Common pathogenetic pathways in the development of sarcopenia in patients with chronic kidney disease and metabolic disorders

Sarcopenia is a syndrome characterized by the progressive and generalized loss of skeletal muscle mass, strength, and physical performance, leading to an increased risk of adverse outcomes, particularly in elderly individuals, including impaired quality of life, disability, and mortality. Chronic kidney disease (CKD) is a condition associated with accelerated aging that contributes to disturbances in nutritional and functional status, thereby predisposing patients, especially whose with end-stage kidney disease, to an increased risk of sarcopenia.

Sarcopenia is considered one of the major geriatric syndromes, while CKD is recognized as an important risk factor for the development of metabolic disturbances and chronic systemic inflammation. The main pathogenetic mechanisms of sarcopenia include mitochondrial dysfunction, age-related degeneration of motor neuron end plates, excessive apoptosis, decreased nitric oxide production, androgen deficiency, reduced activity of satellite and stem cells, systemic inflammation, and glucocorticoid exposure.

CKD is accompanied by multiple metabolic and hormonal abnormalities, including metabolic acidosis, uremia, hyperparathyroidism, and disturbances in increased insulin-like growth factor (IGF) signaling, all of which negatively affect muscle metabolism and increase the risk of sarcopenia. Intestinal dysbiosis is also considered as a potential mechanism contributing to CKD progression, and may indirectly influence muscle.

Several studies have demonstrated an association between loss of muscle mass and deterioration of kidney function, including in patients with sarcopenic obesity. Muscle mass is an important determinant of longevity in the older adults, whereas sarcopenic obesity represent a significant risk factor for adverse health outcomes. However, the prevalence and clinical significance of sarcopenic obesity in patients with CKD remains insufficiently investigated.

Systematic reviews have shown that sarcopenia in CKD patients is associated with multiple adverse clinical outcomes, including falls, fractures, and cardiovascular events. Despite the large number of studies examining these processes, the precise molecular pathways and interactions leading to muscular atrophy remain incompletely understood. Moreover, relatively few systematic reviews and meta-analyses have summarized the prevalence of sarcopenia in CKD, and most available data are limited to dialysis patients and kidney transplant recipients.

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