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Pharmacologic therapeutics in sarcopenia with chronic kidney disease
1Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea.
Abstract:
Inflammation, metabolic acidosis, renin-angiotensin system activation, insulin resistance, and impaired perfusion to skeletal muscles, among others, are possible causes of uremic sarcopenia. These conditions induce the activation of the nuclear factor-kappa B and mitogen-activated protein kinase pathways, adenosine triphosphate ubiquitin-proteasome system, and reactive oxygen species system, resulting in protein catabolism. Strategies for the prevention and treatment of sarcopenia in chronic kidney disease (CKD) are aerobic and resistance exercises along with nutritional interventions. Anabolic hormones have shown beneficial effects. Megestrol acetate increased weight, protein catabolic rate, and albumin concentration, and it increased intracellular water component and muscle mass. Vitamin D supplementation showed improvement in physical function, muscle strength, and muscle mass. Correction of metabolic acidosis showed an increase in protein intake, serum albumin levels, body weight, and mid-arm circumference. The kidney- gut-muscle axis indicates that dysbiosis and changes in gut-derived uremic toxins and short-chain fatty acids affect muscle mass, composition, strength, and functional capacity. Biotic supplements, AST-120 administration, hemodiafiltration, and preservation of residual renal function are alleged to reduce uremic toxins, including indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Synbiotics reversed the microbiota change in CKD patients and decreased uremic toxins. AST-120 administration changed the overall gut microbiota composition in CKD. AST-120 prevented IS and PCS tissue accumulation, ameliorated muscle atrophy, improved exercise capacity and mitochondrial biogenesis, restored epithelial tight junction proteins, and reduced plasma endotoxin levels and markers of oxidative stress and inflammation. In a human study, the addition of AST-120 to standard treatment had modest beneficial effects on gait speed change and quality of life.
Insights
Uremic sarcopenia in chronic kidney disease (CKD) stems from inflammation and metabolic issues, leading to muscle loss. Exercise, nutrition, and therapies targeting gut toxins like AST-120 show promise for treatment.
Area of Science:
- Nephrology
- Gerontology
- Metabolism
Background:
- Uremic sarcopenia, a common complication in chronic kidney disease (CKD), is characterized by muscle wasting and weakness.
- Key contributing factors include inflammation, metabolic acidosis, renin-angiotensin system activation, insulin resistance, and impaired muscle perfusion.
- These pathological processes activate signaling pathways (NF-κB, MAPK) and cellular systems (ubiquitin-proteasome, ROS) that promote protein catabolism.
Purpose of the Study:
- To review the causes, prevention, and treatment strategies for sarcopenia in CKD patients.
- To explore the role of the kidney-gut-muscle axis and the impact of uremic toxins on muscle health.
- To evaluate the efficacy of interventions such as exercise, nutritional support, hormonal therapy, and novel toxin-reducing agents.
Main Methods:
- Literature review of studies investigating sarcopenia in CKD.
- Analysis of interventions including aerobic and resistance exercise, nutritional strategies, and pharmacological agents (megestrol acetate, vitamin D).
- Examination of the kidney-gut-muscle axis, focusing on the impact of gut dysbiosis and uremic toxins (IS, PCS) and potential mitigation strategies (synbiotics, AST-120, hemodiafiltration).
Main Results:
- Exercise, nutritional interventions, anabolic hormones (megestrol acetate), vitamin D, and correction of metabolic acidosis have demonstrated benefits for muscle mass, strength, and function in CKD.
- The kidney-gut-muscle axis highlights how gut dysbiosis and uremic toxins negatively affect muscle.
- AST-120 administration showed potential in reducing uremic toxins, ameliorating muscle atrophy, improving exercise capacity, and reducing inflammation and oxidative stress, with modest benefits observed in a human study.
Conclusions:
- Sarcopenia in CKD is multifactorial, involving inflammation, metabolic derangements, and the gut-muscle axis.
- A combination of exercise, nutrition, and targeted therapies to reduce uremic toxins is crucial for managing uremic sarcopenia.
- Emerging strategies like AST-120 show promise in mitigating muscle loss and improving outcomes in CKD patients.
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