# Mechanisms of Interventions to Ameliorate Sarcopenia in Chronic Kidney Disease

> **NIH NIH K08** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $130,627

## Abstract

Chronic kidney disease (CKD) affects 20 million Americans and contributes to sarcopenia, which includes
muscle loss (atrophy), muscle weakness and/or reduced mobility. Sarcopenia is clinically important as it
contributes to increased fall risk, morbidity and mortality. Although, the pathophysiology of sarcopenia in CKD
remains unknown, sarcopenia in CKD is likely due to aberrant signaling for muscle metabolism, catabolism,
and regeneration. We propose that central components of these to sarcopenic alterations are impaired
skeletal muscle mitochondria and increased myostatin. The overall goal of this proposal is to test the
hypothesis that exercise or myostatin blocking therapy prevents atrophy, but exercise is needed to improve
skeletal muscle metabolism and function in CKD. This goal will be accomplished through a combination of pre-
clinical experiments using our established model of progressive CKD (the Cy/+ rat), pharmacological and non-
pharmacological interventions. We will assess mitochondrial function using high resolution respirometry,
aerobic capacity via VO2max assessment, muscle strength and fatigue assessed by electrical stimulation and
maximal voluntary grip strength, muscle mass, and overall physical activity levels. The interdisciplinary
mentoring team and I are perfectly positioned to undertake this translational work based on our clinical and
preclinical expertise in CKD, myostatin and skeletal muscle. In aim 1 we will assess the efficacy of moderate
and high intensity AEROBIC exercise in improving skeletal muscle metabolism and aerobic capacity in CKD
rats. In aim 2, we will assess the efficacy of moderate and high intensity RESISTANCE training on skeletal
muscle size and strength in CKD rats. In aim 3 we will assess the efficacy of myostatin blocking therapy
compared to optimal exercise in increasing muscle mass, muscle metabolism and function. The current
proposal will develop a number of skills required to be a successful, independent translational research. While
my long term goal is patient implementation, building a solid basic science skill set will allow for parallel studies
that provide a mechanistic understanding. If these studies show efficacy in benefiting skeletal muscle function
and/or mass, these treatments could be rapidly translated into the clinical setting.

## Key facts

- **NIH application ID:** 9960498
- **Project number:** 5K08DK110429-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Keith G Avin
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $130,627
- **Award type:** 5
- **Project period:** 2016-08-18 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960498

## Citation

> US National Institutes of Health, RePORTER application 9960498, Mechanisms of Interventions to Ameliorate Sarcopenia in Chronic Kidney Disease (5K08DK110429-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9960498. Licensed CC0.

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