functional status is defined by the ability to perform daily physical tasks necessary for independent living and is essential among persons with chronic kidney disease (CKD) for disease self-management, eligibility for kid- ney transplantation, and for ensuring good quality of life. People with CKD at all stages are at increased risk of poor physical functioning that occurs earlier than in the general population. Due to the high prevalence of phys- ical impairments among persons with CKD, the National Kidney Foundation clinical practice guidelines recom- mend regular assessments to identify those with physical limitations with the goal of improving outcomes. De- spite this acknowledgement of the importance of physical function to the health of persons with CKD, there has been limited research in the setting of CKD that would allow evidence-based clinical monitoring. To date, stud- ies in kidney disease populations have been limited by examining physical function at one time point, by evalu- ating relationships only with mortality, and by focusing largely on persons with kidney failure with replacement therapy (KFRT) and older adults. Early detection and intervention to prevent physical limitations and disability may be most effective if implemented during earlier stages of CKD and among younger adults. Risk factors of physical function decline have also been inadequately evaluated in persons with CKD and recommended physical function assessments are not routinely performed in CKD care. We propose to use nearly 20 years of follow up data from the NIDDK-sponsored Chronic Renal Insufficiency Cohort (CRIC) Study that represents diverse populations across the spectrum of CKD stages to enhance our understanding of the prognostic im- portance of physical function over time among persons with CKD, including insights to risk factors of physical function decline, and to build a clinical monitoring tool of physical function. We will characterize the trajectories of physical function along with their associated factors among people with CKD to increase the understanding of the pathways that lead to physical function decline and to identify modifiable factors for intervention develop- ment (Aim 1). We will determine the relationship of longitudinal physical function with onset of KFRT, hospitali- zations, and death (Aim 2). Lastly, we develop a monitoring tool for physical function that could guide treatment and prognostic decisions in CKD clinical practice. We will also test this tool in an external cohort with advanced CKD (Aim 3). Ultimately, the proposed study will increase our understanding of physical function in CKD, in- cluding insights into risk factors for decline, and its relationship to important outcomes; and the work will culmi- nate in a parsimonious set of physical function measures that can be used for clinical monitoring of physical health to inform treatment and prognostic decisions. This information could change how CKD patients are monitored in clinical care, guide patient-centered treatments, and promote broad improvement in physical func- tion for this high-risk population by catalyzing greater awareness and targeted interventions.