The overall goal of this proposal is to foster the development of the candidate as an independent patient-oriented researcher focusing on skeletal muscle pathology associated with chronic kidney disease (CKD) and its functional and metabolic sequelae. The overarching aim of this proposal is to examine how inflammation affects changes in skeletal muscle physiology and physical function in the period surrounding dialysis initiation. The applicant will receive focused mentoring from experts in the study of CKD, muscle physiology, and metabolism and will combine epidemiological and molecular methods to address this question. This study will be the first to prospectively follow patients with advanced kidney disease in a pivotal moment of transition in their care: the initiation of dialysis. We will perform longitudinal measurements of markers of inflammation and important clinical and functional parameters. We will integrate these data with skeletal muscle physiology, and will simultaneously evaluate multiple homeostatic pathways in skeletal muscle in humans.
Our aims are: (1) To define the association of inflammation with changes in skeletal muscle physiology, lean body mass, and physical function in patients with advanced predialysis CKD; and (2) To define the effect of the transition to chronic dialysis on inflammation, skeletal muscle homeostasis, lean body mass, and physical function. No studies in patients with CKD have simultaneously examined muscle wasting at a biochemical, physiologic, and clinical level as we propose. This application includes a rigorous 5 year career development plan that includes an integrated strategy of intensive mentorship, formal training in new research methods for studying human physiology, focused didactic coursework, and participation in research seminars and national scientific meetings. A significant portion of this plan is devoted to mastering new research methods that will enable the primary investigator to establish an independent research program at the intersection of kidney disease, muscle metabolism, and physical function. In summary, this proposal will produce important, clinically relevant data and is intended to generate preliminary data for an R01 application studying the effects of anti-inflammatory therapy on muscle wasting in patients with CKD. Intensive, focused, and interdisciplinary mentoring will foster the candidate's development as an investigator with expertise studying mechanisms of muscle atrophy in concert with clinical outcomes. This research proposal has the potential to improve the care of patients with CKD by leading to future innovations in the prevention and treatment of muscle wasting and functional decline.

Public Health Relevance

This research proposal has the potential to improve the care of patients with CKD by leading to future innovations in the prevention and treatment of muscle wasting and functional decline in individuals with kidney disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK099438-02
Application #
8876670
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2014-07-01
Project End
2019-04-30
Budget Start
2015-05-01
Budget End
2016-04-30
Support Year
2
Fiscal Year
2015
Total Cost
$184,077
Indirect Cost
$13,593
Name
Albert Einstein College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Abramowitz, Matthew K; Hall, Charles B; Amodu, Afolarin et al. (2018) Muscle mass, BMI, and mortality among adults in the United States: A population-based cohort study. PLoS One 13:e0194697
Androga, Lagu; Sharma, Deep; Amodu, Afolarin et al. (2017) Sarcopenia, obesity, and mortality in US adults with and without chronic kidney disease. Kidney Int Rep 2:201-211
Chen, Wei; Abramowitz, Matthew K (2017) Epidemiology of Acid-Base Derangements in CKD. Adv Chronic Kidney Dis 24:280-288
Abramowitz, Matthew K (2017) Bicarbonate Balance and Prescription in ESRD. J Am Soc Nephrol 28:726-734
Abramowitz, Matthew K; Sharma, Deep; Folkert, Vaughn W (2016) Hidden Obesity in Dialysis Patients: Clinical Implications. Semin Dial 29:391-5
Chen, Wei; Melamed, Michal L; Hostetter, Thomas H et al. (2016) Effect of oral sodium bicarbonate on fibroblast growth factor-23 in patients with chronic kidney disease: a pilot study. BMC Nephrol 17:114
Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K et al. (2016) Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010. PLoS One 11:e0153588
Patel, Ravi; Paredes, William; Hall, Charles B et al. (2015) Variability in monthly serum bicarbonate measures in hemodialysis patients: a cohort study. BMC Nephrol 16:214
Sharma, Deep; Hawkins, Meredith; Abramowitz, Matthew K (2014) Association of sarcopenia with eGFR and misclassification of obesity in adults with CKD in the United States. Clin J Am Soc Nephrol 9:2079-88
Abramowitz, Matthew K (2014) Acid-base balance and physical function. Clin J Am Soc Nephrol 9:2030-2