Preserving Physical Function in Patients with Kidney Disease

As a co-investigator in this proposal (Albert Einstein College of Medicine, PI: Matthew Abramowitz, MD, MS), I will measure changes in m. vastus lateralis skeletal muscle macrophages (both pro- and anti-inflammatory macrophages), fiber type, cross-sectional area, capillarization, lipid content, collagen/extracellular matrix content, and abundance of tissue resident stem cells, including satellite cells, fibroblasts and fibrogenic/adipogenic progenitor cells in patients with advanced chronic kidney disease and healthy controls in frozen human muscle biopsies shipped to the University of Kentucky from Albert Einstein College of Medicine. We have budgeted for immunohistochemical analyses of muscle cross-sections from approximately 200 biopsies over 5 years. Digital microscopic images, as well as quantification of the images, will be provided to investigators at Albert Einstein College of Medicine quarterly. We will communicate regularly by phone, email and video conferencing, in addition to an annual team meeting where I will travel to Albert Einstein College of Medicine. This component of the proposal enables us to define specific cellular adaptations underlying the skeletal muscle pathology in patients with chronic kidney disease. Identification of these biologic mechanisms is needed to delineate the etiology of skeletal muscle pathophysiology and identify novel therapeutic targets that can be pursued in future proposals.