**3. Protein and energy deficiency and dialysis cachexia**

PEM should be noted among the factors influencing the progression of cardiovascular pathology and the formation of CRS in patients on dialysis [35, 36]. Progressive blood pressure instability with LVH and diastolic dysfunction, acidosis, coronary atherosclerosis, as well as increasing hypoalbuminemia and severe anemia early lead to ineffective HD and loss of residual renal function. These exacerbate hyperhydration with overload and ischemia of myocardial muscle, oxidative stress, and heart chamber dilatation.

The causes of PEM in dialysis patients include protein hypercatabolism with decreased synthesis of albumin and essential amino acids and their subsequent losses (more on PD), L-carnitine deficiency, anorexia with depression, and chronic inflammation with hyperproduction of pro-inflammatory cytokines [37]. Uremic hyperparathyroidism with deficiency of anabolic hormones (insulin, erythropoietin) plays an important role in the PEM development. Progression of PEM is fixed by monitoring of anthropometry (BMI, shoulder muscle circumference, and triceps skinfold), levels of albumin, lymphocytes, TNF-α, transferrin, and CRP.

In the advanced stage of dialysis CRS, PEM progresses to MIA-syndrome (Malnutrtion, Inflammation, Atherosclerosis). This is manifested by ischemic cardiomyopathy provoking arrhythmias, stenotic atherosclerosis with diffuse calcification of arteries and heart valves, and treatment-resistant anemia and hypoalbuminemia [38].

**Dialysis cachexia** in MIA syndrome is formed in BMI under 15 kg/m<sup>2</sup> with hypoalbuminemia (<30 g/l). Clinically it manifests by severe cardiovascular, endocrine, and immune disorders [39]. It is characteristic of the late stage of CRS, when dialysis cachexia is aggravated by cachexia of chronic heart failure (CHF). The formed CHF aggravates PEM because of acidosis with additional hypercatabolism, oxidative stress, impaired absorption syndrome and hypoalbuminemia, and polypragmasia. These patients have poorly controlled hypertension with recurrent intra-dialysis hypotension, ischemic cardiomyopathy with arrhythmias, widespread coronary atherosclerosis and calcinosis, severe hyperparathyroidism, and encephalopathy. There is a high risk of dementia and infection with outcome in bacterial sepsis. Successful treatment of anorexia, hypoalbuminemia, infectious complications, and encephalopathy is possible only with a comprehensive correction of depression, immunodeficiency (anticytokines, antibiotics), anemia, amino acid and L-carnitine deficiency, tube (parenteral) feeding, and infusion of proteins. In severe cachexia, kidney transplantation is effective.
