True effects of uremic sarcopenia – A study on low comorbidity dialysis patients and healthy controls (DIAGIB)

Abstract

The most important mechanism for protein degradation and muscle wasting on cellular level is the ubiquitin-proteasome system (UPS). This system is activated in a uraemic milieu because of its hormonal changes, metabolic acidosis, low-grade inflammation and insulin resistance, which are associated with a worsening renal function from an early stage. Diabetic uraemic patients have a higher prevalence and more advanced forms of uraemic sarcopenia. Physical inactivity promotes degradation of muscle proteins on a cellular level. On the other hand, the exercise works against muscle wasting also by reducing the low-grade inflammation and correcting the negative hormonal changes. This positive hormonal effect also attenuate the uraemic dysfunction of specific cells in muscle tissue that are responsible for regeneration of muscle cells after injury. Low-grade inflammation is present at an early stage of renal failure, this can be demonstrated by increased levels of (CRP, IL-6 and TNF-a) in the population of uraemic patients. IL-6 and CRP negatively correlate with muscle mass in dialysis patients. Inflammation activates UPS with resulting degradation of proteins; it also inhibits myocyte differentiation through the activation of specific transcription factors. Metabolic acidosis causes increased degradation and reduced synthesis of proteins. Research has shown that supplementation of bicarbonate decreases protein degradation in patients on hemodialysis and peritoneal dialysis. Muscle biopsy of individuals with vitamin D deficiency shows changes similar to the ones found in uraemic sarcopenia, with atrophy of fast twitch Type II muscle fibers. Uraemic patients show a similar prolongation of the relaxation phase of muscle contraction that is seen in vitamin D deficient individuals, independent of serum calcium, phosphorus and PTH. This facts demonstrate a probable role of changes in vitamin D metabolism on the pathogenesis of uraemic sarcopenia. Chronic kidney disease (CKD) affects uraemic sarcopenia also through sex and growth hormones. The level of sex hormones is decreased in both genders, which augments uraemic sarcopenia. Uraemic milieu is linked to a resistance to growth hormone, which increases protein catabolism in muscles. Conclusion Muscle wasting causes lower quality of life and increases morbidity and mortality of CKD patients. Mechanisms of uraemic sarcopenia are complex and especially pronounced in elderly and diabetic, which account for a large proportion of patients with advanced kidney disease. We have to be aware of the early stages of uraemic sarcopenia in CKD patients, when the preventive and therapeutic measures are more effective than in the advanced stages.