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An Urban Experience
WSVA7-0447
HILL’S: NEPHROLOGY
MUSCLE MATTERS IN THE GERIATRIC CKD PET: WORKING AGAINST THE CLOCK
D. Hutchinson1
1DVM, DACVN, Newbury, MA USA
In 2010 eight percent of the world’s human population were 65 years of age or older. By 2050 this number is expected to triple to 16% of the world’s population.1 With the growing human geriatric population has come increasing interest in diseases commonly afflicting geriatrics as well as unavoidable age-related syndromes impacting quality of life and ability to live independently. Like humans, pets are also aging and there is increased interest in how to improve their quality and quantity of life. One syndrome speculated to affect all aging individuals (human, canine and otherwise) is sarcopenia, the age- related loss of lean body mass (LBM) in the absence of disease. Sarcopenia encompasses both a loss of muscle mass and function. Furthermore, many geriatrics also suffer from chronic diseases such as chronic kidney disease (CKD) which occurs in 32% of cats 15 years of age or older.2 Such diseases also impact LBM through mechanisms involved in cachexia, which is muscle loss due to disease. Together, sarcopenia and cachexia represent important syndromes impacting quality and quantity of life in much of our geriatric population.
Importance:
Sarcopenia occurs in all aging individuals. In humans, there is loss of 5% of muscle mass per decade of life from the fourth decade onwards, potentially increasing after the age of 65 years.3 The rate of muscle loss in the aging pet population has yet to be investigated
but is likely much higher due to their relatively shorter lifespan. Sarcopenia is a newly emerging area of interest in veterinary medicine; however, it is a topic of extensive research within the human medical field due to impact on quality of life, as well as it’s direct association with morbidity and ability to live independently. Similarly, the veterinary profession has begun to consider the effect
of age-related muscle loss on the quality of life in our patients. This is particularly of interest in pet’s already suffering from muscle loss due to chronic disease such as CKD or congestive heart failure (CHF). Many of these pets have lost significant LBM, impacting their mobility, quality of life, and likely mortality- in humans suffering from disease it has been demonstrated that cachexia is an independent predictor of mortality.4 While yet to be investigated it is likely that cachexia indirectly impacts survival time in pets. Cachexia results in several negative outcomes associated with quality of life, which plays a pivotal role in clients’ choice of euthanasia. Addressing
causes of muscle loss in aging, diseased patients is therefore of great interest. This has led to the creation of Muscle Condition Scoring (MCS) systems for dogs and cats designed for use in medical records. In order to understand how to manage these syndromes,
it is important to first grasp the pathophysiologic mechanisms involved.
Mechanisms:
Sarcopenia and cachexia are both multifactorial syndromes and the underlying mechanisms involved
in each overlap considerably (Figure 1). Muscle mass results from the balance between anabolic and catabolic pathways involved in protein synthesis or breakdown respectively. Both pathways are impacted negatively in cachectic and sarcopenic individuals. Aging as well as chronic disease may result in decreased concentrations, and/or signaling of hormones critical to protein synthesis including insulin-like growth factor-1 (IGF-1) and growth hormone (GH) as well as insulin-resistance. Cachectic individuals also have increased concentrations of cortisol and adrenergic hormones resulting in increased fat oxidation, insulin-resistance and hypermetabolism.5 Inflammatory mediators (e.g., interleukin (IL) -1β, 6, and tumor necrosis factor alpha (TNF-α) through activation of the ubiquitin-proteasome pathway via NF-ҡB-dependent and independent mechanisms) are increased in cachectic individuals and contribute to decreased food intake and protein catabolism. These cytokines also contribute
to insulin-resistance as well as other mechanisms that impact protein synthesis such as inhibition of GH and IGF-1. An observational study in more than 2,000 men and women showed an association between TNF-α and decline in muscle mass and strength.6
Mitochondrial efficiency is also compromised with age and disease and is thought to contribute to decreased muscle mass through a number of mechanisms. Oxidative stress has been well documented in humans suffering from chronic disease and is believed to play
an important role in protein catabolism. In part this may result from stimulation of the ubiquitin-proteosome system and lower activity of antioxidant enzymes including superoxide dismutase and glutathione peroxidase as well as inhibition of protein synthesis.7 Similar mechanisms related to oxidative stress are likely involved in degenerative age-related conditions including sarcopenia as expressed in the Free Radical Theory
on Aging (also known as the Oxidative Stress Theory
of Aging). As outlined above, many factors involved
in cachexia and sarcopenia have been identified in humans and further research is needed to understand any differences that may exist in mechanisms involved in muscle loss in dogs and cats.
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 42ND WORLD SMALL ANIMAL VETERINARY ASSOCIATION CONGRESS AND FECAVA 23RD EUROCONGRESS
  










































































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