Physical Activity and Muscle Strength in Pediatric CKD

PROJECT SUMMARY For youth with chronic kidney disease (CKD), cardiovascular disease (CVD) is a leading cause of morbidity and early mortality. Youth with CKD are less physically active than their healthy peers. They also have lower muscle strength, which may be a proxy for overall physical inactivity or could represent an independent predictor of CVD.

Physical activity is a well-recognized determinant of health and quality of life, but physical activity’s effects on muscle strength may be compromised in CKD. Characterizing the relationships between physical activity, muscle strength and CVD can inform potential therapeutic targets to improve cardiac outcomes. Identification of effective

strategies to increase physical activity, and the extent to which physical activity and muscle strength mitigate CVD complications are major knowledge gaps in pediatric CKD research. Aim 1 will test the efficacy of a 12-week physical activity intervention in 64 adolescents with CKD. Guided by the Multiphase Optimization Strategy (MOST) framework, an optimization trial will identify intervention components

that increase average daily moderate to vigorous physical activity by 15 min/day, a clinically meaningful increase. The components will be grounded in established behavioral change theories and be delivered via Way to Health, a web-based platform, to overcome barriers at the point of clinical care where time and resources are limited.

Aim 2 will leverage existing longitudinal data from the Chronic Kidney Disease in Children Study (CKiD) to determine the extent to which physical activity and muscle strength mitigate CVD complications. This aim will quantify the associations of self-reported physical activity and hand grip strength, a validated proxy of muscle

strength, with early changes in cardiac structure and function: left ventricular hypertrophy and diastolic dysfunction. Left ventricular hypertrophy, defined by an elevated left ventricular mass index, is the most common cardiac abnormality in children with CKD and is the strongest predictor of sudden cardiac events in adults with

CKD. Diastolic dysfunction occurs early in pediatric CKD and associates with death in adults with CKD. These aims will advance knowledge by identifying the optimized digital-based intervention components, specific to youth with CKD, to increase physical activity and by quantifying the impact of physical activity and muscle

strength on CVD. They are responsive to the NIDDK Strategic Plan for Research by utilizing 1) technology to improve access to participants; 2) an innovative trial design; 3) direct participant feedback to engage stakeholders; and 4) data from an existing NIH-funded cohort study. Within the outstanding research

environment of The Children’s Hospital of Philadelphia and the University of Pennsylvania and under the mentorship of Drs. Sandra Amaral, Babette Zemel, and Knashawn Morales, this K23 provides training in longitudinal data analysis, health behavior science, and clinical trial design and analysis, incorporating digitally

based tools. This will launch the PI’s career as a pediatric nephrology researcher with unique expertise in health behavior change and digital-based interventions to improve the health and longevity of youth living with CKD.