Longitudinal Assessment of Skeletal Muscle Physiology in Dialysis Patients



 DESCRIPTION (provided by applicant): Career Development Plan: I have a background in evidence review as well as in epidemiology of Chronic Kidney Disease (CKD) associated musculoskeletal complications, experience in the assessment of physical performance through my work on a study of exercise in end-stage renal disease (ESRD) patients, and experience in designing and analyzing pilot trials in CKD patients to characterize their musculoskeletal health. In this K23 I will prospectively study muscle loss (sarcopenia) in a cohort study in order to identify its clinical indicators and biomarkers in patients new to dialysis. I will perform assessments in a prospective cohort study and augment this hands-on-training with advanced coursework in epidemiology and biostatistics techniques, basic tools for biomarker measurements and clinical trial design. I will attend national meetings on Musculoskeletal Health and Nephrology. I have a multidisciplinary mentoring team made of scientists in musculoskeletal physiology, muscle mass and physical performance assessment, biomarkers and in the conduct of clinical trials in CKD. Dr. Sharon Moe, my primary mentor has an enviable track record of successfully mentoring junior faculty in nephrology and extramural support in translational research in musculoskeletal disease in CKD. Indiana University (IU) has a wealth of resources for research in this field: 1) investigators in the field of musculoskeletal disease i multiple departments and schools 2) specialized graduate level courses and journal clubs, and 3) the availability of high quality equipment and facilities. I have a commitment from the Chairman of the Department to protect 75% of my time for research career. Research Plan Summary: Dialysis patients have significant sarcopenia which is associated with increased hospitalizations and mortality. My global hypothesis is that patients undergoing dialysis have impaired skeletal muscle regeneration that leads to progressive mobility impairment and/or mortality. I define progressive mobility impairment as a decrease in gait speed of 0.1 m/s over 1 year. To test this, I will utilize data from 100 patients enrolled in the IU cohort of an ongoing, multi-center study of incident dialysis patients, called "LUCID". In Aim 1, I will evaluate muscle mass and strength measures that identify the subset of dialysis patients that develop progressive mobility impairment and key covariates and confounders of that relationship. In Aim 2, I will study the relationship between circulating biomarkers of skeletal muscle regeneration and i) sarcopenia and ii) progressive mobility impairment. In Aim 3 I will utilize the entire US LUCID cohort (n=750) and determine whether levels of circulating markers of muscle regeneration increase the ability to predict mortality in incident dialysis patients, when combined with known risk factors. These translational research studies will enhance my understanding of the pathophysiology of sarcopenia and quantify its clinical changes to identify patients that will benefit from future interventional trials, targeting sarcopenia that I plan to conduct. My long ter goal is to improve musculoskeletal health in patients with kidney disease.